Recurrence of FSGS after Kidney Transplantation in Adults:
FSGS recurrence after kidney transplantation is a major risk factor for graft loss.
Aimed to determine the incidence, predictors, and treatment response of recurrent FSGS
in a large cohort of kidney transplant recipient.
Reported rates of recurrence are wide, ranging from 17% to 55%.
Post-Transplant Glomerular Disease (TANGO) study. This international network of
centers, located in three different continents, studies the recurrence of glomerular
disease after kidney transplantation,
Retrospectively collected data of patients with biopsy-proven native kidney FSGS from
15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses
to therapy.
Materials and Methods:
Study Design, Objectives, and Predictors:
A multicenter, retrospective study in patients from 15 kidney transplant centers
participating in the TANGO study in Europe, Brazil, and the United States.
Objective:
Was to determine the incidence of FSGS recurrence after kidney transplantation in
patients with idiopathic FSGS. We also aimed to identify risk factors for FSGS
recurrence.
Patient Selection and Data Collection:
All adults (aged 16 years) who received a kidney transplant between January 2005 and
December 2015 were reviewed by TANGO investigators in the 15 collaborating centers.
Patient with a biopsy-proven native kidney diagnosis of idiopathic FSGS were included.
Results:
Recurrence of FSGS Fifty-seven patients experienced a recurrence of FSGS post-
transplant (32%; 95% CI, 25% to 39%). Most recurrences occurred early after transplant,
with a median time to recurrence of 1.5 months.
FSGS Recurrence and Graft Survival:
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with
recurrence (39%).
FSGS recurrence was associated with a fivefold higher risk of graft loss, mainly because
of the high rate of graft loss in the patients without response to treatment of recurrent
FSG.
Predictors of FSGS Recurrence:
BMI at transplant as well as history of native kidney nephrectomies and white race.
Previous allograft loss owing to FSGS has been described as a risk factor for recurrent
FSGS.
Response to Treatment of Recurrent FSGS:
Plasmapheresis with or without rituximab was the most frequent treatment (61 patients,
81%) and the only one inducing complete remission.
Frequency of plasmapheresis varied from one to three sessions a week, with duration
ranging from 2 weeks to a year. The median number of rituximab doses was two.
FSGS Recurrence and Post-Transplant Complications:
No differences found in incidence of BK or cytomegalovirus viremia, acute rejection
rates, or cancer between patients with or without a recurrence.
Graft Function:
Proteinuria in patients with partial or no remission was higher than in patients with
complete remission.
EGFR of patients with complete remission were comparable to those of patients who did
not experience recurrent.
For patients with a partial or no remission, eGFR was lower and progressively declined.
Study limitations:
its retrospective design, which could have resulted in selection bias.
Adjustment for all potential confounders was not possible.
Selection of patients with FSGS by history and pathology was performed by clinicians in
the participating centers and was not centralized.
Esmat MD
2 years ago
In the absence of secondary causes such as genetic, viral, drug-associated and adaptive FSGS, the term of primary FSGS is utilized. Recurrence rates of FSGS is between 17-55%, and primary or idiopathic form of FSGS recurs more frequently. TANGO study is a retrospective study which examines collected data of patients with biopsy-proven native kidney FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses to therapy. Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. In this study recurrence rate of FSGS was 32% with a subsequent graft loss around 39%. Older age at primary disease onset, native kidney nephrectomies, white race, and lower BMI at transplant to be associated with a higher risk for recurrence. Recurrent FSGS was most often treated with plasmapheresis with or without rituximab, and this regimen resulted in partial or complete remission in 57% of patients. Response to treatment was associated with significantly better outcomes but is attained in only half of the patients.
Summary :
It’s retrospective and multi center study was conducted in pts from 15 centers of transplant to identify the risk factors and incidence of recurrence of FSGS after transplant with idiopathic FSGS and to identify the outcome of the different treatment modalities.
FSGS recurrence rates after transplant are ranging between 17 to 55%in one study but in this study ranging from 25 to 39% .
Graft loss encountered in 39% of pts with recurrence and occur after 7 months after recurrence
Predictors of FSGS Recurrence:
History of nephrectomy of native kidney
BMI at transplant
Age at diagnosis
White race
Previous graft loss
Response of treatment
Plasma exchange with or without rituximab was the most frequent treatment and are associated with complete remission in 21% , partially remission in 36% and 43% showed no response
MICHAEL Farag
2 years ago
Introduction FSGS is one of the leading glomerular causes of kidney failure in adults. Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic forms frequently recur in the graft with a substantial rate of subsequent graft loss; however, it is still difficult to distinguish between them. In this study, retrospectively collected data of patients with biopsy-proven native kidney FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses to therapy. Overall, FSGS recurrence was associated with a fivefold higher risk of graft loss, mainly because of the high rate of graft loss in the patients without response to treatment of recurrent FSGS. Increased intensity of immunosuppression in patients with recurrent FSGS may lead to a higher risk of infectious complications such as BK virus and cytomegalovirus reactivation. Conclusions Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only
half of the cases.
amiri elaf
2 years ago
Please give a summary of this article
* FSGS is one of the leading glomerular causes of kidney failure in adults.
* When no secondary cause genetic, viral, drug-associated, or adaptive can be identified and the patient presents with a clinical history of nephrotic syndrome, FSGS is termed primary or idiopathic.
*The Reported rates of recurrence are wide, ranging from 17% to 55% in smaller studies and from 9% to 15% in registry based.
*This is multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS, the risk factor and to evaluate the effect of different treatments on recurrent FSGS outcomes.
# Patient Selection and Data Collection
All adults patients who received a kidney transplant with a biopsy-proven native kidney diagnosis of idiopathic FSGS were included. Patients with secondary causes of FSGS, as determined by kidney biopsy were excluded.
# Statistical Analyses
Data are shown as percentages for categorical variables, and as medians (IQR) for continuous variables which analyzed by t test, and binary and categorical variables by
chi-squared or Fisher exact test, then confidence intervals around proportions were calculated by Wald testing.
# Results
A total of 11,742 PKT patients ; 253 patients with idiopathic FSGS were included .
59 patients did not meet inclusion criteria and were excluded. 22 of these patients were excluded because their primary kidney
disease did not manifest with nephrotic syndrome , 176 patients with biopsy-proven primary FSGS were included for analysis.
# Recurrence of FSGS
57 patients had recurrence of FSGS (32%).
Most recurrences occurred early after transplant, with a median time to recurrence of 1.5 months.
The incidence of recurrent FSGS differed across geographical regions .
A higher percentage of patients in the recurrence group (9%) had received two prior transplants compared with non recurrent patients.
# FSGS Recurrence and Graft Survival
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
Graft loss was mainly confined to patients who failed to enter remission ( 65%).
FSGS recurrence was associated with a fivefold higher risk of graft loss, mainly because of the high rate of graft loss in the patients without response to treatment of recurrent FSGS. Ten patients died during the follow-up time: seven patients in the non recurrence group (6%) versus three patients (5%) who experienced FSGS recurrence.
# Predictors of FSGS Recurrence
*There is associations between FSGS recurrence and BMI at transplant
*History of native kidney nephrectomies
*White race
*The geographical region was also of importance in multivariable analysis, with centers in Brazil and Europe having lower recurrence rates than in the United States
*Previous Allografts is a risk factor for recurrent FSGS in subsequent allografts.
# Response to Treatment of Recurrent FSGS
*Immunosuppressive treatments varied across the cohort and included steroids, cyclosporine, plasmapheresis, rituximab, cyclophosphamide, and immunoadsorption
*Plasmapheresis with or without rituximab was the most frequent treatment it was associated with complete remission in 13 patients (21%), partial remission in 22 patients (36%), and no response in 26 patients (43%).
*32 patients received both plasma exchange and rituximab, 25 received only plasmapheresis, and 3 only received rituximab, 2 patients with a complete remission experienced a relapse that responded to repeated treatments.
# FSGS Recurrence and Post-Transplant Complications
Higher risk of infectious complications such as BK virus and cytomegalovirus reactivation.
No differences in incidence of BK or cytomegalovirus viremia, acute rejection rates, or cancer between patients with or without a recurrence, or differences in delayed graft function and diabetes.
# Graft Function
*The proteinuria in patients with partial or no remission was higher than in patients with complete
remission .
*eGFRs of patients with complete remission were comparable to those of patients who did not experience recurrent FSGS.
*For patients with a partial or no remission, eGFR was lower and progressively declined, especially in patients without remission.
mai shawky
2 years ago
Summary:
• Recurrence of FSGS after transplantation can occurs early post transplant.
• risk factors for recurrence in adults include : old age of onset, high BMI, history of native nephrectomies.
• Presented with nephrotic range proteinuria.
• Leaving the native kidneys to act as a sponge to adsorb the circulating permeability factors to prevent recurrence.
Alyaa Ali
2 years ago
FSGS is one of the major glomerular causes of renal failure in adults. FSGS recurrence post-transplant is a vital risk factor for graft loss.
FSGS may be primary or secondary (viral,drug associated or adaptive)
as it is rare disease , most studies are based on small sample size , which decrease the power of study or large registry which is limited by mis-classification of glomerular disease,so TANGO study was done to combine both . It is multi-center taken from 15 centers included 11,742 patients undergo kidney transplantation in the period between to 2015 from whom 176 patients underwent analysis as they had biopsy-proven primary FSGS.
TANGO study revealed that 57 out of 176 patients developed FSGS recurrence after transplantation,which occurred early after transplant with a median time to recurrence of 1.5 months. 9% of patients experienced recurrence had received prior transplants. Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).Graft loss was mainly confined to patients who failed to enter remission,with a median time from recurrence to graft loss of 7 months.
according to predictors of recurrence,
the study showed that old age is a risk factor for recurrence, while the previous study showed the opposite and this may be due to different race and ethnicity.
white race and this in agreement with some previous studies.
Nephrectomy of the native kidney.The hypotheses is that the native kidneys left in situ may act as a “sponge” to absorb the potential pathogenic circulating factor, leading to reduction of the free circulating factor that may injure the transplanted kidney,and this finding is in agreement of previous studies.
lower BMI at time of transplant.
previous allograft loss
according to response to treatment. the study showed a lower response to treatment versus previous studies . About 57% of patients have partial or complete remission to treatment(plasmapheresis with or without rituximab) . The non-standardizedtreatment approach could explain that.
Limitation of this study
it is retrospective
selection bias , selection of patients is not centralized , also history taking and biopsy finding
lack of genetic testing in most patients
Balaji Kirushnan
2 years ago
FSGS and its recurrence post renal transplantation has been discussed in this article….
This is a multicenter, retrospective study which was conducted from 15 different kidney transplant centers in 3 different continents namely in Brazil, Europe and United states. It is a retrospective, multicenter study from the 2005 to 2015. The study is analyzed from the TANGO study which is a multicenter investigational study to study post transplant glomerular diseases…
FSGS can be due to primary or secondary causes. Primary causes can be due to genetic causes namely those related to the podocytes protein mutations or can be related abnormal circulating permeability factors. Many cases of primary FSGS are not exactly diagnosed due to absence of genetic testing. Secondary FSGS result from other causes which cause hyperfiltration injury to the glomeruli with morbid obesity being an important cause. An important clinical differentiating feature is presence of nephrotic syndrome at diagnosis for primary FSGS….
In this study they found out that FSGS recurred in about 33% of the post transplant patients and subsequent graft loss in about 39%. :Previous studies were not powered by adequate sample size. This retrospective study included about 11000 odd patients out of which 245 had primary FSGS diagnosis. This cohort describes a higher age of onset of FSGS to predict recurrence as compared to the previous reports of younger age of onset of FSGS to be associated with recurrence….Higher rate of recurrence of FSGS have been reported in united states cohort as compared to Brazil and Europe. Higher rate of recurrence of FSGS have been reported after native kidney nephrectomies. Native kidneys act like a sponge to absorb the so called abnormal permeability factors and leads to FSGS recurrence after nephrectomy. Recurrent FSGS was associated with those with lower BMI in these cohort.
In this cohort the best response to treatment was seen with Plasmaphresis with rituximab with a response about 57%.
Although this was a retrospective analysis, this is the only multicenter study which has given highlights about the FSGS recurrence.
Safi Annour
2 years ago
Recurrence of FSGS after Kidney Transplantation in Adults Please give a summary of this article
This multicenter, retrospective study was conducted in patients from 15 kidney transplant centers to identify the incidence and risk factors of FSGS recurrence in KTRs with idiopathic FSGS and to identify the outcome to different treatment modalities.
The recurrence rates for FSGS post transplant are ranging from 17 to 55% in one study 1. In this retrospective study the recurrence rate of FSGS ranging from 25% to 39% with a median time to recurrence of 1.5 month. The highest rate of recurrence was observed among patients with history of previous transplant. Graft failure was encountered in 15% of patients without recurrence and in 39% of patients with recurrent FSGS. The median time from recurrence to graft loss is 7 months and mainly in patients who didn’t show remission, those with partial remission experienced graft loss after 3.2 and 6.4 years after recurrence. Patients having complete remission didn’t show any kind of graft loss. Predictors of FSGS Recurrence
BMI at transplant.
history of native kidney nephrectomies
age at diagnosis
white race
geographical region ; centers in Brazil and Europe having lower recurrence rates than in the United States
Previous allograft loss
Response to Treatment of Recurrent FSGS
Plasmapheresis with or without rituximab was the most frequent treatment. This modality of therapy was associated with complete remission in 21%, partial remission in 36% and no response to therapy in 43% of patients.
Although not fully assessed, it seemed that young age at presentation and female sex tend to show good response to therapy.
Reference
Senggutuvan P, Cameron JS, Hartley RB, Rigden S, Chantler C, Haycock G, Williams DG, Ogg C, Koffman G: Recurrence of focal segmental glomerulosclerosis in transplanted kidneys: Analysis of incidence and risk factors in 59 allografts. Pediatr Nephrol
4: 21–28, 1990
Fatima AlTaher
2 years ago
FSGS is a main cause of ESRD in patients with glomerular diseases that may be either idiopathic or secondary in origin . Idiopathic FSGS is characterized by high recurrence rate early post transplantation and poor graft survival . This multicenter retrospective study aimed at investigating the predictors of FSGS recurrence in posttransplantation period ,where factors associated with lower recurrence rates included geographical regions as Brazil and Europe revealed lower recurrence compared with US also higher BMI and older age at disease onset , while higher recurrence rats was encountered in retransplant patients and prior native kidney nephrectomy . Graft loss without FSGS recurrence was detected in patients who had no disease remission or partial remission before transplantation compared with patients with diseased remission before transplantation
Recurrent of FSGS posttransplantation was associated with higher rates of graft loss , complications of heavy IS drugs used for its treatment as higher infection rates , cardiovascular complications, diabetes and cancer
Wael Jebur
2 years ago
This article display the details of TANGO study which was conducted across 3 continents with multiple centers in each, to test the recurrence rate , risk factors for recurrence and ,treatment provided and allograft outcome. The criteria to diagnose primary FSGS was stringent to differentiate it from secondary FSGS, the criteria include clinically Nephrotic syndrome , diffuse podocyte foot process fusion and exclusion of other etiologies.
The study spanned over 10 years ,from 2005 to 2015 ,176 patients diagnosed with Chronic Kidney Disease secondary to primary FSGS and underwent kidney transplantation. 57 patients experienced recurrence of FSGS post transplant ,representing 32%.
Most of the recurrent cases occurred early post transplant within few months, median time for recurrence was 1.5 months.
Risk factors for recurrence:
1}Nephrectomy pre-transplantation: which was interpreted by the researchers as it might be secondary to loss of the renal tissue of nephrectomies kidneys that act as a sponge to absorb the circulating factor used to provoke the pathogenesis of FSGS.
from my point of view , I think the correlation with nephrectomy might be explained by the underlying activity of the FSGS, as the indication for nephrectomy is heavy proteinuria pre transplantation which might reflect an active disease inflicting recurrence post transplantation and not merely the lack of sponge effect of nephrectomised kidneys.
2}Non obese FSGS patients are at higher risk of recurrence then obese FSGS patients.
This finding was explained by the probable misdiagnosis of secondary FSGS related to obesity rather that idiopathic FSGS, this might explain the higher recurrence rate in non obese transplant patients. The down side for this interpretation is based on the known fact that secondary FSGS of obesity is usually non nephrotic and would not show the classical histopathological findings of primary FSGS.
3} older age of onset of FSGS predict higher recurrence rate post transplant, might reflect genetically determined FSGS in younger patients.
Regarding the treatment and outcome :
it was variable , but basically including plasma pheresis and Rituximab as the corner stone of management. With variable duration and intensity, resulting in partial or complete remission in 57%.graft loss reported in those patients who failed to attain remission in around 39%.
Manal Malik
2 years ago
Summary of Recurrence of FSGS after kidney transplantation in adult
Introduction:
Primary or secondary FSGS diagnosis remains a challenging especially if ultrastructal evaluation of the kidney biopsy or genetic testing are missing. Because FSGS rare most published studies are limited by small sample size. Recurrence rate ranging from 17 to 55% in smaller study and 9 to 15% in registry based. In this study retrospective data collection of the patients with biopsy proven native kidney. FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence and response to therapy. Material and methods:
Multicenter retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States. The aims of the study are:
· Determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS.
· To identify risk factors for FSGS recurrence.
· To compare clinical outcome of patients with and without recurrent FSGS.
· To evaluate the effect of different treatment on recurrent FSGS outcome.
Patients’ selection and data collection
An adult who received a kidney transplant between 2005 and become 2015 were included in reviewal. Results:
From total of 11742 patients received a kidney transplant between 2005 and 2015, 176 patients with biopsy proven primary FSGS were included for analysis. 57 patients experienced a recurrence of FSGS post-transplant. Graft failure occurred in 18 patients (15%) without recurrence and 22 patients with recurrence 59%. FSGS recurrence was associated with a fivefold higher risk, mainly because of the high rate of graft loss in patients without response to treatment. There is association between FSGS recurrence and BMI at transplant as well as history of native kidney nephrectomies. 45% and 100% of patients who had lose one or two prior allografts respectively, because of recurrent FSGS experienced another recurrence. 57% patients in this study evaluated the response of them to treat of recurrent FSGS for steroid, cyclosporine, plasmapheresis, rituximab, cyclophosphamide, and immunoadsorption.
Plasmapheresis with or without rituximab was associated with complete remission in 13 patients (21%), patrial remission in 22 patients (36%) and no response in 26 patients (43%)
Study revealed there was no difference in incidence of BK or cytomegalovirus, acute rejection rates occurrence between patients with or without a recurrence and no difference in delay graft function or DM. e GFR for patients with a potential or no remission eGFR was lower and progressively declined especially in patients without remission. Discussion:
Recurrence of FSGS in 32% of patients and subsequent graft loss, 39% treatment of recurrent FSGS with plasmapheresis with or without rituximab result in partial or complete remission in 57% of patients.
Result regarding age at diagnosis should be considered with caution. No consensus on how ethnicity affects recurrence. The result of nephrectomy of native kidney has been associated with ahigh risk for recurrence could be due to bias outcome because the incidence of nephrectomy is low and only preformed in severe disease. The association of average lower BMI at time of transplantation associated with recurrent FSGS it is possible some patients with obesity-induced FSGS were misdiagnosed as primary FSGS. Limitations of this study are:
· Retrospective design which could have result in selection bias
· Adjustment for all potential confounder was not possible
· Selection of patients with FSGS by history and pathology by clinician in the participating centers and was not centralized.
· Lack of genetic testing in most patients which patients which might create bias as genetic FSGS usually dose not recurrent after transplantation.
· TANGO study collects large number of biological sample from patients with FSGS which can allow further investigations and expand the biological understanding of this challenge disease.
Mohamad Habli
2 years ago
FSGS is one of the leading glomerular causes of kidney failure in adults. FSGS is either primary or secondary. Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic forms frequently recur in the graft.
This is a multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States, included kidney transplant between January 2005 and December 2015. 176 patients with biopsy-proven primary FSGS were included for analysis. Electron microscopy evaluation of the kidney biopsy was performed and available for 36 patients. Patients with secondary causes of FSGS, as determined by kidney biopsy were excluded.
Results
-FSGS recurrence was seen in 32% with a graft loss of 39% over 5 years.
-In this study, risk factors for recurrence included old age, low BMI, white race, and native kidney nephrectomies.
-Previous allograft loss owing to FSGS has been described as a risk factor for recurrent FSGS in subsequent allografts.
-Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
-Plasmapheresis +/- rituximab was commonly used for the treatment of recurrent FSGS (81%). Plasmapheresis with or without rituximab was associated with complete remission in 13 patients (21%), partial remission in 22 patients (36%).
-Remission (partial or complete) occurred in 57% with better graft survival.
Limitations
Retrospective design
Selection Bias
Low number of patients per center
Lack of genetic testing to identify secondary genetic FSGS
Ahmed Abd El Razek
2 years ago
Introduction
The precise diagnosis for idiopathic and secondary causes remains challenging, particularly if no renal biopsy or genetic testing were available. Idiopathic FSGS rates of recurrence is high ranging from 17% to 55%. The Post-Transplant Glomerular Disease (TANGO) study was established to help in collecting much data regarding predictors, outcomes treatment modalities and other important information for renal transplant diseases.
Materials and Methods
A multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States is carried out with the objective to determine the incidence of FSGS recurrence after kidney transplantation in those with idiopathic FSGS. Also, to identify the proposed risk factors for FSGS recurrence, compare clinical outcomes of patients with and without recurrent FSGS and to evaluate the effect of different treatments on recurrent FSGS outcomes.
Patient Selection and Data Collection
All adults who received a kidney transplant between January 2005 and December 2015 were selected with a biopsy-proven native kidney diagnosis of idiopathic FSGS.
Results
About 11,742 patients who received a kidney transplant between 2005 and 2015 were screened for FSGS. Only 176 patients with biopsy-proven primary FSGS were included for analysis.
Recurrence of FSGS
57 patients had recurrence of FSGS post-transplant about 32%.Most recurrences were early after transplantation. A high percentage of patients in the recurrence group (9%) had received two prior transplants. Body mass index (BMI) of patients with recurrence was lower than of patients without recurrence. More patients with a recurrence had a prior nephrectomy of native kidneys.
FSGS Recurrence and Graft Survival
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%). Graft loss was mainly confined to patients who failed to enter remission (20 out of 31 patients, 65%), with a median time from recurrence to graft loss of 7 months.
Two out of 16 patients (13%) with partial remission had graft loss after 3.2 and 6.4 years after recurrence. FSGS recurrence was accompanied by fivefold higher risk of graft loss.
Predictors of FSGS Recurrence
There are associations between FSGS recurrence and BMI at transplant as well as history of native kidney nephrectomies. Significant variables also included age and race.
There is no association between time to ESKD and recurrent FSGS.
Previous Allografts and Recurrent FSGS
In this study 45% and 100% of patients who had lost one or two prior allografts, respectively, due to recurrent FSGS experienced another recurrence.
Patients who lost a previous graft because of reasons other than recurrent FSGS were associated with a lower incidence of FSGS recurrence in the new allograft (14%).
Response to Treatment of Recurrent FSGS
Treatment options included Immunosuppressive therapy mainly steroids, cyclosporine, plasmapheresis, rituximab, cyclophosphamide, and immunoadsorption.
75 patients had recurrence; 57 patients had FSGS proved renal biopsy pretransplant.
Plasmapheresis with or without rituximab was the most frequent treatment (61 patients, 81%) and they were the only group inducing complete remission in 13 patients about (21%),while 22 patients had partial remission (36%),and there was no response in 26 patients about (43%).
Five patients did not have the chance for any immunosuppressive management further more being in a state of active infection or affected by advanced scarring on renal biopsy.
Thirty-two patients had both plasma exchange and rituximab, 25 did only plasmapheresis while only 3 patients had Rituximab. Among the 13 patients who had complete remission; 2 of them had relapse with fair response to repeated treatments.
There was no association between early FSGS recurrence and response to treatment in patients managed by plasmapheresis with or without rituximab.
An incidence of higher response to treatment was detected in patients who were at younger age and female patients, however owing to the small sized sample this could not be confirmed or assessed.
FSGS Recurrence and Post-Transplant Complications
Higher risk of infectious and complications were associated with the increase intensity of immunosuppression as BK virus and cytomegalovirus reactivation. However, in our study there was no differences in incidence of BK or cytomegalovirus viremia, acute rejection rates, or cancer between patients with or without a recurrence. Even those patients with diabetes or delayed graft function did not show any difference regarding FSGS recurrence and increased complication rates.
Graft Function
Proteinuria in patients with partial or no remission was higher than in patients with complete remission. There were no difference in eGFRs of patients with complete remission and those who had no recurrent FSGS disease at all. Patients with partial or no remission, eGFRs was much lower and declined progressively as predicted.
Discussion
In this study of idiopathic FSGS, recurrence was detected in 32% of patients, with subsequent graft loss in about 39%.
Higher risk for recurrence was observed in these patient groups having older age at primary disease onset, native kidney nephrectomies, white race, and lower BMI at transplant.
The most common management strategy of recurrent FSGS was plasmapheresis with or without rituximab, and it was accompanied by higher values of remission about 57% either partial or complete.
Limitations of most of studies mainly small sample size and poor data quality, have unfavorable impact regarding achieving accurate results.
On the contrast of many previous studies regarding the association of younger age and higher rate of recurrence, this study considers that older age is associated by higher incidence of recurrence unlike previous studies. This controversy may be due to different study populations included in this study.
Only few patients in this study were tested for genetic causes of FSGS; owing to the fact that genetic causes are less likely to recur at older age groups. This result mandates more studies as this step may propose a drawback for this study.
Data from New-Zealand and Australia suggests a higher risk in nonwhite recipients, which confronts other data reported by United States studies proposing that white race is associated with higher tendency for disease recurrence.
Nephrectomy of native kidneys is also associated by an increased risk of disease recurrence, similarly to other previous studies. This may be explained by the theory suggesting that native kidneys left in situ resembles a “sponge” absorbing the remaining potential pathogenic circulating factors causing their reduction preventing further injury of the transplanted kidney.
However, in this study only 7% of patients did nephrectomy presenting a small number which may assist as false data bias. Keeping in mind that nephrectomy was only done in severe disease course.
Among patients having recurrence, group of them were of average or nearly lower BMI at time of transplantation. Only 6 % of patients having a high BMI experience recurrence in this study (with BMI 30 kg/m2 at transplantation.
Yet, there is no official protocol agreed on for the management of recurrent FSGS including the duration of treatment. Irrespective of the regimen, response to treatment was usually associated with better graft survival.
Disadvantages of this study were depending on retrospective data design, different centers approaches, small sample size and finally the lack of genetic testing for FSGS.
So, recommendations for more powerful studies as the TANGO study needs to be carried out in order to validate more biomarkers and achieve more understanding for such disease recurrence challenges.
Zahid Nabi
2 years ago
FSGS recurrence has always been a concern for transplant physicians and patients. The dilemma remains to diagnose idiopathic FSGS as at times it becomes difficult to differentiate primary from secondary FSGS specially if EM facility is not available.
This retrospective, multi center study (TANGO) was done with a aim to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS. They also aimed to identify risk factors for FSGS recurrence, to compare clinical outcomes of patients with and without recurrent FSGS, and to evaluate the effect of different treatments on recurrent FSGS outcomes.
All adults (aged 16 years) who received a kidney transplant between January 2005 and December 2015 were reviewed by TANGO investigators in the 15 collaborating centers.
Patients with a biopsy-proven native kidney di- agnosis of idiopathic FSGS were included. Patients with secondary causes of FSGS, were excluded.
Patients (11742)who received a kidney transplant between 2005 and 2015 were screened for FSGS in four European centers, five Brazilian centers, and five United States centers
253 patients with idiopathic FSGS were included
59 patients did not meet inclusion criteria and were excluded
176 patients with biopsy-proven primary FSGS were included for analysis.
The rate of recurrence was 32% (57 out of 176 patients).
The median time to recurrence was 1.5 months. The risk factors associated with recurrence included white race, increased age at diagnosis, lower BMI, prior history of nephrectomy and prior history of recurrence in previous transplant especially with prior history of 2 transplants.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%)
Graft loss was mainly confined to patients who failed to enter remission.
Ten patients died during the follow-up time: seven patients in the nonrecurrence group (6%) versus three patients (5%) who experienced FSGS recurrence.
Plasmapheresis with or without rituximab was associated with complete remission in 13 patients (21%), partial remission in 22 patients (36%), and no response in 26 patients (43%)
Limitations of study
Retrospective design, which could have resulted in selection bias.
Further, adjustment for all potential confounders was not possible.
Selection of patients with FSGS by history and pathology was performed by clinicians in the participating centers and was not centralized.
Another limitation is the lack of genetic testing in most patients, which might create bias as genetic FSGS usually does not recur after transplantation.
Amit Sharma
2 years ago
Please give a summary of this article
Kidney transplant in patients with basic disease as primary focal segmental glomerulosclerosis (FSGS), one of the most common glomerular cause of renal failure, is associated with high recurrence rates.
The TANGO (Post Transplant Glomerular Disease) project is a multicentre observational cohort study to evaluate recurrence of glomerular disease post-transplant.
The study involved screening transplant recipients between 2005 and 2015 in 14 transplant centers located in Europe, Brazil and United States, with idiopathic FSGS as the basic disease causing renal failure. It aimed to find the recurrence rate and analyse their risk factors, treatments and outcomes. A total of 253 transplant recipients had idiopathic FSGS, out of which 176 were included in the study.
The rate of recurrence was 32% (57 out of 176 patients). The median time to recurrence was 1.5 months. The risk factors associated with recurrence included white race, increased age at diagnosis, lower BMI, prior history of nephrectomy and prior history of recurrence in previous transplant especially with prior history of 2 transplants. The centers in United States had higher recurrence rates. Graft failure was seen in 39% of the recurrent group, mainly in those not achieving remission, increasing the risk by 5 times.
Plasmapheresis with or without rituximab was the most common treatment modality used, and was associated with complete remission in 21% and partial remission in 36% patients, with transplant at a younger age and females showing better responses.
There was no difference with respect to complications like BK virus and CMV infections, as well as risk of malignancies, rejection, diabetes mellitus and delayed graft function on account of FSGS recurrence. eGFR in patients with complete remission was similar to those without recurrence while it was lower in patients with partial or no remission.
Limitations of the study included its retrospective design leading to selection bias, non-centralized selection of patients, all potential confounders were not adjusted, low number of patients per center, lack of genetic testing creating a bias and presence of differences across centers with respect to treatment modalities.
The authors concluded that FSGS recurrence post-transplant happens in one-third of the patients with graft loss risk increasing by 5 times and only 57% show some response to treatment.
Mohamed Fouad
2 years ago
Introduction
FSGS is one of the glomerular diseases that cause kidney failure in children and adults. If there is no secondary cause like genetic, viral, drug-associated, or adaptive can be identified and the patient presents with a clinical history of nephrotic syndrome, FSGS is termed primary or idiopathic. The accurate differentiation between idiopathic and secondary causes remains challenging, particularly if electron microscopy evaluation of the kidney biopsy or genetic testing are not have been done. Differentiation between idiopathic and secondary FSGS is important in patients being prepared for kidney transplantation because idiopathic forms frequently recur in the graft with increased incidence of subsequent graft loss. The documented rates of recurrence are wide, ranging from 17% to 55%.
The study design
This is a multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States. Their primary objective was to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS. As well as to identify risk factors for FSGS recurrence, to compare clinical outcomes of patients with and without recurrent FSGS, and to evaluate the effect of different treatments on recurrent FSGS outcomes.
In conclusion:
-Out of 253 patients included in the study 176 patients with biopsyproven primary FSGS were included for analysis. 57 patients experienced a recurrence of FSGS post-transplant. The median time to recurrence of 1.5 months.
-Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%) , with a median time from recurrence to graft loss of 7 months. Overall, FSGS recurrence was associated with a 5 fold higher risk of graft loss.
-The high rate of graft loss was in the patients without response to treatment of recurrent FSGS (no remissions). There is associations between FSGS recurrence and BMI at transplant as well as history of native kidney nephrectomies.
-Previous allograft loss as a result to FSGS was described as a risk factor for recurrent FSGS in subsequent allografts.
-FSGS Recurrence and Post Transplant Complications due to increased intensity of immunosuppression in patients with recurrent FSGS that may lead to a higher risk of infectious complications such as BK virus and cytomegalovirus reactivation.
-proteinuria in patients with partial or no remission was higher than in patients with complete remission . eGFRs of patients with complete remission were comparable to those of patients who did not experience recurrent FSGS . For patients with a partial or no remission, eGFR was lower and progressively declined.
Ramy Elshahat
2 years ago
The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. Results Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patientsand 39% of them lost their graft over a median of 5 years. A higher risk for recurrence with older age at native kidney disease onset. Other predictors were a white race, body mass index at transplant (HR, 0.89 per kg/m2), and native kidney nephrectomies. Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.
Conclusions
Idiopathic FSGS recurs post-transplant in one-third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
Introduction
FSGS is one of the leading glomerular causes of kidney failure in adults. Diagnosis of 1ry FSGS is difficult and it can be made when no secondary cause (genetic, viral, drug-associated, or adaptive) can be identified and the patient presents with a clinical history of nephrotic syndrome so it remains challenging especially when ultrastructural evaluation of the kidney biopsy or genetic testing is not available. Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic forms frequently recur in the graft.
Exclusion criteria Patients with secondary causes of FSGS, as determined by kidney biopsy (e.g., only mild effacement of foot processes, glomerular hypertrophy) and/or by clinical features (e.g., absent nephrotic syndrome at disease onset or a clear secondary cause, including infections, drugs, reduced kidney mass, long-standing diabetes, or morbid obesity were excluded.
Results Cohort Demographics
Of a total of 11,742 patients who received a kidney transplant between 2005 and 2015 from this group, only 176 patients with biopsy-proven primary FSGS were included for analysis. Patient and donor characteristics of all patients, as well as by recurrence status (recurrent/ nonrecurrent FSGS). Recurrence of FSGS Fifty-seven patients experienced a recurrence of FSGS post-transplant. Most recurrences occurred early after transplant, with a median time to recurrence of 1.5 months. A higher percentage of patients in the recurrence group (9%) had received two prior transplants compared with nonrecurrent patients (P=0.003). Body mass index (BMI) of patients with a recurrence was lower than of patients without a recurrence (2465 kg/m2 versus 2665 kg/m2, respectively; P=0.02)
More patients with a recurrence had a prior nephrectomy of native kidneys.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%). After adjusting for important confounders such as HLA mismatch, pretransplant donor-specific antibody, donor type and age, and post-transplant rejection,
· Patients who didn’t achieve remission Graft loss occurred in 65% with a median time from recurrence to graft loss of 7 months.
· Patients with partial remission Two out of 16 patients (13%) experienced graft loss after 3.2 and 6.4 years after recurrence,
· patients with complete remission did not experience graft loss.
Overall, FSGS recurrence was associated with a fivefold higher risk of graft loss. Predictors of FSGS Recurrence there is regression associations between FSGS recurrence and BMI at transplant as well as the history of native kidney nephrectomies.
Time from native kidney FSGS onset to ESKD was not included in the multivariable model because of 23% of missing data.
Almost 100% of patients who had lost one or two prior allografts because of recurrent FSGS experienced another recurrence. Response to Treatment of Recurrent FSGS was evaluated in 75 patients with FSGS recurrence: Plasmapheresis with or without rituximab was the most frequent treatment (61 patients, 81%) and 13 patients (21%) achieved complete remission, 22 patients (36%) achieved partial remission and 26 patients (43%) achieved no response. The frequency of plasmapheresis varied from one to three sessions a week, with duration ranging from 2 weeks to a year. The median number of rituximab doses was two. Two patients with a complete remission experienced a relapse that responded to repeated treatments. Younger age at transplantation and female sex showed a trend for a higher chance of responding to treatment. nodifferences in the incidence of BK or cytomegalovirus viremia, acute rejection rates, or cancer between patients with or without a recurrence, nor differences in delayed graft function or diabetes.
Sahar elkharraz
2 years ago
This article is multicenter and retrospective study of 15 kidney transplant centres (Tango study 15); from 2005 to 2015; it’s focus on incidence/ risk factors/ outcome of recurrence FSGS post transplant.
FSGS is manifested by nephrotic range proteinuria
It’s may be primary or secondary to infection and drug or obesity or genetic cause
It’s important to differentiate between primary and secondary FSGS because primary FSGS has high rate of recurrence post transplant which ranged between 17% to 55%.
Most references occur early in post transplant within 1.5 months.
Graft failure around 39% of recurrence/ it’s 5 fold higher in recurrence
Risk factors contribute to recurrence
1. High body mass index
2. Younger age groups
3. White race
4. Previous allograft rejection
FSGS associated with obesity because may increase mechanical and metabolic stress and also associated with recurrence post transplant if body mass index more than 30 at time of surgery
Complete remission after patients receive plasma exchange and rituximab
In contrast intensity of immunosuppressive drug may increase risk of infection like BK virus and CMV
Limitations of this study
It’s retrospective study
Select cases not centralised
Most of patients not underwent biopsy especially electron microscopy ( less than 1/3 of patients only do electron microscopy)
Riham Marzouk
2 years ago
30-70% of the primary cases can recur early or late post transplant, genetic type has low rate of recurrence, FSGS recur mostly late secondary to reduced renal mass.
Risk factors for recurrence of FSGS :
1- Young age
2- High BMI
3- White race
4- Rapid progression to ESRD in native kidney
5- Pre transplant severe proteinuria
6- Low serum albumin at the time of diagnosis
7- 80% risk of recurrence in second transplant
Prevention and treatment of recurrent FSGS:
1- Pre transplant plasmapheresis and rituximab is of benefit to prevent recurrence and also used in treatment of recurrence
2- Protocol biopsy is important in early detection.
Nandita Sugumar
2 years ago
Summary
Introduction
This article is about the recurrence of FSGS post kidney transplant in adults. This occurs in one third of the cases and is associated with high risk of graft loss.
When there is no identifiable secondary cause, like infection or drugs, and the patient has a history of nephrotic syndrome, then it is known as FSGS idiopathic or primary.
Finer points to remember :
Idiopathic FSGS is associated with increased risk of graft loss compared to other forms.
Recurrent FSGS is detected by nephrotic range proteinuria post transplant.
It is diagnosed by kidney biopsy which will show FSGS lesions by light microscopy or diffuse foot processes effacement by electron microscopy.
Disease remission is marked by proteinuria below 0.3 g/24 hours with stable eGFR.
Delayed graft function is indicated by need for hemodialysis within the first week post kidney transplant.
There is no consensus about whether age and ethnicity play a significant role in recurrence of FSGS post transplant since there is conflicting data on this.
Native kidney nephrectomy is associated with a high risk of recurrence.
Obesity is a risk factor for secondary FSGS because of increased mechanical and metabolic stress over the glomeruli.
High dose IV cyclosporine has been suggested by some reports, however, the risk of nephrotoxicity in this case remains.
Conclusion :
FSGS can recur as idiopathic or secondary disease post transplant. It is difficult to distinguish between the two especially in obese patients. Patients need to be identified and treated promptly, since there is high risk of graft loss. Patient and graft outcome depend on response to treatment. Treatment can be plasmapheresis with or without rituximab. Using high dose IV cyclosporine is to be done at the disgression of the transplant team, since this measure carries the risk of further nephrotoxicity. Further analysis needs to be done in this area for definitive conclusions on adequate treatment.
Weam Elnazer
2 years ago
Introduction:
FSGS causes renal failure in adults. When no secondary aetiology (genetic, viral, drug-associated, or adaptive) can be found, FSGS is primary or idiopathic. Differentiating between idiopathic and secondary causes is difficult without ultrastructural kidney biopsies or genetic testing.
Patients considering kidney transplantation must distinguish between idiopathic and secondary FSGS because idiopathic forms usually reoccur in the graft, leading to graft loss. Recurrence rates are 17–55%.
Study Design: a multicenter, retrospective study on patients from 15 kidney transplant centres. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. All patients with secondary FSGS (clear secondary aetiology, minor foot process effacement by EM, no nephrotic syndrome, short FU 6 months), were excluded. Results:
-Only 176 of the 11,742 kidney transplant patients who were examined for FSGS and included in the study were found to have a diagnosis of idiopathic FSGS.
-32 per cent of patients had a recurrence of FSGS, with a 95 per cent confidence interval (CI) ranging from 25 per cent to 39 per cent; 57 patients had a recurrence of FSGS, and 39 per cent of those patients lost their graft after a median of 5 years
-The results of a multivariable Cox regression showed that an increased age at the beginning of native kidney disease was associated with an increased risk for recurrence.
–-nephrectomy of native kidneys has been associated with a higher risk for recurrence.
Additional variables were a white race, body mass index at the time of transplant (hazard ratio of 0.89 per kg/m2; 95 per cent confidence interval of 0.83 to 0.95), and native kidney nephrectomies.
-Recurrence patients had a lower BMI at transplant.
The therapies that were used most often were plasmapheresis and rituximab (81 per cent). Remission, either partial or full, was seen in 57% of patients, and this finding was related to improved graft survival.
Limitation:
The retrospective design might have caused selection bias.
Further, not all confounders could be adjusted. Clinicians at participating institutions selected FSGS patients based on history and histology. Although secondary causes and biopsy reports were acquired to decrease variance, centre-to-centre discrepancies may still exist. Less than 1/3 of patients had EM pathology. Missing genetic testing.
Conclusion:
-Plasmapheresis combined with or without rituximab was the primary form of therapy, and a positive response to this treatment was related to improved outcomes in almost half of the patients. One patient out of every three had recurrent idiopathic FSGS, which increased the chance of allograft failure by a factor of five.
Introduction
FSGS is one of glomerular disease that can progress to ESRD, FSGS classified as primary or idiopathic and secondary FSGS due to many causes like autoimmune disease, drugs toxins, infections, reduced nephron mass (adaptive hyperfiltration), obesity. Sometimes difficult to differentiate between primary and secondary FSGS is especially the absent of genetic testing or missing electron microcopy studies. Upon kidney transplantation it’s very important to differentiate primary vs secondary or genetic or inherited type of FSGS, as primary FSGS associated with higher rate of early recurrence post-transplant and can be associated with graft failure with in firt 3 months while secondary FSGS less aggressive and associated with lower rate of relapse with good prognosis . Aim of the study
Tango group study is a large observational multicenter, international study aim to determine the incidence of glomerular disease recurrence post transplantation also to Identify the predictors and treatment response and clinical outcomes of recurrence glomerular diseases including FSGS recurrence post kidney transplantation from 2005-2015. Inclusion criteria: all adults kidney transplant recipients with age of ≥ 16 years old, with biopsy confirmed primary FSGS in native kidneys all data collected retrospectively from the central electronic records Exclusion criteria all recipients with the diagnosis of secondary FSGS ( clear secondary cause , minimal foot process effacement by EM, no evidence of nephrotic syndrome , short FU < 6 months Results
Large cohort study including > 11, 700 cases of kidney transplant recipients with recurrence of idiopathic FSGS was found in 32% (1/3 of cohort). with fivefold increased rate of graft lost over 5 years Follow up intervals (39%).
Combination of plasmapheresis and rituximab was the predominate type of treatment in > 81% of cases with partial and complete response achieved in 57% with better graft survival. Factors predict the increased risk rate of FSGS recurrence include older age at time of transplantation, white race, native kidneys nephrectomies, BMI at time of transplantation . Geographical rate of recurrence was higher rate of FSGS relapse in US population compared to Brazil and Europe. Strength of the study:
Multicenter international cohort with Large sample size of Divers populations (south-American ,US , Europe) and logistically possible and good base for future studies
Long follow-up period for secondary outcome Limitation
Retrospective study with selection bias
no centralization of selection criteria with variation between centers
EM pathology available for 36 cases (Less than 1/3 of cases)which add bias for the selection criteria
missing values for some predictors risk like 23% missing of values for predictors of ESRD outcome.
Genetic testing available for few cases .
conflicting finding regarding some predictors factors may be explained again by bias selection like older age and lower BMI association with higher recurrence rate should be carefully interpreted in this study .
no standardized treatment guideline used for the recurrence FSGS in this cohort including type and duration of treatments used .
.
Introduction
FSGS is one of glomerular disease that can progress to ESRD, FSGS classified as primary or idiopathic and secondary FSGS due to many causes like autoimmune disease, drugs toxins, infections, reduced nephron mass (adaptive hyperfiltration), obesity. Sometimes difficult to differentiate between primary and secondary FSGS is especially the absent of genetic testing or missing electron microcopy studies. Upon kidney transplantation it’s very important to differentiate primary vs secondary or genetic or inherited type of FSGS, as primary FSGS associated with higher rate of early recurrence post-transplant and can be associated with graft failure with in firt 3 months while secondary FSGS less aggressive and associated with lower rate of relapse with good prognosis . Aim of the study
Tango group study is a large observational multicenter, international study aim to determine the incidence of glomerular disease recurrence post transplantation also to Identify the predictors and treatment response and clinical outcomes of recurrence glomerular diseases including FSGS recurrence post kidney transplantation from 2005-2015. Inclusion criteria: all adults kidney transplant recipients with age of ≥ 16 years old, with biopsy confirmed primary FSGS in native kidneys all data collected retrospectively from the central electronic records Exclusion criteria all recipients with the diagnosis of secondary FSGS ( clear secondary cause , minimal foot process effacement by EM, no evidence of nephrotic syndrome , short FU < 6 months Results
Large cohort study including > 11, 700 cases of kidney transplant recipients with recurrence of idiopathic FSGS was found in 32% (1/3 of cohort). with fivefold increased rate of graft lost over 5 years Follow up intervals (39%).
Combination of plasmapheresis and rituximab was the predominate type of treatment in > 81% of cases with partial and complete response achieved in 57% with better graft survival.Factors predict the increased risk rate of FSGS recurrence include older age at time of transplantation, white race, native kidneys nephrectomies, BMI at time of transplantation . Geographical rate of recurrence was higher rate of FSGS relapse in US population compared to Brazil and Europe. Strength of the study:
Multicentral international cohort with Large sample size of Divers populations (south-American ,US , Europe)
Long follow-up period for secondary outcome Limitation
Retrospective study with selection bias
EM pathology available for 36 cases (Less than 1/3 of cases)which add bias for the selection criteria
Big missing values for some predictors risk like 23% missing of values for predictors of ESRD outcome.
genetic testing missing.
FSGS recurrence after kidney transplantation is one of the causes of high risk of the allograft loss
Generally, the course of the disease, risk factors and response to treatments are yet clearly identified
This study was focused to access the incidence, risk factors, and treatment response of the recurrent FSGS
Methodology
This was part of TANGO = The Post-Transplant Glomerular Disease Study; an International, multicenter, observational cohort study to investigate glomerular disease recurrence after transplantation.
Screening for idiopathic FSGS was done between 2005 and 2015
All the data was captured regarding clinical outcomes, treatment, and risk factors
Results
A total of 11,742 patients were ere evaluated for FSGS, 176 had biopsy-proven idiopathic FSGS
FSGS recurrence was seen in 32% with a graft loss of 39% over 5 years
Risk factors for recurrence were; Old age, low BMI, white race, and native kidney nephrectomies
Plasmapheresis +/- rituximab was commonly used for the treatment of recurrent FSGS(81%)
Remission( partial or complete) occurred in 57% with better graft survival
Discussion
Previous studies showed higher recurrent rates of FSGS. This may be due to a small sample size or poor data quality, and no multivariate analysis. They also showed that young age is the risk factor for recurrence contrary to this study. This may be due to differences in the study population and more strict exclusion of secondary FSGS in this study
This study revealed a high risk of recurrent in the white race. This is also contrary to the data from Australia & New Zealand where they showed a high risk of recurrent in non-white races. No consensus on how ethnicity affects FSGS
Native kidney nephrectomy was another risk factor for recurrence. This is because the native may act as spongy and absorb the circulating pathogenic permeability factor and therefore reducing their level
Low BMI was another risk factor for recurrence. This may be probably due to the misdiagnosis of obesity-induced FSGS( mechanical & metabolic stress on the kidney) as a primary FSGS. But still, obese patients are not exempted from recurrent FSGS
Limitation
Retrospective study = selection bias
Differences between centres
Small number of patients/centre
Lack of genetic testing as part of the evaluation of FSGS
Conclusions
Recurrent idiopathic FSGS was seen in one in every three patients with 5 folds risk of allograft loss
The main treatment was plasmapheresis +/- rituximab and response to this treatment were associated with better outcomes in nearly 50% of cases.
Differentiating primary FSGS from secondary is difficult meanwhile it is important to be differentiated because primary FSGS is common to recur after transplantation with subsequent graft loss.
This study collected retrospective data of patients with biopsy-proven FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses to treatment. The results included 176 patients with biopsy-proven primary FSGS, with57% had recurrence of FSGS early post transplant
The patients in the recurrence group had multiple transplants ,and more nephrectomy of native kidney and lower BMI.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
13% of the cases who had partial remission experienced graft loss after 3.2 and 6.4 years after recurrence, whereas ten patients with complete remission did not experience graft loss.
FSGS recurrence cases had fivefold higher risk of graft loss.
FSGS recurrence was correlated with BMI at transplant , age and white race and native kidney nephrectomy .
Centers in Brazil and Europe had lower recurrence rate compared to USA.
Cases who had allograft loss due to etiologies other than recurrent FSGS were associated with a lower incidence of FSGS recurrence in the new allograft.
Plasmapheresis with or without rituximab was given to most of the cases and the only one inducing complete remission.
Increased immunosuppression intensity in cases with recurrent FSGS may lead to a higher risk of infectious complications as BK virus and cytomegalovirus reactivation.
Proteinuria detected in cases without remission or with partial remission was higher than in those with complete remission.
eGFR was progressively decreasing in cases without or with partial remission. Discussion
FSGS recurred in 32% of patients, with subsequent graft loss in 39%.
older age, native kidney nephrectomies, white race, and lower BMI at transplant was accompanied with a higher risk for recurrence. Recurrent FSGS was treated with plasmapheresis with or without rituximab, leading to partial or complete remission in 57% of patients.
Determination of age at diagnosis need to be revaluated
There is no enough data on the effect of ethinicty on recurrence of FSGS.
APOL1-related FSGS is not accompanied with greater risk of recurrence post-transplantation
Nephrectomy of native kidneys incidence is low and is done in severe disease, that can bias outcomes.
Obesity-induced FSGS as a secondary cause can be misdiagnosed as primary FSGS.
Cases were treated with plasmapheresis with or without rituximab Limitations of the study included being retrospective ,lack of unified selection of FSGS cases and adjusting the cofounders and lack of genetic testing.
Introduction Primary, or idiopathic, FSGS frequently recurs after kidney transplantation with an increased rate of the graft loss. Recurrence rates in literature varied depending on the size of studies(17%-55% small studies; 9%-15% in registries). Materials and Methods Study Design TANGO study was a multicenter, retrospective study in 15 renal transplant centers in Europe, Brazil, & the US. All adults who were kidney transplanted from Jan 2005-Dec2015 were reviewed. Objectives The primary objective was to define the incidence of FSGS recurrence post-transplant in idiopathic FSGS. Also the study aimed to assess:
– Risk factors for FSGS recurrence
– Clinical outcomes of recipients with & without recurrent FSGS
– Effect of treatments on recurrent FSGS outcomes. Patients & Data Patients with idiopathic FSGS (biopsy-proven) were included. All patients with secondary causes of FSGS were excluded. Statistical Analyses T test used for continuous variables analysis. Chi-squared or Fisher test for binary & categorical variables. Confidence intervals were calculated by Wald testing. Results Cohorts A total of 11,742 post-kidney transplant patients were screened for FSGS; 253 patients with idiopathic FSGS were included. Finally, 176 patients with biopsy-proven primary FSGS, who fulfilled all criteria, were included for analysis. Recurrence of FSGS Recurrence occurred in 57 patients (32%). Most recurrences were early post-transplant. Median time to recurrence: 1.5 months. FSGS recurrence & graft survival Graft loss seen in 15% without recurrence & in 39% with recurrence. Graft loss was confined to those who failed to remit. Recurrence was associated with a 5-fold increased risk of graft loss. Predictors of higher FSGS recurrence were: Lower BMI at the time of transplantation. Prior native kidney nephrectomy. White race US centers(Brazil & Europe have lower recurrence rates). Prior loss of a graft to FSGS. Older age at disease onset. No association between time to ESRD & recurrent FSGS. Response to Treatment of Recurrent FSGS IS treatments included steroids, cyclosporine, PP, rituximab, cyclophosphamide, & IA. PP (with or without rituximab) was the most frequent treatment, & the only one inducing complete remission. PP with or without rituximab was associated with complete remission in 21%, partial remission in 36%, & no response in 43%. Thirty-two patients received both PP & rituximab, 25 received only PP, & 3 only rituximab. Younger age at transplantation & female sex had a trend for a higher response to treatment. FSGS recurrence & post-transplant complications Incidence of BK or CMV viremia, AR rates, or cancer Was similar between recurrence & non-recurrence patients. No difference in DGF or diabetes between the two groups. Graft Function Proteinuria was higher in those with partial or no remission versus complete remission. eGFR in complete remission patints was similar to those with no recurrent FSGS. In partial or no remission, eGFR was lower & declined progressively. Limitations of the study: It is retrospective one, thus possibility of selection bias. Selection of patients with FSGS was not centralized. The lack of genetic testing in most patients; this causes a bias as genetic FSGS does not recur.
Recurrence of FSGS after Kidney Transplantation in Adults.
Observational(retrospective), multicenter, international cohort study (TANGO)which aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in recipients with biopsy-proven native kidney idiopathic FSGS from 15 centers.
Total number of patients were 11,742 from different centers and 176 patients with biopsy-proven primary FSGS were included for analysis after inclusions and exclusions criteria were established.
Recurrence of FSGS occurred in 57 patients with median time of recurrence 1.5 month.
Risk factors of recurrence are (prior transplantation ,low BMI ,white race ,old age and prior nephrectomy of native kidneys).
Recurrence of FSGS is associated with reduced graft survival, especially in patients with no response to treatment.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
Treatment of recurrent FSS:
Plasmapheresis with or without rituximab was the most frequent treatment (81%) and the only one inducing complete remission which was 21% and partial remission on 36%.
High risk of post-transplant complications were in patients with recurrent FSGS due to immunosuppressive medication.
Graft failure was common in patients with no remission mainly due to residual proteinuria.
Weakness points of the study were :
Bias of selection in retrospective study.
Selection of patients done by local center clinician not by centered one.
Lack of genetic testing to exclude genetic FSGS.
Huda Al-Taee
2 years ago
Summary:
FSGS is a leading cause of ESRD in adults.
It is of 3 types:
primary (idiopathic).
secondary non-genetic (drugs, viruses, adaptive).
secondary genetic form.
Differentiation between primary and secondary forms is essential in patients considered form transplantation as the idiopathic disease tends to recur post-transplant with a possibility of graft loss.
Because FSGS is rare, most of the studies are limited by a small sample size, and the larger registries are missing some data rendering them unreliable for drawing robust conclusions.
So, the TANGO study was established to combine the single-center studies with larger registry data.
Study design:
A multicenter, retrospective study including patients from 15 kidney transplant centers in Europe, Brazil, and the US.
Aim:
To determine the incidence of FSGS recurrence after transplantation in patients with idiopathic FSGS and risk factors for recurrence, compare clinical outcomes of patients with and without recurrent FSGS and evaluate the effect of different treatments on recurrent FSGS outcomes.
Inclusion criteria:
Adults> 16 years who received kidney transplantation between Jan 2005 and Dec 2015.
biopsy-proven native kidney disease of idiopathic FSGS.
Exclusion criteria:
Patients with secondary causes of FSGS are determined by kidney biopsy and/or clinical features.
Patients:
The total number of patients was 11742; 11489 were excluded because they did not have FSGS, so 253 patients with FSGS were studied. Another group of patients were excluded due to either having a secondary cause of FSGS, loss of follow-up, unfit for age inclusion criteria or having no biopsy. Hence, the final number of included patients is 176, 57 had recurrent FSGS, and 119 had not.
Data were extracted from the medical records of all patients included in the study.
EM evaluation of kidney biopsy was available for 36 patients.
Results:
Fifty-seven patients had recurrent FSGS, and 39% lost their graft at around five years post-transplant.
Risk factors for recurrence:
older age at native kidney disease.
white race.
lower BMI at transplant.
native kidney nephrectomy.
previous allograft loss due to recurrent FSGS.
The most frequent treatment, PLEX and rituximab, resulted in partial or complete remission in 57% of patients and were associated with better graft survival.
Limitations:
the retrospective design of the study could have resulted in selection bias.
adjustment for all potential confounders was not possible.
Selection of patients with FSGS by history and pathology was performed by clinicians in the participating centers and was not centralized; differences across center may still be present.
analyses for center variation can not be corrected because the number of patients per center was low and a high number of participating centers.
lack of genetic testing in most patients might create bias as genetic FSGS usually does not recur after transplantation.
Conclusion:
Idiopathic FSGS recurs post-transplant in one-third of the cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
.-FSGS is one of the leading glomerular causes of ESRD in adults .It can be primary or secondary.
-Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic
forms frequently recur in the graft with a substantial rate of subsequent graft loss.
-It is a multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United
States.
– Primary objective was to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS.
-It aimed also to identify risk factors for FSGS recurrence, to compare clinical
outcomes of patients with and without recurrent FSGS, and to evaluate the effect of different treatments on recurrent FSGS outcomes.
-study showed that FSGS recurred in 32% of patients, with subsequent graft loss in 39%.
-Risk for recurrence: older age at primary disease onset, native kidney nephrectomies, white race, and lower BMI at transplant to be associated with a higher
-Recurrent FSGS was most often treated with plasmapheresis with or without rituximab, and this regimen resulted in partial or complete remission in 57%
of patients.
. The fact that older age at onset was a predictor of recurrence may capture
the fact that some cases diagnosed at younger age were, in
fact, genetic and less likely to recur .
-Black (or mixed race) patients, have a higher prevalence of APOL1
high-risk alleles that are associated primarily with FSGS and APOL1-related FSGS is not associated with greater risk of recurrence post-transplantation .
-nephrectomy of native kidneys has been associated with a higher risk for recurrence.
-Response to treatment was associated with graft survival, as graft loss mainly
occurred in patients who failed to enter remission.
– Limitations of study :
1. its retrospectivedesign, which could have resulted in selection bias.
2.Lack of genetic testing in most patients, which might create bias as genetic FSGS usually does not recur after transplantation .
FSGS recurrence post transplant is associated with high risk of graft loss.
The differentiation between idiopathic and secondary FSGS is difficult and challenging. However it is important because idiopathic forms frequently recur post transplant and result in graft loss.
The post transplant glomerular disease (TANGO) study is a large, multicenter, international study use a standardized approach to study recurrence of glomerular disease post transplant.
It is a retrospective study aimed to determine incidence of recurrent FSGS, risk factors for recurrence and the effect of treatment on graft outcome.
It included patients with biopsy proven native kidney diagnosis of idiopathic FSGS and excluded patients with secondary FSGS.
It showed that
FSGS recurred in 32% of patients with subsequent graft loss in 39%
Older age at disease onset, white race, nephrectomy of native kidneys and lower BMI at transplantation were associated with increased risk of recurrence.
treatment with plasmapheresis with or without rituximab resulted in partial or complete remission in 57% of patients.
Response to treatment, irrespective of the regimen used, was associated with graft survival
Graft loss occurred in patients who failed to enter remission.
Limitations:
Retrospective study which may lead to selection bias.
Couldn’t adjust all potential confounders.
Selection of patients with FSGS was not centralized
Genetic testing was not made in most patients.
Focal segmental glomerulosclerosis can recur after kidney transplant and is an important cause of graft loss. It can be primary or secondary due to viral infections, genetic, drug induced or adaptive. Differentiation between two is challenging if ultra structural picture of biopsy and genetic testing is not available. Differentiation between the two is important as idiopathic can recur in graft post transplantation. Data on recurrence is limited to small studies, To address this TANGO ( Post transplant Glomerular disease ) study was established .MethodologyMulticentre retrospective study from 15 transplant centres across Europe , Brazil, United states.. This study included 176 patients with idiopathic FSGS. Primary Objective
To determine the incidence of recurrence of FSGS post transplant in patients with idiopathic FSGS
To identify risk factors of FSGS recurrence
To compare outcome of patients with and without recurrence of FSGS
To evaluate different treatments Results. Risk factors for FSGS.
Old age at onset
Native Nephrectomy
Low BMI at transplant time
White Race
Recurrence Rate of FSGS was 32% Graft loss in 39 % after recurrence of FSGS at 5 years PLEX with and without Rituximab was used as treatment Response rate with PLEX and Ritxuximab -Complete remission in 13 patients-21% Partial remission in 36% and no response in 43%
Limitations
Retrospective design
Selection Bias
Low no of patients per centre
Lack of genetic testing
Excellent Dr Khan This is how to summarise articles. Thank you for your structured writing. Do you agree with the risk factors mentioned in this article?
No Sir
Risk factors for recurrent FSGS
These include :
Onset during childhood
Rapid progression f primary FSGS to ESRD
Recurrent FSGC in previous Graft
Diffuse mesangial hypercellularity
Collapsing variant of FSGS in native kidney
White Race
Reference- Shoji J, Mii A. Terasaki M, Shimizu A. AUpdate on recurrent FSGS in kidney transplantation. Nephron 2020;144(suppl 1):65–70
Ban Mezher
2 years ago
FSGS is an important cause of ESRD adult patients. It classified into primary & secondary ( genetic, viral, drug or adaptive). It is very difficult & important to distinguished between 2 types with out ultrastructural changes in biopsy & genetic test.
TANGO study is an international network of centers ( 3 different countries), it study the recurrence of glomerular disease after renal transplantation with a standardized approach to data & bio sample collection.
Retrospective study include 15 KTx centers aimed to:
identify the incidence of idiopathic FSGS recurrence
identify risk factors of recurrence
compare outcome of patient with FSGS recurrence & non recurrence patients
identify the effect of different treatment strategies on adult outcome of FSGS recurrence
All adult patients who receive renal transplant( Jan 2005-Dec2005) with diagnosis of idiopathic FSGS were included.
Result & discussion:
FSGS recur in 32% with subsequent graft loss in 39%.
risk factors for recurrence were include older age at disease onset, native kidney nephrectomy, white race, & lower BMI at transplant .
Treatment with PE with or without rituximab result in partial or complete remission in 57% of patients
previous studies show wide range of disease recurrence rate due to small size sample which may lead to:
lower precision of incidence estimation & result in broad confidence interval
inflate effect size because of wide distribution so reduce statistical significance
limitation in multiviable analysis
inclusion of multiple transplant per patients
differences in risk factors of recurrence as age of the patients may be due to :
different study population
exclusion of secondary FSGS
ability to perform multivariable analysis in current study
only few patients tested for genetics.
the differences of recurrence related race may be due to APOL1 alleles in black ( 2nd largest risk group in current study)
non standardized treatment protocols may explain low response rate compared to previous studies in addition to bias of these studies.
Limitations of the study:
retrospective design
adjustment for all potential cofoundres was not possible.
selection of patients was not centeralized
inability to correct analysis for center variation
FSGS is classified according to the etiology into:
Primary: due to toxic circulating factor that cause generalized podocyte dysfunction
Secondary: due to hyperfiltration, toxins, viral infection or previous injury
Genetic: due to gene mutation for nephrin (NPHS1) or podocin (NPHS2)
The current study included 176 patients with confirmed idiopathic FSGS and assessed the recurrence rate, graft survival after recurrence, and risk factors associated with recurrence with further evaluation of treatment of recurrent disease
Results
Recurrence rate in patients with primary FSGS in this study was 32% .
Recurrent FSGS is associated with an increased incidence of allograft loss. In the current study, it was found that graft failure occurred 5 years after recurrence in 39% of recipients who develop recurrent primary FSGS
The most common treatment used for recurrent FSGS was plasmapheresis with or without rituximab (81%) with either partial or complete remission occurring in more than half of the patients (57%)
Risk factors for recurrence of primary FSGS in this study was
Age: Patients with disease onset at an older age were more prone to recurrence this is on the contrary to several studies that reported an increase in the incidence of recurrence with disease presentation at a younger age and this may be explained by the probability of including cases with secondary FSGS which occur in older age in the previous studies
Race: White are at increased risk of recurrence than black
Weight: Lower BMI at transplantation is associated with higher recurrence rate as obesity which is a cause of secondary FSGS may presents by picture similar to primary FSGS with nephrotic syndrome
Native nephrectomy in patients with primary FSGS is associated with an increase in the frequency of recurrence of FSGS and this was explained by adsorption of circulating factors by the native kidney
FSGS is one of the leading glomerular causes ESRD. it can be either primary or secondary.
Unfortunately, the primary form is highly recurrent in renal grafts however, the clear distinction between both types is not always possible.
Recurrent FSGS after kidney transplantation is a major risk factor for graft loss. however, the natural history, clinical predictors and response to treatment remain unclear.
This review was an observational multicenter cohort study to determine the incidence, predictors and response to treatment of recurrent FSGS.
The study included 11,742 kidney transplant recipients. 176 patients of them were found as having primary FSGS. recurrence occurred in 57 patients (32%).
The risk factors for recurrence include the following :
1- old age at native kidney disease.
2- white race.
3- BMI.
4- native nephrectomy.
Recurrence of FSGS has a 5-fold higher rate of graft loss.
The available therapies for recurrent FSGS include plasmapharesis, Rituximab, IVIG and other serious therapies.
of course, no. but this is what was mentioned in the article.
Risk factors of recurrent FSGS include the following :
1- onset of FSGS during childhood. 2- rapid progression of primary FSGS to ESRD…. less than 3 years 3- history of recurrent FSGS in previous allograft. 4- diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. 5- Steroid-responsive FSGS in the native kidneys 6- white race patients 7- Pre-transplant bilateral nephrectomy. It is postulated that the native kidneys absorb some permeability factors, although data on nephrectomy are conflicting
Recurrence of FSGS after Kidney Transplantation in Adults:
FSGS recurrence after kidney transplantation is a major risk factor for graft loss.
Aimed to determine the incidence, predictors, and treatment response of recurrent FSGS
in a large cohort of kidney transplant recipient.
Reported rates of recurrence are wide, ranging from 17% to 55%.
Post-Transplant Glomerular Disease (TANGO) study. This international network of
centers, located in three different continents, studies the recurrence of glomerular
disease after kidney transplantation,
Retrospectively collected data of patients with biopsy-proven native kidney FSGS from
15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses
to therapy.
Materials and Methods:
Study Design, Objectives, and Predictors:
A multicenter, retrospective study in patients from 15 kidney transplant centers
participating in the TANGO study in Europe, Brazil, and the United States.
Objective:
Was to determine the incidence of FSGS recurrence after kidney transplantation in
patients with idiopathic FSGS. We also aimed to identify risk factors for FSGS
recurrence.
Patient Selection and Data Collection:
All adults (aged 16 years) who received a kidney transplant between January 2005 and
December 2015 were reviewed by TANGO investigators in the 15 collaborating centers.
Patient with a biopsy-proven native kidney diagnosis of idiopathic FSGS were included.
Results:
Recurrence of FSGS Fifty-seven patients experienced a recurrence of FSGS post-
transplant (32%; 95% CI, 25% to 39%). Most recurrences occurred early after transplant,
with a median time to recurrence of 1.5 months.
FSGS Recurrence and Graft Survival:
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with
recurrence (39%).
FSGS recurrence was associated with a fivefold higher risk of graft loss, mainly because
of the high rate of graft loss in the patients without response to treatment of recurrent
FSG.
Predictors of FSGS Recurrence:
BMI at transplant as well as history of native kidney nephrectomies and white race.
Previous allograft loss owing to FSGS has been described as a risk factor for recurrent
FSGS.
Response to Treatment of Recurrent FSGS:
Plasmapheresis with or without rituximab was the most frequent treatment (61 patients,
81%) and the only one inducing complete remission.
Frequency of plasmapheresis varied from one to three sessions a week, with duration
ranging from 2 weeks to a year. The median number of rituximab doses was two.
FSGS Recurrence and Post-Transplant Complications:
No differences found in incidence of BK or cytomegalovirus viremia, acute rejection
rates, or cancer between patients with or without a recurrence.
Graft Function:
Proteinuria in patients with partial or no remission was higher than in patients with
complete remission.
EGFR of patients with complete remission were comparable to those of patients who did
not experience recurrent.
For patients with a partial or no remission, eGFR was lower and progressively declined.
Study limitations:
its retrospective design, which could have resulted in selection bias.
Adjustment for all potential confounders was not possible.
Selection of patients with FSGS by history and pathology was performed by clinicians in
the participating centers and was not centralized.
In the absence of secondary causes such as genetic, viral, drug-associated and adaptive FSGS, the term of primary FSGS is utilized. Recurrence rates of FSGS is between 17-55%, and primary or idiopathic form of FSGS recurs more frequently.
TANGO study is a retrospective study which examines collected data of patients with biopsy-proven native kidney FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses to therapy. Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. In this study recurrence rate of FSGS was 32% with a subsequent graft loss around 39%.
Older age at primary disease onset, native kidney nephrectomies, white race, and lower BMI at transplant to be associated with a higher risk for recurrence. Recurrent FSGS was most often treated with plasmapheresis with or without rituximab, and this regimen resulted in partial or complete remission in 57% of patients. Response to treatment was associated with significantly better outcomes but is attained in only half of the patients.
Summary :
It’s retrospective and multi center study was conducted in pts from 15 centers of transplant to identify the risk factors and incidence of recurrence of FSGS after transplant with idiopathic FSGS and to identify the outcome of the different treatment modalities.
FSGS recurrence rates after transplant are ranging between 17 to 55%in one study but in this study ranging from 25 to 39% .
Graft loss encountered in 39% of pts with recurrence and occur after 7 months after recurrence
Predictors of FSGS Recurrence:
History of nephrectomy of native kidney
BMI at transplant
Age at diagnosis
White race
Previous graft loss
Response of treatment
Plasma exchange with or without rituximab was the most frequent treatment and are associated with complete remission in 21% , partially remission in 36% and 43% showed no response
Introduction
FSGS is one of the leading glomerular causes of kidney failure in adults. Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic forms frequently recur in the graft with a substantial rate of subsequent graft loss; however, it is still difficult to distinguish between them.
In this study, retrospectively collected data of patients with biopsy-proven native kidney FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses to therapy.
Overall, FSGS recurrence was associated with a fivefold higher risk of graft loss, mainly because of the high rate of graft loss in the patients without response to treatment of
recurrent FSGS.
Increased intensity of immunosuppression in patients with recurrent FSGS may lead to a higher risk of infectious complications such as BK virus and cytomegalovirus reactivation.
Conclusions Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only
half of the cases.
Please give a summary of this article
* FSGS is one of the leading glomerular causes of kidney failure in adults.
* When no secondary cause genetic, viral, drug-associated, or adaptive can be identified and the patient presents with a clinical history of nephrotic syndrome, FSGS is termed primary or idiopathic.
*The Reported rates of recurrence are wide, ranging from 17% to 55% in smaller studies and from 9% to 15% in registry based.
*This is multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS, the risk factor and to evaluate the effect of different treatments on recurrent FSGS outcomes.
# Patient Selection and Data Collection
All adults patients who received a kidney transplant with a biopsy-proven native kidney diagnosis of idiopathic FSGS were included. Patients with secondary causes of FSGS, as determined by kidney biopsy were excluded.
# Statistical Analyses
Data are shown as percentages for categorical variables, and as medians (IQR) for continuous variables which analyzed by t test, and binary and categorical variables by
chi-squared or Fisher exact test, then confidence intervals around proportions were calculated by Wald testing.
# Results
A total of 11,742 PKT patients ; 253 patients with idiopathic FSGS were included .
59 patients did not meet inclusion criteria and were excluded. 22 of these patients were excluded because their primary kidney
disease did not manifest with nephrotic syndrome , 176 patients with biopsy-proven primary FSGS were included for analysis.
# Recurrence of FSGS
57 patients had recurrence of FSGS (32%).
Most recurrences occurred early after transplant, with a median time to recurrence of 1.5 months.
The incidence of recurrent FSGS differed across geographical regions .
A higher percentage of patients in the recurrence group (9%) had received two prior transplants compared with non recurrent patients.
# FSGS Recurrence and Graft Survival
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
Graft loss was mainly confined to patients who failed to enter remission ( 65%).
FSGS recurrence was associated with a fivefold higher risk of graft loss, mainly because of the high rate of graft loss in the patients without response to treatment of recurrent FSGS. Ten patients died during the follow-up time: seven patients in the non recurrence group (6%) versus three patients (5%) who experienced FSGS recurrence.
# Predictors of FSGS Recurrence
*There is associations between FSGS recurrence and BMI at transplant
*History of native kidney nephrectomies
*White race
*The geographical region was also of importance in multivariable analysis, with centers in Brazil and Europe having lower recurrence rates than in the United States
*Previous Allografts is a risk factor for recurrent FSGS in subsequent allografts.
# Response to Treatment of Recurrent FSGS
*Immunosuppressive treatments varied across the cohort and included steroids, cyclosporine, plasmapheresis, rituximab, cyclophosphamide, and immunoadsorption
*Plasmapheresis with or without rituximab was the most frequent treatment it was associated with complete remission in 13 patients (21%), partial remission in 22 patients (36%), and no response in 26 patients (43%).
*32 patients received both plasma exchange and rituximab, 25 received only plasmapheresis, and 3 only received rituximab, 2 patients with a complete remission experienced a relapse that responded to repeated treatments.
# FSGS Recurrence and Post-Transplant Complications
Higher risk of infectious complications such as BK virus and cytomegalovirus reactivation.
No differences in incidence of BK or cytomegalovirus viremia, acute rejection rates, or cancer between patients with or without a recurrence, or differences in delayed graft function and diabetes.
# Graft Function
*The proteinuria in patients with partial or no remission was higher than in patients with complete
remission .
*eGFRs of patients with complete remission were comparable to those of patients who did not experience recurrent FSGS.
*For patients with a partial or no remission, eGFR was lower and progressively declined, especially in patients without remission.
Summary:
• Recurrence of FSGS after transplantation can occurs early post transplant.
• risk factors for recurrence in adults include : old age of onset, high BMI, history of native nephrectomies.
• Presented with nephrotic range proteinuria.
• Leaving the native kidneys to act as a sponge to adsorb the circulating permeability factors to prevent recurrence.
FSGS is one of the major glomerular causes of renal failure in adults. FSGS recurrence post-transplant is a vital risk factor for graft loss.
FSGS may be primary or secondary (viral,drug associated or adaptive)
as it is rare disease , most studies are based on small sample size , which decrease the power of study or large registry which is limited by mis-classification of glomerular disease,so TANGO study was done to combine both . It is multi-center taken from 15 centers included 11,742 patients undergo kidney transplantation in the period between to 2015 from whom 176 patients underwent analysis as they had biopsy-proven primary FSGS.
TANGO study revealed that 57 out of 176 patients developed FSGS recurrence after transplantation,which occurred early after transplant with a median time to recurrence of 1.5 months. 9% of patients experienced recurrence had received prior transplants. Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).Graft loss was mainly confined to patients who failed to enter remission,with a median time from recurrence to graft loss of 7 months.
according to predictors of recurrence,
according to response to treatment. the study showed a lower response to treatment versus previous studies . About 57% of patients have partial or complete remission to treatment(plasmapheresis with or without rituximab) . The non-standardizedtreatment approach could explain that.
Limitation of this study
FSGS and its recurrence post renal transplantation has been discussed in this article….
This is a multicenter, retrospective study which was conducted from 15 different kidney transplant centers in 3 different continents namely in Brazil, Europe and United states. It is a retrospective, multicenter study from the 2005 to 2015. The study is analyzed from the TANGO study which is a multicenter investigational study to study post transplant glomerular diseases…
FSGS can be due to primary or secondary causes. Primary causes can be due to genetic causes namely those related to the podocytes protein mutations or can be related abnormal circulating permeability factors. Many cases of primary FSGS are not exactly diagnosed due to absence of genetic testing. Secondary FSGS result from other causes which cause hyperfiltration injury to the glomeruli with morbid obesity being an important cause. An important clinical differentiating feature is presence of nephrotic syndrome at diagnosis for primary FSGS….
In this study they found out that FSGS recurred in about 33% of the post transplant patients and subsequent graft loss in about 39%. :Previous studies were not powered by adequate sample size. This retrospective study included about 11000 odd patients out of which 245 had primary FSGS diagnosis. This cohort describes a higher age of onset of FSGS to predict recurrence as compared to the previous reports of younger age of onset of FSGS to be associated with recurrence….Higher rate of recurrence of FSGS have been reported in united states cohort as compared to Brazil and Europe. Higher rate of recurrence of FSGS have been reported after native kidney nephrectomies. Native kidneys act like a sponge to absorb the so called abnormal permeability factors and leads to FSGS recurrence after nephrectomy. Recurrent FSGS was associated with those with lower BMI in these cohort.
In this cohort the best response to treatment was seen with Plasmaphresis with rituximab with a response about 57%.
Although this was a retrospective analysis, this is the only multicenter study which has given highlights about the FSGS recurrence.
Recurrence of FSGS after Kidney Transplantation in Adults
Please give a summary of this article
This multicenter, retrospective study was conducted in patients from 15 kidney transplant centers to identify the incidence and risk factors of FSGS recurrence in KTRs with idiopathic FSGS and to identify the outcome to different treatment modalities.
The recurrence rates for FSGS post transplant are ranging from 17 to 55% in one study 1. In this retrospective study the recurrence rate of FSGS ranging from 25% to 39% with a median time to recurrence of 1.5 month. The highest rate of recurrence was observed among patients with history of previous transplant. Graft failure was encountered in 15% of patients without recurrence and in 39% of patients with recurrent FSGS. The median time from recurrence to graft loss is 7 months and mainly in patients who didn’t show remission, those with partial remission experienced graft loss after 3.2 and 6.4 years after recurrence. Patients having complete remission didn’t show any kind of graft loss.
Predictors of FSGS Recurrence
Response to Treatment of Recurrent FSGS
Reference
FSGS is a main cause of ESRD in patients with glomerular diseases that may be either idiopathic or secondary in origin . Idiopathic FSGS is characterized by high recurrence rate early post transplantation and poor graft survival . This multicenter retrospective study aimed at investigating the predictors of FSGS recurrence in posttransplantation period ,where factors associated with lower recurrence rates included geographical regions as Brazil and Europe revealed lower recurrence compared with US also higher BMI and older age at disease onset , while higher recurrence rats was encountered in retransplant patients and prior native kidney nephrectomy . Graft loss without FSGS recurrence was detected in patients who had no disease remission or partial remission before transplantation compared with patients with diseased remission before transplantation
Recurrent of FSGS posttransplantation was associated with higher rates of graft loss , complications of heavy IS drugs used for its treatment as higher infection rates , cardiovascular complications, diabetes and cancer
This article display the details of TANGO study which was conducted across 3 continents with multiple centers in each, to test the recurrence rate , risk factors for recurrence and ,treatment provided and allograft outcome. The criteria to diagnose primary FSGS was stringent to differentiate it from secondary FSGS, the criteria include clinically Nephrotic syndrome , diffuse podocyte foot process fusion and exclusion of other etiologies.
The study spanned over 10 years ,from 2005 to 2015 ,176 patients diagnosed with Chronic Kidney Disease secondary to primary FSGS and underwent kidney transplantation. 57 patients experienced recurrence of FSGS post transplant ,representing 32%.
Most of the recurrent cases occurred early post transplant within few months, median time for recurrence was 1.5 months.
Risk factors for recurrence:
1}Nephrectomy pre-transplantation: which was interpreted by the researchers as it might be secondary to loss of the renal tissue of nephrectomies kidneys that act as a sponge to absorb the circulating factor used to provoke the pathogenesis of FSGS.
from my point of view , I think the correlation with nephrectomy might be explained by the underlying activity of the FSGS, as the indication for nephrectomy is heavy proteinuria pre transplantation which might reflect an active disease inflicting recurrence post transplantation and not merely the lack of sponge effect of nephrectomised kidneys.
2}Non obese FSGS patients are at higher risk of recurrence then obese FSGS patients.
This finding was explained by the probable misdiagnosis of secondary FSGS related to obesity rather that idiopathic FSGS, this might explain the higher recurrence rate in non obese transplant patients. The down side for this interpretation is based on the known fact that secondary FSGS of obesity is usually non nephrotic and would not show the classical histopathological findings of primary FSGS.
3} older age of onset of FSGS predict higher recurrence rate post transplant, might reflect genetically determined FSGS in younger patients.
Regarding the treatment and outcome :
it was variable , but basically including plasma pheresis and Rituximab as the corner stone of management. With variable duration and intensity, resulting in partial or complete remission in 57%.graft loss reported in those patients who failed to attain remission in around 39%.
Summary of Recurrence of FSGS after kidney transplantation in adult
Introduction:
Primary or secondary FSGS diagnosis remains a challenging especially if ultrastructal evaluation of the kidney biopsy or genetic testing are missing. Because FSGS rare most published studies are limited by small sample size. Recurrence rate ranging from 17 to 55% in smaller study and 9 to 15% in registry based. In this study retrospective data collection of the patients with biopsy proven native kidney. FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence and response to therapy.
Material and methods:
Multicenter retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States. The aims of the study are:
· Determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS.
· To identify risk factors for FSGS recurrence.
· To compare clinical outcome of patients with and without recurrent FSGS.
· To evaluate the effect of different treatment on recurrent FSGS outcome.
Patients’ selection and data collection
An adult who received a kidney transplant between 2005 and become 2015 were included in reviewal.
Results:
From total of 11742 patients received a kidney transplant between 2005 and 2015, 176 patients with biopsy proven primary FSGS were included for analysis. 57 patients experienced a recurrence of FSGS post-transplant. Graft failure occurred in 18 patients (15%) without recurrence and 22 patients with recurrence 59%. FSGS recurrence was associated with a fivefold higher risk, mainly because of the high rate of graft loss in patients without response to treatment. There is association between FSGS recurrence and BMI at transplant as well as history of native kidney nephrectomies. 45% and 100% of patients who had lose one or two prior allografts respectively, because of recurrent FSGS experienced another recurrence. 57% patients in this study evaluated the response of them to treat of recurrent FSGS for steroid, cyclosporine, plasmapheresis, rituximab, cyclophosphamide, and immunoadsorption.
Plasmapheresis with or without rituximab was associated with complete remission in 13 patients (21%), patrial remission in 22 patients (36%) and no response in 26 patients (43%)
Study revealed there was no difference in incidence of BK or cytomegalovirus, acute rejection rates occurrence between patients with or without a recurrence and no difference in delay graft function or DM. e GFR for patients with a potential or no remission eGFR was lower and progressively declined especially in patients without remission.
Discussion:
Recurrence of FSGS in 32% of patients and subsequent graft loss, 39% treatment of recurrent FSGS with plasmapheresis with or without rituximab result in partial or complete remission in 57% of patients.
Result regarding age at diagnosis should be considered with caution. No consensus on how ethnicity affects recurrence. The result of nephrectomy of native kidney has been associated with ahigh risk for recurrence could be due to bias outcome because the incidence of nephrectomy is low and only preformed in severe disease. The association of average lower BMI at time of transplantation associated with recurrent FSGS it is possible some patients with obesity-induced FSGS were misdiagnosed as primary FSGS. Limitations of this study are:
· Retrospective design which could have result in selection bias
· Adjustment for all potential confounder was not possible
· Selection of patients with FSGS by history and pathology by clinician in the participating centers and was not centralized.
· Lack of genetic testing in most patients which patients which might create bias as genetic FSGS usually dose not recurrent after transplantation.
· TANGO study collects large number of biological sample from patients with FSGS which can allow further investigations and expand the biological understanding of this challenge disease.
FSGS is one of the leading glomerular causes of kidney failure in adults. FSGS is either primary or secondary. Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic forms frequently recur in the graft.
This is a multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States, included kidney transplant between January 2005 and December 2015. 176 patients with biopsy-proven primary FSGS were included for analysis. Electron microscopy evaluation of the kidney biopsy was performed and available for 36 patients. Patients with secondary causes of FSGS, as determined by kidney biopsy were excluded.
Results
-FSGS recurrence was seen in 32% with a graft loss of 39% over 5 years.
-In this study, risk factors for recurrence included old age, low BMI, white race, and native kidney nephrectomies.
-Previous allograft loss owing to FSGS has been described as a risk factor for recurrent FSGS in subsequent allografts.
-Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
-Plasmapheresis +/- rituximab was commonly used for the treatment of recurrent FSGS (81%). Plasmapheresis with or without rituximab was associated with complete remission in 13 patients (21%), partial remission in 22 patients (36%).
-Remission (partial or complete) occurred in 57% with better graft survival.
Limitations
Retrospective design
Selection Bias
Low number of patients per center
Lack of genetic testing to identify secondary genetic FSGS
Introduction
The precise diagnosis for idiopathic and secondary causes remains challenging, particularly if no renal biopsy or genetic testing were available. Idiopathic FSGS rates of recurrence is high ranging from 17% to 55%. The Post-Transplant Glomerular Disease (TANGO) study was established to help in collecting much data regarding predictors, outcomes treatment modalities and other important information for renal transplant diseases.
Materials and Methods
A multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States is carried out with the objective to determine the incidence of FSGS recurrence after kidney transplantation in those with idiopathic FSGS. Also, to identify the proposed risk factors for FSGS recurrence, compare clinical outcomes of patients with and without recurrent FSGS and to evaluate the effect of different treatments on recurrent FSGS outcomes.
Patient Selection and Data Collection
All adults who received a kidney transplant between January 2005 and December 2015 were selected with a biopsy-proven native kidney diagnosis of idiopathic FSGS.
Results
About 11,742 patients who received a kidney transplant between 2005 and 2015 were screened for FSGS. Only 176 patients with biopsy-proven primary FSGS were included for analysis.
Recurrence of FSGS
57 patients had recurrence of FSGS post-transplant about 32%.Most recurrences were early after transplantation. A high percentage of patients in the recurrence group (9%) had received two prior transplants. Body mass index (BMI) of patients with recurrence was lower than of patients without recurrence. More patients with a recurrence had a prior nephrectomy of native kidneys.
FSGS Recurrence and Graft Survival
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%). Graft loss was mainly confined to patients who failed to enter remission (20 out of 31 patients, 65%), with a median time from recurrence to graft loss of 7 months.
Two out of 16 patients (13%) with partial remission had graft loss after 3.2 and 6.4 years after recurrence. FSGS recurrence was accompanied by fivefold higher risk of graft loss.
Predictors of FSGS Recurrence
There are associations between FSGS recurrence and BMI at transplant as well as history of native kidney nephrectomies. Significant variables also included age and race.
There is no association between time to ESKD and recurrent FSGS.
Previous Allografts and Recurrent FSGS
In this study 45% and 100% of patients who had lost one or two prior allografts, respectively, due to recurrent FSGS experienced another recurrence.
Patients who lost a previous graft because of reasons other than recurrent FSGS were associated with a lower incidence of FSGS recurrence in the new allograft (14%).
Response to Treatment of Recurrent FSGS
Treatment options included Immunosuppressive therapy mainly steroids, cyclosporine, plasmapheresis, rituximab, cyclophosphamide, and immunoadsorption.
75 patients had recurrence; 57 patients had FSGS proved renal biopsy pretransplant.
Plasmapheresis with or without rituximab was the most frequent treatment (61 patients, 81%) and they were the only group inducing complete remission in 13 patients about (21%),while 22 patients had partial remission (36%),and there was no response in 26 patients about (43%).
Five patients did not have the chance for any immunosuppressive management further more being in a state of active infection or affected by advanced scarring on renal biopsy.
Thirty-two patients had both plasma exchange and rituximab, 25 did only plasmapheresis while only 3 patients had Rituximab. Among the 13 patients who had complete remission; 2 of them had relapse with fair response to repeated treatments.
There was no association between early FSGS recurrence and response to treatment in patients managed by plasmapheresis with or without rituximab.
An incidence of higher response to treatment was detected in patients who were at younger age and female patients, however owing to the small sized sample this could not be confirmed or assessed.
FSGS Recurrence and Post-Transplant Complications
Higher risk of infectious and complications were associated with the increase intensity of immunosuppression as BK virus and cytomegalovirus reactivation. However, in our study there was no differences in incidence of BK or cytomegalovirus viremia, acute rejection rates, or cancer between patients with or without a recurrence. Even those patients with diabetes or delayed graft function did not show any difference regarding FSGS recurrence and increased complication rates.
Graft Function
Proteinuria in patients with partial or no remission was higher than in patients with complete remission. There were no difference in eGFRs of patients with complete remission and those who had no recurrent FSGS disease at all. Patients with partial or no remission, eGFRs was much lower and declined progressively as predicted.
Discussion
In this study of idiopathic FSGS, recurrence was detected in 32% of patients, with subsequent graft loss in about 39%.
Higher risk for recurrence was observed in these patient groups having older age at primary disease onset, native kidney nephrectomies, white race, and lower BMI at transplant.
The most common management strategy of recurrent FSGS was plasmapheresis with or without rituximab, and it was accompanied by higher values of remission about 57% either partial or complete.
Limitations of most of studies mainly small sample size and poor data quality, have unfavorable impact regarding achieving accurate results.
On the contrast of many previous studies regarding the association of younger age and higher rate of recurrence, this study considers that older age is associated by higher incidence of recurrence unlike previous studies. This controversy may be due to different study populations included in this study.
Only few patients in this study were tested for genetic causes of FSGS; owing to the fact that genetic causes are less likely to recur at older age groups. This result mandates more studies as this step may propose a drawback for this study.
Data from New-Zealand and Australia suggests a higher risk in nonwhite recipients, which confronts other data reported by United States studies proposing that white race is associated with higher tendency for disease recurrence.
Nephrectomy of native kidneys is also associated by an increased risk of disease recurrence, similarly to other previous studies. This may be explained by the theory suggesting that native kidneys left in situ resembles a “sponge” absorbing the remaining potential pathogenic circulating factors causing their reduction preventing further injury of the transplanted kidney.
However, in this study only 7% of patients did nephrectomy presenting a small number which may assist as false data bias. Keeping in mind that nephrectomy was only done in severe disease course.
Among patients having recurrence, group of them were of average or nearly lower BMI at time of transplantation. Only 6 % of patients having a high BMI experience recurrence in this study (with BMI 30 kg/m2 at transplantation.
Yet, there is no official protocol agreed on for the management of recurrent FSGS including the duration of treatment. Irrespective of the regimen, response to treatment was usually associated with better graft survival.
Disadvantages of this study were depending on retrospective data design, different centers approaches, small sample size and finally the lack of genetic testing for FSGS.
So, recommendations for more powerful studies as the TANGO study needs to be carried out in order to validate more biomarkers and achieve more understanding for such disease recurrence challenges.
FSGS recurrence has always been a concern for transplant physicians and patients. The dilemma remains to diagnose idiopathic FSGS as at times it becomes difficult to differentiate primary from secondary FSGS specially if EM facility is not available.
This retrospective, multi center study (TANGO) was done with a aim to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS. They also aimed to identify risk factors for FSGS recurrence, to compare clinical outcomes of patients with and without recurrent FSGS, and to evaluate the effect of different treatments on recurrent FSGS outcomes.
All adults (aged 16 years) who received a kidney transplant between January 2005 and December 2015 were reviewed by TANGO investigators in the 15 collaborating centers.
Patients with a biopsy-proven native kidney di- agnosis of idiopathic FSGS were included. Patients with secondary causes of FSGS, were excluded.
Patients (11742)who received a kidney transplant between 2005 and 2015 were screened for FSGS in four European centers, five Brazilian centers, and five United States centers
253 patients with idiopathic FSGS were included
59 patients did not meet inclusion criteria and were excluded
176 patients with biopsy-proven primary FSGS were included for analysis.
The rate of recurrence was 32% (57 out of 176 patients).
The median time to recurrence was 1.5 months. The risk factors associated with recurrence included white race, increased age at diagnosis, lower BMI, prior history of nephrectomy and prior history of recurrence in previous transplant especially with prior history of 2 transplants.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%)
Graft loss was mainly confined to patients who failed to enter remission.
Ten patients died during the follow-up time: seven patients in the nonrecurrence group (6%) versus three patients (5%) who experienced FSGS recurrence.
Plasmapheresis with or without rituximab was associated with complete remission in 13 patients (21%), partial remission in 22 patients (36%), and no response in 26 patients (43%)
Limitations of study
Retrospective design, which could have resulted in selection bias.
Further, adjustment for all potential confounders was not possible.
Selection of patients with FSGS by history and pathology was performed by clinicians in the participating centers and was not centralized.
Another limitation is the lack of genetic testing in most patients, which might create bias as genetic FSGS usually does not recur after transplantation.
Kidney transplant in patients with basic disease as primary focal segmental glomerulosclerosis (FSGS), one of the most common glomerular cause of renal failure, is associated with high recurrence rates.
The TANGO (Post Transplant Glomerular Disease) project is a multicentre observational cohort study to evaluate recurrence of glomerular disease post-transplant.
The study involved screening transplant recipients between 2005 and 2015 in 14 transplant centers located in Europe, Brazil and United States, with idiopathic FSGS as the basic disease causing renal failure. It aimed to find the recurrence rate and analyse their risk factors, treatments and outcomes. A total of 253 transplant recipients had idiopathic FSGS, out of which 176 were included in the study.
The rate of recurrence was 32% (57 out of 176 patients). The median time to recurrence was 1.5 months. The risk factors associated with recurrence included white race, increased age at diagnosis, lower BMI, prior history of nephrectomy and prior history of recurrence in previous transplant especially with prior history of 2 transplants. The centers in United States had higher recurrence rates. Graft failure was seen in 39% of the recurrent group, mainly in those not achieving remission, increasing the risk by 5 times.
Plasmapheresis with or without rituximab was the most common treatment modality used, and was associated with complete remission in 21% and partial remission in 36% patients, with transplant at a younger age and females showing better responses.
There was no difference with respect to complications like BK virus and CMV infections, as well as risk of malignancies, rejection, diabetes mellitus and delayed graft function on account of FSGS recurrence. eGFR in patients with complete remission was similar to those without recurrence while it was lower in patients with partial or no remission.
Limitations of the study included its retrospective design leading to selection bias, non-centralized selection of patients, all potential confounders were not adjusted, low number of patients per center, lack of genetic testing creating a bias and presence of differences across centers with respect to treatment modalities.
The authors concluded that FSGS recurrence post-transplant happens in one-third of the patients with graft loss risk increasing by 5 times and only 57% show some response to treatment.
Introduction
FSGS is one of the glomerular diseases that cause kidney failure in children and adults. If there is no secondary cause like genetic, viral, drug-associated, or adaptive can be identified and the patient presents with a clinical history of nephrotic syndrome, FSGS is termed primary or idiopathic. The accurate differentiation between idiopathic and secondary causes remains challenging, particularly if electron microscopy evaluation of the kidney biopsy or genetic testing are not have been done. Differentiation between idiopathic and secondary FSGS is important in patients being prepared for kidney transplantation because idiopathic forms frequently recur in the graft with increased incidence of subsequent graft loss. The documented rates of recurrence are wide, ranging from 17% to 55%.
The study design
This is a multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United States. Their primary objective was to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS. As well as to identify risk factors for FSGS recurrence, to compare clinical outcomes of patients with and without recurrent FSGS, and to evaluate the effect of different treatments on recurrent FSGS outcomes.
In conclusion:
-Out of 253 patients included in the study 176 patients with biopsyproven primary FSGS were included for analysis. 57 patients experienced a recurrence of FSGS post-transplant. The median time to recurrence of 1.5 months.
-Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%) , with a median time from recurrence to graft loss of 7 months. Overall, FSGS recurrence was associated with a 5 fold higher risk of graft loss.
-The high rate of graft loss was in the patients without response to treatment of recurrent FSGS (no remissions). There is associations between FSGS recurrence and BMI at transplant as well as history of native kidney nephrectomies.
-Previous allograft loss as a result to FSGS was described as a risk factor for recurrent FSGS in subsequent allografts.
-FSGS Recurrence and Post Transplant Complications due to increased intensity of immunosuppression in patients with recurrent FSGS that may lead to a higher risk of infectious complications such as BK virus and cytomegalovirus reactivation.
-proteinuria in patients with partial or no remission was higher than in patients with complete remission . eGFRs of patients with complete remission were comparable to those of patients who did not experience recurrent FSGS . For patients with a partial or no remission, eGFR was lower and progressively declined.
The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. Results Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients and 39% of them lost their graft over a median of 5 years. A higher risk for recurrence with older age at native kidney disease onset. Other predictors were a white race, body mass index at transplant (HR, 0.89 per kg/m2), and native kidney nephrectomies. Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.
Conclusions
Idiopathic FSGS recurs post-transplant in one-third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
Introduction
FSGS is one of the leading glomerular causes of kidney failure in adults. Diagnosis of 1ry FSGS is difficult and it can be made when no secondary cause (genetic, viral, drug-associated, or adaptive) can be identified and the patient presents with a clinical history of nephrotic syndrome so it remains challenging especially when ultrastructural evaluation of the kidney biopsy or genetic testing is not available. Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic forms frequently recur in the graft.
Exclusion criteria Patients with secondary causes of FSGS, as determined by kidney biopsy (e.g., only mild effacement of foot processes, glomerular hypertrophy) and/or by clinical features (e.g., absent nephrotic syndrome at disease onset or a clear secondary cause, including infections, drugs, reduced kidney mass, long-standing diabetes, or morbid obesity were excluded.
Results Cohort Demographics
Of a total of 11,742 patients who received a kidney transplant between 2005 and 2015 from this group, only 176 patients with biopsy-proven primary FSGS were included for analysis. Patient and donor characteristics of all patients, as well as by recurrence status (recurrent/ nonrecurrent FSGS). Recurrence of FSGS Fifty-seven patients experienced a recurrence of FSGS post-transplant. Most recurrences occurred early after transplant, with a median time to recurrence of 1.5 months. A higher percentage of patients in the recurrence group (9%) had received two prior transplants compared with nonrecurrent patients (P=0.003). Body mass index (BMI) of patients with a recurrence was lower than of patients without a recurrence (2465 kg/m2 versus 2665 kg/m2, respectively; P=0.02)
More patients with a recurrence had a prior nephrectomy of native kidneys.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%). After adjusting for important confounders such as HLA mismatch, pretransplant donor-specific antibody, donor type and age, and post-transplant rejection,
· Patients who didn’t achieve remission Graft loss occurred in 65% with a median time from recurrence to graft loss of 7 months.
· Patients with partial remission Two out of 16 patients (13%) experienced graft loss after 3.2 and 6.4 years after recurrence,
· patients with complete remission did not experience graft loss.
Overall, FSGS recurrence was associated with a fivefold higher risk of graft loss.
Predictors of FSGS Recurrence there is regression associations between FSGS recurrence and BMI at transplant as well as the history of native kidney nephrectomies.
Time from native kidney FSGS onset to ESKD was not included in the multivariable model because of 23% of missing data.
Almost 100% of patients who had lost one or two prior allografts because of recurrent FSGS experienced another recurrence. Response to Treatment of Recurrent FSGS was evaluated in 75 patients with FSGS recurrence: Plasmapheresis with or without rituximab was the most frequent treatment (61 patients, 81%) and 13 patients (21%) achieved complete remission, 22 patients (36%) achieved partial remission and 26 patients (43%) achieved no response. The frequency of plasmapheresis varied from one to three sessions a week, with duration ranging from 2 weeks to a year. The median number of rituximab doses was two. Two patients with a complete remission experienced a relapse that responded to repeated treatments. Younger age at transplantation and female sex showed a trend for a higher chance of responding to treatment. no differences in the incidence of BK or cytomegalovirus viremia, acute rejection rates, or cancer between patients with or without a recurrence, nor differences in delayed graft function or diabetes.
This article is multicenter and retrospective study of 15 kidney transplant centres (Tango study 15); from 2005 to 2015; it’s focus on incidence/ risk factors/ outcome of recurrence FSGS post transplant.
FSGS is manifested by nephrotic range proteinuria
It’s may be primary or secondary to infection and drug or obesity or genetic cause
It’s important to differentiate between primary and secondary FSGS because primary FSGS has high rate of recurrence post transplant which ranged between 17% to 55%.
Most references occur early in post transplant within 1.5 months.
Graft failure around 39% of recurrence/ it’s 5 fold higher in recurrence
Risk factors contribute to recurrence
1. High body mass index
2. Younger age groups
3. White race
4. Previous allograft rejection
FSGS associated with obesity because may increase mechanical and metabolic stress and also associated with recurrence post transplant if body mass index more than 30 at time of surgery
Complete remission after patients receive plasma exchange and rituximab
In contrast intensity of immunosuppressive drug may increase risk of infection like BK virus and CMV
Limitations of this study
It’s retrospective study
Select cases not centralised
Most of patients not underwent biopsy especially electron microscopy ( less than 1/3 of patients only do electron microscopy)
30-70% of the primary cases can recur early or late post transplant, genetic type has low rate of recurrence, FSGS recur mostly late secondary to reduced renal mass.
Risk factors for recurrence of FSGS :
1- Young age
2- High BMI
3- White race
4- Rapid progression to ESRD in native kidney
5- Pre transplant severe proteinuria
6- Low serum albumin at the time of diagnosis
7- 80% risk of recurrence in second transplant
Prevention and treatment of recurrent FSGS:
1- Pre transplant plasmapheresis and rituximab is of benefit to prevent recurrence and also used in treatment of recurrence
2- Protocol biopsy is important in early detection.
Summary
Introduction
This article is about the recurrence of FSGS post kidney transplant in adults. This occurs in one third of the cases and is associated with high risk of graft loss.
When there is no identifiable secondary cause, like infection or drugs, and the patient has a history of nephrotic syndrome, then it is known as FSGS idiopathic or primary.
Finer points to remember :
Conclusion :
FSGS can recur as idiopathic or secondary disease post transplant. It is difficult to distinguish between the two especially in obese patients. Patients need to be identified and treated promptly, since there is high risk of graft loss. Patient and graft outcome depend on response to treatment. Treatment can be plasmapheresis with or without rituximab. Using high dose IV cyclosporine is to be done at the disgression of the transplant team, since this measure carries the risk of further nephrotoxicity. Further analysis needs to be done in this area for definitive conclusions on adequate treatment.
Introduction:
FSGS causes renal failure in adults. When no secondary aetiology (genetic, viral, drug-associated, or adaptive) can be found, FSGS is primary or idiopathic. Differentiating between idiopathic and secondary causes is difficult without ultrastructural kidney biopsies or genetic testing.
Patients considering kidney transplantation must distinguish between idiopathic and secondary FSGS because idiopathic forms usually reoccur in the graft, leading to graft loss. Recurrence rates are 17–55%.
Study Design: a multicenter, retrospective study on patients from 15 kidney transplant centres. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. All patients with secondary FSGS (clear secondary aetiology, minor foot process effacement by EM, no nephrotic syndrome, short FU 6 months), were excluded.
Results:
-Only 176 of the 11,742 kidney transplant patients who were examined for FSGS and included in the study were found to have a diagnosis of idiopathic FSGS.
-32 per cent of patients had a recurrence of FSGS, with a 95 per cent confidence interval (CI) ranging from 25 per cent to 39 per cent; 57 patients had a recurrence of FSGS, and 39 per cent of those patients lost their graft after a median of 5 years
-The results of a multivariable Cox regression showed that an increased age at the beginning of native kidney disease was associated with an increased risk for recurrence.
–-nephrectomy of native kidneys has been associated with a higher risk for recurrence.
Additional variables were a white race, body mass index at the time of transplant (hazard ratio of 0.89 per kg/m2; 95 per cent confidence interval of 0.83 to 0.95), and native kidney nephrectomies.
-Recurrence patients had a lower BMI at transplant.
The therapies that were used most often were plasmapheresis and rituximab (81 per cent). Remission, either partial or full, was seen in 57% of patients, and this finding was related to improved graft survival.
Limitation:
The retrospective design might have caused selection bias.
Further, not all confounders could be adjusted. Clinicians at participating institutions selected FSGS patients based on history and histology. Although secondary causes and biopsy reports were acquired to decrease variance, centre-to-centre discrepancies may still exist. Less than 1/3 of patients had EM pathology. Missing genetic testing.
Conclusion:
-Plasmapheresis combined with or without rituximab was the primary form of therapy, and a positive response to this treatment was related to improved outcomes in almost half of the patients. One patient out of every three had recurrent idiopathic FSGS, which increased the chance of allograft failure by a factor of five.
Thanks, Weam
Introduction
FSGS is one of glomerular disease that can progress to ESRD, FSGS classified as primary or idiopathic and secondary FSGS due to many causes like autoimmune disease, drugs toxins, infections, reduced nephron mass (adaptive hyperfiltration), obesity. Sometimes difficult to differentiate between primary and secondary FSGS is especially the absent of genetic testing or missing electron microcopy studies. Upon kidney transplantation it’s very important to differentiate primary vs secondary or genetic or inherited type of FSGS, as primary FSGS associated with higher rate of early recurrence post-transplant and can be associated with graft failure with in firt 3 months while secondary FSGS less aggressive and associated with lower rate of relapse with good prognosis .
Aim of the study
Tango group study is a large observational multicenter, international study aim to determine the incidence of glomerular disease recurrence post transplantation also to Identify the predictors and treatment response and clinical outcomes of recurrence glomerular diseases including FSGS recurrence post kidney transplantation from 2005-2015.
Inclusion criteria: all adults kidney transplant recipients with age of ≥ 16 years old, with biopsy confirmed primary FSGS in native kidneys all data collected retrospectively from the central electronic records
Exclusion criteria all recipients with the diagnosis of secondary FSGS ( clear secondary cause , minimal foot process effacement by EM, no evidence of nephrotic syndrome , short FU < 6 months
Results
Large cohort study including > 11, 700 cases of kidney transplant recipients with recurrence of idiopathic FSGS was found in 32% (1/3 of cohort). with fivefold increased rate of graft lost over 5 years Follow up intervals (39%).
Combination of plasmapheresis and rituximab was the predominate type of treatment in > 81% of cases with partial and complete response achieved in 57% with better graft survival. Factors predict the increased risk rate of FSGS recurrence include older age at time of transplantation, white race, native kidneys nephrectomies, BMI at time of transplantation . Geographical rate of recurrence was higher rate of FSGS relapse in US population compared to Brazil and Europe.
Strength of the study:
Multicenter international cohort with Large sample size of Divers populations (south-American ,US , Europe) and logistically possible and good base for future studies
Long follow-up period for secondary outcome
Limitation
Retrospective study with selection bias
no centralization of selection criteria with variation between centers
EM pathology available for 36 cases (Less than 1/3 of cases)which add bias for the selection criteria
missing values for some predictors risk like 23% missing of values for predictors of ESRD outcome.
Genetic testing available for few cases .
conflicting finding regarding some predictors factors may be explained again by bias selection like older age and lower BMI association with higher recurrence rate should be carefully interpreted in this study .
no standardized treatment guideline used for the recurrence FSGS in this cohort including type and duration of treatments used .
.
please this is my final draft
Thanks, Saja
Introduction
FSGS is one of glomerular disease that can progress to ESRD, FSGS classified as primary or idiopathic and secondary FSGS due to many causes like autoimmune disease, drugs toxins, infections, reduced nephron mass (adaptive hyperfiltration), obesity. Sometimes difficult to differentiate between primary and secondary FSGS is especially the absent of genetic testing or missing electron microcopy studies. Upon kidney transplantation it’s very important to differentiate primary vs secondary or genetic or inherited type of FSGS, as primary FSGS associated with higher rate of early recurrence post-transplant and can be associated with graft failure with in firt 3 months while secondary FSGS less aggressive and associated with lower rate of relapse with good prognosis .
Aim of the study
Tango group study is a large observational multicenter, international study aim to determine the incidence of glomerular disease recurrence post transplantation also to Identify the predictors and treatment response and clinical outcomes of recurrence glomerular diseases including FSGS recurrence post kidney transplantation from 2005-2015.
Inclusion criteria: all adults kidney transplant recipients with age of ≥ 16 years old, with biopsy confirmed primary FSGS in native kidneys all data collected retrospectively from the central electronic records
Exclusion criteria all recipients with the diagnosis of secondary FSGS ( clear secondary cause , minimal foot process effacement by EM, no evidence of nephrotic syndrome , short FU < 6 months
Results
Large cohort study including > 11, 700 cases of kidney transplant recipients with recurrence of idiopathic FSGS was found in 32% (1/3 of cohort). with fivefold increased rate of graft lost over 5 years Follow up intervals (39%).
Combination of plasmapheresis and rituximab was the predominate type of treatment in > 81% of cases with partial and complete response achieved in 57% with better graft survival.Factors predict the increased risk rate of FSGS recurrence include older age at time of transplantation, white race, native kidneys nephrectomies, BMI at time of transplantation . Geographical rate of recurrence was higher rate of FSGS relapse in US population compared to Brazil and Europe.
Strength of the study:
Multicentral international cohort with Large sample size of Divers populations (south-American ,US , Europe)
Long follow-up period for secondary outcome
Limitation
Retrospective study with selection bias
EM pathology available for 36 cases (Less than 1/3 of cases)which add bias for the selection criteria
Big missing values for some predictors risk like 23% missing of values for predictors of ESRD outcome.
genetic testing missing.
Very good
Introduction
FSGS recurrence after kidney transplantation is one of the causes of high risk of the allograft loss
Generally, the course of the disease, risk factors and response to treatments are yet clearly identified
This study was focused to access the incidence, risk factors, and treatment response of the recurrent FSGS
Methodology
Results
Discussion
Limitation
Conclusions
Clear ,very good
Thnxs prof
Differentiating primary FSGS from secondary is difficult meanwhile it is important to be differentiated because primary FSGS is common to recur after transplantation with subsequent graft loss.
This study collected retrospective data of patients with biopsy-proven FSGS from 15 centers and report FSGS recurrence rates, risk factors for recurrence, and responses to treatment.
The results included 176 patients with biopsy-proven primary FSGS, with57% had recurrence of FSGS early post transplant
The patients in the recurrence group had multiple transplants ,and more nephrectomy of native kidney and lower BMI.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
13% of the cases who had partial remission experienced graft loss after 3.2 and 6.4 years after recurrence, whereas ten patients with complete remission did not experience graft loss.
FSGS recurrence cases had fivefold higher risk of graft loss.
FSGS recurrence was correlated with BMI at transplant , age and white race and native kidney nephrectomy .
Centers in Brazil and Europe had lower recurrence rate compared to USA.
Cases who had allograft loss due to etiologies other than recurrent FSGS were associated with a lower incidence of FSGS recurrence in the new allograft.
Plasmapheresis with or without rituximab was given to most of the cases and the only one inducing complete remission.
Increased immunosuppression intensity in cases with recurrent FSGS may lead to a higher risk of infectious complications as BK virus and cytomegalovirus reactivation.
Proteinuria detected in cases without remission or with partial remission was higher than in those with complete remission.
eGFR was progressively decreasing in cases without or with partial remission.
Discussion
FSGS recurred in 32% of patients, with subsequent graft loss in 39%.
older age, native kidney nephrectomies, white race, and lower BMI at transplant was accompanied with a higher risk for recurrence. Recurrent FSGS was treated with plasmapheresis with or without rituximab, leading to partial or complete remission in 57% of patients.
Determination of age at diagnosis need to be revaluated
There is no enough data on the effect of ethinicty on recurrence of FSGS.
APOL1-related FSGS is not accompanied with greater risk of recurrence post-transplantation
Nephrectomy of native kidneys incidence is low and is done in severe disease, that can bias outcomes.
Obesity-induced FSGS as a secondary cause can be misdiagnosed as primary FSGS.
Cases were treated with plasmapheresis with or without rituximab
Limitations of the study included being retrospective ,lack of unified selection of FSGS cases and adjusting the cofounders and lack of genetic testing.
Good
Please give a summary of this article
Introduction
Primary, or idiopathic, FSGS frequently recurs after kidney transplantation with an increased rate of the graft loss.
Recurrence rates in literature varied depending on the size of studies(17%-55% small studies; 9%-15% in registries).
Materials and Methods
Study Design
TANGO study was a multicenter, retrospective study in 15 renal transplant centers in Europe, Brazil, & the US.
All adults who were kidney transplanted from Jan 2005-Dec2015 were reviewed.
Objectives
The primary objective was to define the incidence of FSGS recurrence post-transplant in idiopathic FSGS.
Also the study aimed to assess:
– Risk factors for FSGS recurrence
– Clinical outcomes of recipients with & without recurrent FSGS
– Effect of treatments on recurrent FSGS outcomes.
Patients & Data
Patients with idiopathic FSGS (biopsy-proven) were included.
All patients with secondary causes of FSGS were excluded.
Statistical Analyses
T test used for continuous variables analysis.
Chi-squared or Fisher test for binary & categorical variables.
Confidence intervals were calculated by Wald testing.
Results
Cohorts
A total of 11,742 post-kidney transplant patients were screened for FSGS; 253 patients with idiopathic FSGS
were included.
Finally, 176 patients with biopsy-proven primary FSGS, who fulfilled all criteria, were included for analysis.
Recurrence of FSGS
Recurrence occurred in 57 patients (32%).
Most recurrences were early post-transplant.
Median time to recurrence: 1.5 months.
FSGS recurrence & graft survival
Graft loss seen in 15% without recurrence & in 39% with recurrence.
Graft loss was confined to those who failed to remit.
Recurrence was associated with a 5-fold increased risk of graft loss.
Predictors of higher FSGS recurrence were:
Lower BMI at the time of transplantation.
Prior native kidney nephrectomy.
White race
US centers(Brazil & Europe have lower recurrence rates).
Prior loss of a graft to FSGS.
Older age at disease onset.
No association between time to ESRD & recurrent FSGS.
Response to Treatment of Recurrent FSGS
IS treatments included steroids, cyclosporine, PP, rituximab, cyclophosphamide, & IA.
PP (with or without rituximab) was the most frequent treatment, & the only one inducing complete remission.
PP with or without rituximab was associated with complete remission in 21%, partial remission in 36%, & no response in 43%.
Thirty-two patients received both PP & rituximab, 25 received only PP, & 3 only rituximab.
Younger age at transplantation & female sex had a trend for a higher response to treatment.
FSGS recurrence & post-transplant complications
Incidence of BK or CMV viremia, AR rates, or cancer
Was similar between recurrence & non-recurrence patients.
No difference in DGF or diabetes between the two groups.
Graft Function
Proteinuria was higher in those with partial or no remission versus complete remission.
eGFR in complete remission patints was similar to those with no recurrent FSGS.
In partial or no remission, eGFR was lower & declined progressively.
Limitations of the study:
It is retrospective one, thus possibility of selection bias.
Selection of patients with FSGS was not centralized.
The lack of genetic testing in most patients; this causes a bias as genetic FSGS does not recur.
Thanks, Mohamed
Recurrence of FSGS after Kidney Transplantation in Adults.
Observational(retrospective), multicenter, international cohort study (TANGO)which aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in recipients with biopsy-proven native kidney idiopathic FSGS from 15 centers.
Total number of patients were 11,742 from different centers and 176 patients with biopsy-proven primary FSGS were included for analysis after inclusions and exclusions criteria were established.
Recurrence of FSGS occurred in 57 patients with median time of recurrence 1.5 month.
Risk factors of recurrence are (prior transplantation ,low BMI ,white race ,old age and prior nephrectomy of native kidneys).
Recurrence of FSGS is associated with reduced graft survival, especially in patients with no response to treatment.
Graft failure occurred in 18 patients (15%) without recurrence and in 22 patients with recurrence (39%).
Treatment of recurrent FSS:
Plasmapheresis with or without rituximab was the most frequent treatment (81%) and the only one inducing complete remission which was 21% and partial remission on 36%.
High risk of post-transplant complications were in patients with recurrent FSGS due to immunosuppressive medication.
Graft failure was common in patients with no remission mainly due to residual proteinuria.
Weakness points of the study were :
Bias of selection in retrospective study.
Selection of patients done by local center clinician not by centered one.
Lack of genetic testing to exclude genetic FSGS.
Summary:
FSGS is a leading cause of ESRD in adults.
It is of 3 types:
Differentiation between primary and secondary forms is essential in patients considered form transplantation as the idiopathic disease tends to recur post-transplant with a possibility of graft loss.
Because FSGS is rare, most of the studies are limited by a small sample size, and the larger registries are missing some data rendering them unreliable for drawing robust conclusions.
So, the TANGO study was established to combine the single-center studies with larger registry data.
Study design:
A multicenter, retrospective study including patients from 15 kidney transplant centers in Europe, Brazil, and the US.
Aim:
To determine the incidence of FSGS recurrence after transplantation in patients with idiopathic FSGS and risk factors for recurrence, compare clinical outcomes of patients with and without recurrent FSGS and evaluate the effect of different treatments on recurrent FSGS outcomes.
Inclusion criteria:
Exclusion criteria:
Patients with secondary causes of FSGS are determined by kidney biopsy and/or clinical features.
Patients:
The total number of patients was 11742; 11489 were excluded because they did not have FSGS, so 253 patients with FSGS were studied. Another group of patients were excluded due to either having a secondary cause of FSGS, loss of follow-up, unfit for age inclusion criteria or having no biopsy. Hence, the final number of included patients is 176, 57 had recurrent FSGS, and 119 had not.
Data were extracted from the medical records of all patients included in the study.
EM evaluation of kidney biopsy was available for 36 patients.
Results:
Fifty-seven patients had recurrent FSGS, and 39% lost their graft at around five years post-transplant.
Risk factors for recurrence:
The most frequent treatment, PLEX and rituximab, resulted in partial or complete remission in 57% of patients and were associated with better graft survival.
Limitations:
Conclusion:
Idiopathic FSGS recurs post-transplant in one-third of the cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
Thanks Dr Al-Taee
.-FSGS is one of the leading glomerular causes of ESRD in adults .It can be primary or secondary.
-Distinguishing between idiopathic and secondary FSGS is especially important in patients being considered for kidney transplantation because idiopathic
forms frequently recur in the graft with a substantial rate of subsequent graft loss.
-It is a multicenter, retrospective study in patients from 15 kidney transplant centers participating in the TANGO study in Europe, Brazil, and the United
States.
– Primary objective was to determine the incidence of FSGS recurrence after kidney transplantation in patients with idiopathic FSGS.
-It aimed also to identify risk factors for FSGS recurrence, to compare clinical
outcomes of patients with and without recurrent FSGS, and to evaluate the effect of different treatments on recurrent FSGS outcomes.
-study showed that FSGS recurred in 32% of patients, with subsequent graft loss in 39%.
-Risk for recurrence: older age at primary disease onset, native kidney nephrectomies, white race, and lower BMI at transplant to be associated with a higher
-Recurrent FSGS was most often treated with plasmapheresis with or without rituximab, and this regimen resulted in partial or complete remission in 57%
of patients.
. The fact that older age at onset was a predictor of recurrence may capture
the fact that some cases diagnosed at younger age were, in
fact, genetic and less likely to recur .
-Black (or mixed race) patients, have a higher prevalence of APOL1
high-risk alleles that are associated primarily with FSGS and APOL1-related FSGS is not associated with greater risk of recurrence post-transplantation .
-nephrectomy of native kidneys has been associated with a higher risk for recurrence.
-Response to treatment was associated with graft survival, as graft loss mainly
occurred in patients who failed to enter remission.
– Limitations of study :
1. its retrospectivedesign, which could have resulted in selection bias.
2.Lack of genetic testing in most patients, which might create bias as genetic FSGS usually does not recur after transplantation .
Thanks, Dr. Reem
FSGS recurrence post transplant is associated with high risk of graft loss.
The differentiation between idiopathic and secondary FSGS is difficult and challenging. However it is important because idiopathic forms frequently recur post transplant and result in graft loss.
The post transplant glomerular disease (TANGO) study is a large, multicenter, international study use a standardized approach to study recurrence of glomerular disease post transplant.
It is a retrospective study aimed to determine incidence of recurrent FSGS, risk factors for recurrence and the effect of treatment on graft outcome.
It included patients with biopsy proven native kidney diagnosis of idiopathic FSGS and excluded patients with secondary FSGS.
It showed that
Limitations:
Retrospective study which may lead to selection bias.
Couldn’t adjust all potential confounders.
Selection of patients with FSGS was not centralized
Genetic testing was not made in most patients.
Excellent Heba
Focal segmental glomerulosclerosis can recur after kidney transplant and is an important cause of graft loss. It can be primary or secondary due to viral infections, genetic, drug induced or adaptive. Differentiation between two is challenging if ultra structural picture of biopsy and genetic testing is not available. Differentiation between the two is important as idiopathic can recur in graft post transplantation. Data on recurrence is limited to small studies, To address this TANGO ( Post transplant Glomerular disease ) study was established .MethodologyMulticentre retrospective study from 15 transplant centres across Europe , Brazil, United states.. This study included 176 patients with idiopathic FSGS. Primary Objective
To determine the incidence of recurrence of FSGS post transplant in patients with idiopathic FSGS
To identify risk factors of FSGS recurrence
To compare outcome of patients with and without recurrence of FSGS
To evaluate different treatments
Results.
Risk factors for FSGS.
Old age at onset
Native Nephrectomy
Low BMI at transplant time
White Race
Recurrence Rate of FSGS was 32%
Graft loss in 39 % after recurrence of FSGS at 5 years
PLEX with and without Rituximab was used as treatment
Response rate with PLEX and Ritxuximab -Complete remission in 13 patients-21%
Partial remission in 36% and no response in 43%
Limitations
Retrospective design
Selection Bias
Low no of patients per centre
Lack of genetic testing
Excellent Dr Khan
This is how to summarise articles. Thank you for your structured writing. Do you agree with the risk factors mentioned in this article?
No Sir
Risk factors for recurrent FSGS
These include :
Onset during childhood
Rapid progression f primary FSGS to ESRD
Recurrent FSGC in previous Graft
Diffuse mesangial hypercellularity
Collapsing variant of FSGS in native kidney
White Race
Reference-
Shoji J, Mii A. Terasaki M, Shimizu A. AUpdate on recurrent FSGS in kidney transplantation. Nephron 2020;144(suppl 1):65–70
FSGS is an important cause of ESRD adult patients. It classified into primary & secondary ( genetic, viral, drug or adaptive). It is very difficult & important to distinguished between 2 types with out ultrastructural changes in biopsy & genetic test.
TANGO study is an international network of centers ( 3 different countries), it study the recurrence of glomerular disease after renal transplantation with a standardized approach to data & bio sample collection.
Retrospective study include 15 KTx centers aimed to:
All adult patients who receive renal transplant( Jan 2005-Dec2005) with diagnosis of idiopathic FSGS were included.
Result & discussion:
Thanks Ban
FSGS is classified according to the etiology into:
The current study included 176 patients with confirmed idiopathic FSGS and assessed the recurrence rate, graft survival after recurrence, and risk factors associated with recurrence with further evaluation of treatment of recurrent disease
Results
Risk factors for recurrence of primary FSGS in this study was
Tanks, Sherif
Please give a summary of this article :
1- old age at native kidney disease.
2- white race.
3- BMI.
4- native nephrectomy.
Thanks, Ibrahim
Do you agree with the risk factors mentioned in this article?
0
Reply
1- onset of FSGS during childhood.
2- rapid progression of primary FSGS to ESRD…. less than 3 years
3- history of recurrent FSGS in previous allograft.
4- diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney.
5- Steroid-responsive FSGS in the native kidneys
6- white race patients
7- Pre-transplant bilateral nephrectomy. It is postulated that the native kidneys absorb some permeability factors, although data on nephrectomy are conflicting