II. Comparison of MDRD equations and the old equations CKD-EPI against new equations CKD-EPI in patients with kidney transplantation when used 51Cr-EDTA to measure glomerular filtration
- What is the type of the article?
- What is the level of evidence this article provides?
- Briefly summarise this article in your own words (please do not copy and paste).
- Do your own search and briefly discuss the validation of the various eGFR formulae and their applicability in renal transplantation!
- Discuss the best approach in monitoring graft function.
What is the type of the article?
This a retrospective study .
What is the level of evidence this article provides?
The level of evidence is level 3
Briefly summaries this article in your own words (please do not copy and paste).
The estimation of GFR is important to assess kidney function in kidney transplant . Different formulas are developed to estimate GFR in kidney transplant . Serum creatinine and cystatine C are used in these formulas.
Serum creatinine (Cr) is the main marker of kidney function(GFR) being used in daily clinical practice. But, the relationship between serum Cr and GFR is not as close as one would.
In kidney transplants the serum creatinine levels have a different relationship with GFR than in non-transplanted patients, which causes a overestimation of the actual kidney function calculated with these equations.
Steroids modify the serum creatinine/muscle mass ratio and may cause a discrepancy between serum Cr levels and kidney function, however other factors may be involved. Some studies indicate that in patients not taking steroids there is less overestimation of GFR however this effect is not that evident with time after transplantation. The use of trimetroprim may affect the calculation of GFR although it would have less impact on long-term stable transplantation. Thyroid hormones may decrease serum creatinine levels and raise cystatin C levels; most transplant patients should not have thyroid pathology, so the overall impact must be low.
The objective of this study is to analyses and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year.
In the kidney transplant population the GFR estimated by the CKD-EPI equations that use serum creatinine and cystatin C as markers of kidney function, show a greater bias than the MDRD-IDMS equation and the GFR is measure by plasma clearance of 51Cr-EDTA.
Do your own search and briefly discuss the validation of the various eGFR formulae and their applicability in renal transplantation!
Creatinine based formulas ;
Cr-based eGFR equations have never been demonstrated to improve the clinical recognition of changes in transplant function, compared to the use of Cr alone, and many transplant injuries occur without change in SCr level or eGFR.
MDRD;
MDRD formulas underestimate GFR in patients with relatively well-preserved kidney function.
The CKD-EPI equation;
shows improved estimation ability compared with MDRD equation, but still with suboptimal precision that limit the value of the CKD-EPI for monitoring changes in kidney function over time.
Nankivell;
Is the only one that was derived from kidney transplant recipients .
CyC-based formulas;
CyC-based eGFR equations are a stronger predictor of the risk of death and cardiovascular events, when compared with Cr, as well as the correlation of serum CyC with all-cause and cardiovascular mortality in chronic kidney disease (CKD).
CyC-based GFR;
CyC improves GFR estimation and mortality prediction, in comparison to various eGFR equations, in transplanted patients.
Cr- and CyC-based formula (CKD-EPI CyC equation)
The use of CyC alone or in combination with Cr reinforces the eGFR power as a predictor of end-stage kidney disease and death, in general and CKD population, but we need to confirm this outcome prediction in transplant recipients.
Discuss the best approach in monitoring graft function
Combining albuminuria and Cr- or CyC-based eGFR, performed better than those markers alone, to predict death censored graft loss, in kidney transplant recipients.
Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), and it potential in prediction of kidney function, not influenced by age, gender, race, body fat and muscle mass. Particularly, in kidney transplant recipients, it was demonstrated that urinary excretion of KIM-1, a proximal tubular protein, independently predicts graft failure .
Reference ;
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• The study is a retrospective study.
• Level of evidence III
• summary :
The analysis included 270 kidney transplant recipients and each patient had the measurement GFR using 51Cr-EDTA. The study analyzed the performance of the different equations to detect a GFR < 60mL/min/1.73m2. 99.6% of patients were on prednisone (3.5−5mg/day in 95% of the cases) when the GFR was measured. Most patients had received cadaveric graft (89.6%).
After one year of follow up, only about 50% of the change in mGFR could be predicted by serum creatinine, cystatin C, sex and age, indicating that there are other very influential beyond the control variables.
All equations overestimated GFR, with a mean bias of +11.1ml/min/1.73m2 for MDRD, +16.4ml/min/1.73m2 for 2009-CKD-EPI, +15 ml/min/1.73m2 for CKD-EPI with cystatin C and +14.1ml/min/1.73m2 for 2012-CKD-EPI with creatinine and cystatin C.
eGFR by MDRD and the 2009 CKD-EPI equation correlated better with 51Cr-EDTA than CKD-EPI with creatinine and/or cystatin C. MDRD-IDMS equation showed the highest sensitivity, while the highest specificity was obtained with the CKD-EPI-Cr +CystC equation, which is expected since the latter results in estimates greater than MDRD-IDMS and when creatinine and cystatin C levels are sufficiently elevated, the estimate for GFR is clearly below 60mL/min/1.73m2. Positive predictive values are similar for all equations while negative predictive values are slightly better for CKD-EPI equations.
• All of the above methods have their limitations and biases regarding the estimation of GFR in the general population as well as in transplant donors, as the use of serum creatinine and cystatin c is limited by many factors such as age, BMI, gender, diet, medications, even inflammation, steroid use, thyroid disease can interfere with the clearance of cystatin c.
• Practically, we still use the MDRD equation as part of transplant works as well as for following up. For the donor, we use GFR measured by EDTA isotope scan.
It is a retrospective study level of evidence 111.
Estimated GFR in kidney transplant patients can be done by many equations, the commonest formulae:
Cockcroft –Gault:
MDRD.
CKD-EPI .
CKD-EPI combined creatinine and cystatin c.
CKD-EPI is more accurate than MDRD EQUATION AND BOTH BETTER THAN Cockcroft and Gault.
In the study, the kidney transplant population, the GFR estimated by the CKD-EPI
equations that use serum creatinine and cystatin C as markers of kidney function, show
a greater bias than the MDRD-IDMS equation and the GFR is measured by plasma
clearance of 51Cr-EDTA.
These equations produce a significant overestimation of the GFR if the eGFR is greater
than 60mL/min/1.73m2, however, the error obtained is reduced below the observed
with the MDRD-IDMS equation if the GFR is less than 30mL/min/1.73m2.
The degree of precision with all the equations was low in all stages of the CKD.
It is important to take into consideration the reference technique used to measure GFR
in kidney transplants when analyzing the performance of the different MDRD-IDMS or
CKD-EPI equations.
.A retrospective study.
.level 3
.Regarding kidney transplant population, GFR determined by CKD-EPI equations (using serum creatinine and cystatin C as markers of kidney function), show greater bias than the MDRD-IDMS equation and GFR is measure by plasma clearance of 51Cr-EDTA. These equations have significant overestimation of the GFR if eGFR is more than 60 mL/min/1.73 m2 ,.However, error is reduced below the observed with the MDRD-IDMS equation if the GFR is less than 30 mL/min/1.73 m2 . The level of precision with all the equations was low in all stages of the CKD. It is important to take into consideration the reference technique implemented to measure GFR in kidney transplants when analyzing the performance of the different MDRD-IDMS
.Follow up monitoring of kidney transplants is a widely accepted practice of post-transplantation care. Underlying rationale is to evaluate transplant is stability by checking kidney function. Despite issues related to sensitivity and specificity, estimating serial serum creatinine levels is the most common approach to evaluation of kidney function.
This is retrospective study evidence level three it’s a summary is estimation of glomerular filtration rate GFR of the kidney transplant patients with use of exogenous markers as inulin and isotopes is more accurate but more expensive and less available then serum creatinine and creatinine based formulas
CKD EPI equation that use serum creatinine and cyctatine C as markers of kidney function show a greater Bias than the MDRD IDMS equation , significant over estimation of GFR iF GFR greater than 60 ml per minute
1-retrospective study
2-level 3
3- study comparison between MDRD-CKD EPI old and newest one in calculating gfr
by following 270 transplanted patient-different weights-BMI-diapetics or not-received cadaveric or living kidney donor-on different immunosuppressive drugs
study reveal that all equation over estimate GFR when using 51Cr-EDTA to measure GFR but MDRD is the best one as the other equation became further more over estimated as (CKD EPI )weather old or newest one.
4-MDRD use(s.cr-age-race-sex)
-cockcroft use (s.cr-age-sex-body weight)
-CKD-EPI 2009 use (s.cr-age-sex)
-CKD-EPI 2012 cystatin C(age-sex-serum cystatin C)
also their are inulin, iothalamate, 99mTc-DTPA or 51Cr-EDTA but expensive and not always available.
5-the best method in monitoring graft function by follow s.creatinine -proteinuria-may use protocol biopsy to detect early pathologic changes -may use new markers as N-GAL to evaluate graft function,stil in need to calculate GFR to adjust drugs.
retrospective study.
Level of evidence: three
.
The estimation of (GFR) is essential to evaluate kidney function in patients with kidney transplant.
1- Direct measure eGFR using inulin, iothalamate, 99mTc-DTPA and cr-EDTA ( unavailable and expensive).
2- indirect ( equations):
a- MDRD
b- CKD-EPI use creatinine
c- CKD-EPI use cystatin C
d- CKD-EPI use creatinine and cystatin C
The study in this article showed a significant overestimation of GFR in kidney transplants patients using indirect measure (equations) as compared with the GFR measured as the plasma clearance with 51Cr-EDTA. As immunosuppression drugs increased the level of cystatin C and serum creatinine
1- GFR more than 60ml/min/1.73 m2, MDRD equation was shown to be more reliable and more sensitive , while CKD-EPI-Cr + CystC equation is the most specific.
2-MDRD equation was more reliable for classification of CKD into stage 1 and 2 where creatinine and cystatin C based CKD-EPI was more reliable in more advanced kidney disease.
3- Estimation equations were not accurate in patients with BMI< 20.
4-Serial measurement of serum creatinine with the proper use of eGFR equations as MDRD and CKD-EPI may be the best method of monitoring renal functions after transplantation
5- No standard available and accessible method to estimate truly GFR until now
Comparison of MDRD and old EPI against new EPI in patients with kidney transplantation this is a Canadian retrospective study of 270 kidney transplant patients one year after kidney transplantation. All patients were above 18 years old and have a stable kidney function.89.6 had cadaveric transplant and 99.6 were on prednisolone.
The measured GFR (mGFR) was measured through plasma clearance of cr 51 EDTA. Each patient was tested for serum creatinine and serum cystatin c simultaneously. Then MDRD, EPI-Cr2009, EPI-Cr+CystC2012 and EPI-CystC 2012 were applied. Accuracy was calculated through absolute bias, RMSE, P10 and P30 , sensitivity, specificity and predictive values .
mGFR correlate significantly with serum Cr and serum Cystatin C .
absolute bias of EPI-Cr was more than that of MDRD for the entire group and even in subgroups and they are not related to mGFR values. At GFR equal or more than 60, the EPI is more by 9 ml from MDRD. Regarding EPI-Cr and EPI-Cr+ Cyst C values were more than that of m GFR and MDRD.
mGFR had a statically significant association with MDRD,EPI-Cr , EPI-Cyst C and EPI Cr+ Cyst C.
The statistical association between each of the following were significant : bias of MDRD and MDRD, bias of EPI-Cr and EPI-Cr, EPI-Cyst C and EPI-Cyst C,EPI-Cr+ Cyst C and EPI- Cr+ Cyst C.
on the other hand , none of the mentioned absolute bias above had a significant statistical association with mGFR.
Regarding RMSE , EPI-CysC has higher result than the other three equations except in stage 4 CKD where EPI-CysC had similar results to EPI-Cr . EPI-Cr+ Cyst C is more than MDRD in all CKD stages except for stage 4
EPI-Cr+Cyst C had more bias than MDRD and m GFR.it overestimates if GFR is more than 60 but not if GFR is less than 30.
The accuracy of detection of GFR below 60 (91.9% in the study)by the four equations were as follows : 67% MDRD, 61.1% EPI-Cyst C, 57.8% EPI-Cr+Cyst C , 56.3%EPI-Cr.
The highest sensitivity for detection of GFR which is less than 60 was achieved with MDRD72.2%, which also has the highest negative predictive value of 22.5%. the highest specificity was achieved by EPI-Cr+Cyst C (100%) .The positive predictive value of all four equation were on the same range. EPI-Cyst C has the lowest parameters while MDRD has the best.
So, from the above results we can say that the precision of all four equations were low in all stages .
1- this article was a retrospective study.
2- its level of evidence is III.
3- this article discussed the variable methods for assessment of GFR. it included the variable formulae as following :
a- Cockroaft- Gault formula that included age, sex and body weight as significant variables for an approximate assessment of GFR. however, it will overestimate GFR in obese and edematous pts.
b- MDRD. it is very recommended in early renal impairment ( stage I & II ). it underestimates GRF in pts who are young, females and those with low S. creatinine. it is even not applicable in pregnant females, asians and those at extremes of age.
c- CKD-EPI with creatatinine and/or Cystatin-C
it is valuable in young pts, females and those with low S. creat.
however, it significantly overestimates GFR in early kidney disease.
4- the different formulae used in monitoring of graft function in renal transplantation have some limitations due to older age, low muscle mass, use of steroids & other drugs…. etc
5- the best approach in monitoring graft function is simply with serial follow up of the S. creatinine with comparing its value to the baseline one. also urine analysis for routine check-up of any sediments, casts, proteinuria …..etc. periodic microalbuminuria is also needed for checking any worsening.
Its retrospective study level of evidence 111.
Though measurement of GFR by an exogenous substance like inulin ,iothalamate is
accurate ,its costly and time consuming.
Estimated GFR done by many equation common:
Cockcroft –Gault:
MDRD.
CKD-EPI .
CKD-EPI combined creatinine and cystacin.
In an attempt to find simple way of estimation of GFR in transplant patient.
CKD-EPI is more accurate than MDRD EQUATION AND BOTH BETTER THAN Cockcroft and Gualt.
The study compare measurements with 51Cr-EDTA.
The measurement of GFR using the plasma clearance of 51Cr-EDTA (mGFR) was
performed by the Nuclear Medicine Service and compare to MDRD and CKD-EPI.
The estimated eGFR using the MDRD-IDMS and CKD-EPI-Cr equations was significantly
higher (p < 0.001) than the mGFR.
The values of eGFR with CKD-EPI-CystC and CKD-EPICr +CystC were greater
(p < 0.001) than the mGFR .
It shows The percent of patients misclassified were low for MDRD-IDMS in stages2 and
3 and higher in stage 4; misclassification was lower for the stage 4 with CKD-EPI-Cr
+CystC and CKD-EPI-CystC.
a significant overestimation of GFR in kidney transplants patients using the MDRD-IDMS
and the CKD-EPI equations of 2009 and 2012 as compared with the GFR measured as
the plasma clearance with 51Cr-EDTA.
In summary, in the kidney transplant population the GFR estimated by the CKD-EPI
equations that use serum creatinine and cystatin C as markers of kidney function, show
a greater bias than the MDRD-IDMS equation and the GFR is measure by plasma
clearance of 51Cr-EDTA.
These equations produce a significant overestimation of the GFR if the eGFR is greater
than 60mL/min/1.73m2, however the the error obtained is reduced below the observed
with the MDRD-IDMS equation if the GFR is less than 30mL/min/1.73m2.
The degree of precision with all the equations was low in all stages of the CKD.
It is important to take into consideration the reference technique used to measure GFR
in kidney transplants when analyzing the performance of the different MDRD-IDMS or
CKD-EPI equations.
It is retrospective study
– level of evidence 3
Summery ..
270 kidney transplant recipients one year post transplantation and more than 18 years old were enrolled in this study to compare the valdity of MDRD, CKD-EPI creatinine, CKD-EPI creatinine + cystatin c equations to 51 cr-EDTA.
All of the patients were on low dose steroid and the majority were male, most of the participants received
deceased donor kidney. mGFR was 43
Creatinine and cystatin c were measured for all patients at the same time with estimation of ⁵¹Cr-EDTA (mGFR).
Overall, eGFR by all equations is higher than mGFR.
the most sensitive equation was MDRD especially in patients with eGFR less than 60 mL/min/1.73 m² , while CKD-EPI-Cr + CystC equation is the most specific.
Also, MDRD showed more accurate and correct classification of patients in stages 2 and 3.
Cystatin c is superior to creatinine in GFR evaluation ,because it does not affected by multiple variables which influence the creatinine level. However it showed lower correlation with mGFR than that of creatinine.
To sum up :
MDRD equation is better in estimation of GFR than new CKD-EPI in stage 1&2 CKD ( if GFR more than 60), but in patients with GFR less than 60 ml/min/1.73m2 MDRD is more sensitive and new CKD-EPI is more specific.
1.This is a retrospective study.
2.level 3
3. kidney transplant population the GFR estimated by the CKD-EPI equations that use serum crea- tinine and cystatin C as markers of kidney function, show a greater bias than the MDRD-IDMS equation and the GFR is measure by plasma clearance of 51Cr-EDTA. These equa- tions produce a significant overestimation of the GFR if the eGFR is greater than 60 mL/min/1.73 m2 , however the the error obtained is reduced below the observed with the MDRD-IDMS equation if the GFR is less than 30 mL/min/1.73 m2 . The degree of precision with all the equations was low in all stages of the CKD. It is important to take into consideration the refer- ence technique used to measure GFR in kidney transplants when analyzing the performance of the different MDRD-IDMS
5.Ongoing monitoring of kidney transplants is a widely accepted and practiced part of posttransplantation management. One reason to monitor is to evaluate whether the transplant is stable. The transplant community evaluates stability by checking kidney function. Despite problems with sensitivity and specificity, obtaining serial serum creatinine levels is the most common approach to assessing kidney function.
This is a retrospective study, level 3 evidence
In summary
Creatinine the most daily used marker of kidney function is not equal to the true GFR especially in renal transplant patients.
In this study kidney transplant patients after one year of follow up, only 50% charges in mGFR could be predicted by serum creatinine, cystatin C, sex and age.
different equations are available to estimate GFR among the the MDRD and CKD-EPI-Cr + Cystatin C are the best used transplantation patients.
in kidney transplants the serum creatinine levels have a different relationship with GFR than in non-transplanted patients, which causes a overestimation of the actual kidney function calculated with these equations.
Steroids affects serum creatinine/muscle mass ratio and may cause a discrepancy between serum Cr levels and kidney function although some studies showd no effect in small doses.
cystatin C is better marker than creatinine for assessment of GFR as it is less affected by age, gender, race, body weight or muscle mass.
trimetroprim may affect the calculation of GFR although it would have less impact on long-term stable transplantation.
accurate measurements of GFR can be done using an such as clearance of the nonradioactive substances, like the contrast agent iohexol or inulin or radiolabeled agents, like 51Cr-ethylenediaminetetraacetic acid (51CrEDTA), 99mTc-diethylene-triamine-pentaacetate (99mTcDTPA) or 125I-iothalamate, but these techniques are invasive, time consuming and costly.
All equations overestimate eGFR compared to mGFR.
In patients with GFR more than 60ml/min/1.73 m2, MDRD equation was shown to be more reliable and more sensitive , while CKD-EPI-Cr + CystC equation is the most specific.
MDRD equation was more reliable for classification of CKD into stage 1 and 2 where creatinine and cystatin C based CKD-EPI was more relianle in more advanced kidney dieases.
Estimation equations were not accurate in patients with BMI< 20.
Retrospective study, level 3
It aimed at the comparison between estimated GFR and measured GFR using MDRD & CKD-EPI equations for e-GFR and 51 Cr-EDTA plasma clearance for m-GFR
In patients with kidney transplantation more than 1-year post-transplant.
Measured GFR (m-GFR) using exogenous markers like inulin, exactly measure the GFR.
Estimated GFR (e-GFR) using endogenous markers like s.creatinine and Cystatin-C. it is less accurate than m-GFR.
All estimated GFR formulas use endogenous markers (serum creatinine, newly Cyatatin-C incorporated as well).
Cr is not a perfect marker of kidney function because it is affected by many factors like age, sex, muscle mass, ethnicity, and drugs.
It does not detect the early change in GFR, and the initial rise in s.Cr reflects a marked change in GFR, and a marked change in s.cr with advanced kidney disease reflects only a small absolute reduction in GFR. The relation is not linear between s.cr and GFR
To decrease this variation, many equations develop with the incorporation of demographic and clinical variables as observed surrogates for unmeasured factors other than GFR that are affected by s.cr.
1- MDRD Equation:
· Used to not only estimate GFR but to follow changes in GFR.
· Become less accurate when GFR > 60 ml/min/1.73m2
· Not valid in a pregnant lady.
· Less accurate in age < 18 yrs and > 70 yrs
· Valid in a black race but maybe not in Indian and Philipino
2- CKD-EPI
It is more accurate than MDRD when GFR > 60 ml/min/1.73m2
3- CKD-EPI- Cr+cyst-C formula
it is superior to the previous one.
Cystatin-c as an endogenous marker is better than cr, as it is less affected with demographic variables although it is affected by steroid that used by transplant patients, and thyroid hormone.
Incorporation of these endogenous markers to the estimated GFR formula improves their accuracy but, remains less than that of m-GFR.
In Kidney transplant the used of exogenous markers to measure GFR shows that about 40- 72% of them have a GFR < 60 ml/min/1.73m2.
the best approach to follow transplant patients is to follow multimarker strategy, with the use of blood, and urine marker
Dear All
Thank you for your replies. Feel free to contribute to the discussion for those who did not. Also, let us not forget week 2.
Do your own search and briefly discuss the validation of the various eGFR formulae and their applicability in renal transplantation
An interesting article by Jamal Saleh from king Saud University which measured the accuracy and precision of the CKD EPI and MDRD predictive equations compared with glomerular filtration rate and measured by insulin clearance in Saudi population. This study compared 31 participants (23 CKD and 8 transplanted patients). The study showed that CKD-EPI has shown to be more accurate than other predictive equations. The study also reported that CKD-EPI cystatin C and creatinine equation had maximum bias compared with CKD-EPI and MDRD.in transplanted patients, CKD EPI showed superiority by accuracy when compared with MDRD. It is closer to measured GFR by inulin. This finding has been supported by study by White et al.
Another study by Levey et al showed that CKD -EPI creatinine was more accurate and less bias compared to urinary clearance by ionathalamate.
Cater et al estimated GFR in UK adult populations reported that a higher eGFR by CKD EPI, mostly seen among 18-59 years old as compared to MDRD.
Lujan et al found that MDRD equation predicts lower GFR than CKD EPI creatinine in a comparison of 85 living kidney donors using non radiolabeled Iothalamate clearance.
Dear All
Thank you for your replies. Feel free to contribute to the discussion for those who did not. Also, let us not forget week 2.
CKD -EPI equations has been developed to reduce the systemic under estimation that’s occurred in eGFR in young populations, female sex and lower serum creatinine levels that happens with MDRD.
CKD EPI 2009 improved the estimates with regards higher GFR values compared to MDRD equation.
Studies have showed the validity of the MDRD and CKD EPI 2009 in transplanted kidneys but the results has been heterogenous.
This study was a retrospective study recruited stable post kidney transplant patients. 99.6% of these patients were on low dose prednisolone and most patients were cadaveric kidney recipient (86.6%).It was level 3 evidence being retrospective study.
mGFR correlated with serum creatinine significantly. mGFR were higher in men and degree of correlation was greater than females. The correlation between mGFR and cystatin C lower than seru creatinine, and no difference between male and females.
Generation of linear regression models for mGFR as dependant variable using sex, age, creatinine and cystatin C. In the study only half of the GFR variability measured with the plasma clearance of 51 CrEDTA explained by regression models using those variables in transplanted kidneys.
MDRD IDMS and CKD -EPI-CR estimated higher eGFR than mGFR. Bias of eGFR CKD EPI Cr was 9mls higher among GFR >60. Average bias for MDRD-IDMS -11.1mls/min/1.73m2 followed by CKD-EPI-Cr+CystC-14mls.
eGFR CKD-EPI-CystC and CKD-EPI-Cr-CystC were greater than mGFR. The bias of them were lower than CKD-EPI-Cr.
MDRD-IDMS shown most sensitive with specificity lower than CKD-EPI-Cr+CystC, and slightly higher negative predictive value but CKD -EPI and better negative prediction. MDRD-IDMS had lower RMSE.
one of the important steps in transplant recipients followup is GFR. The mGFR (e.g. inulin, iothalamate) had high cost & not available widely, so many equations have been found using different markers as serum creatinine & cystitis C.
This study compare 51 Cr-EDTA with CKD-EPIcrea, CKD-EPI cys, & MDRD to find the easier & more valid equation to followup the transplanted patients. the study found that only 50% of patient who followed for 1 year have correlation of mGFR with serum creatinine, cystitis, sex & age, indicate that there are another variables affecting GFR.
Serum creatine level is inconsistent with GFR in transplant recipient & this lead to overestimation of renal function when tested by eGFR. While the result from using cystitis C as a marker for GFR is better than creatinine because cystatin C not affected by age, race, gender & weight, but it can be affected by high dose of steroids without real change in GFR.
The study results show that when GFR is > 60ml/mim/m2 there was an overestimation of GFR ( ~ 10ml/min/m2) when using CKD-EPI & had more bias than MDRD equation. But when the GFR < 60ml/min/m2 the bias was minimal for both equations. Also there was over estimation of GFR when calculated by CKD-EPIcre, cys,MDRD & compared with Cr-EDTA. several series that studied the GFR equations using cystatin C have difference in bias due to non standardization of techniques in measuring cystatin C. Another bias found in studies that use different endogenous markers (mGFR) so the researcher can’t not comparing studies that used different markers.
Although Nankivell equation originally applicator for transplant patients, but re-expressed MDRD equation found to be better in transplant setting.
CKD-EPI formula found to be the least formula had bias when compared with others, & more accurate.
References:
Salvador C., HartmannA., Asberg A., et al. Estimation of GFR in Kidney TransplantRecipients: Comparing Novel Commonly Used Equations in this Direct. 2017; 3(2).
BoFeldt-Rasmussen. Glomerular Filtration Rate Estimation in Renal and Non Renal Solid Organ transplantation. Nephron .2017;136: 298-301.
Townamchai N., Praditpornsilpa K. & Chawatanarat T., et al. The Validation of eGFR equation for renal transplant recipients. Clinical Nephrology. 2012; 79(3).
it is a retrospective study with level 3 evidence
summary-
use of exogenous markers such as inulin,iothalmate,99Tc-DTPA,51Cr EDTA to directly measure GFR in kidney tx shows that about 40-72% have a GFR<60ml/min/1.73m2.these techniques are expensive and not easily available.MDRD equation causes underestimation in younger population,female sex and lower serum creatinine levels.studies that analysed the validity of MDRD and CKD-EPI equation of 2009 found that in some studies there was a lower bias using CKD-EPI with respect to direct GFR measurement,while other studies found a greater overestimation of GFR with with the CKD-EPI equation and less bias with the MDRD equation.CKD-EPI equation of 2012 has less bias than that with MDRD.Relationship between serum creatinine and GFR is not close as one would expect with about only 50%of the change in GFR could be predicted by serum creatinine.serum creatinine thus causes overestimation of the actual kidney function calculated with the Egfr equations.one reason is steroids for overestimation in tx patients.cystatin c is less influenced by age,gender,race,body weight or muscle mass.in kidney transplant patients CKD-EPI equation using creatinine and cystatin c as markers of kidney function show a greater bias than the MDRD equation and the GFR measured by plasma clearance of 51Cr EDTA.above a GFR OF 60ml/min/1.73m2 CKD-EPI causes significant over estimation over MDRD whereas below GFR of 30ml/min/1.73m2 the error obtained is reduced below the observed with the MDRD equation.
A total of 97 adult Thai renal transplant recipients were studied.the 99mTc-DTPA plasma clearance was used as a reference GFR. the serum creatinine was determined by IDMS reference enzymatic methods and eGFR was estimated using MDRD equation,CKD-EPI equation and Nankivell equation.the study found that the caucasian derived eGFR equations could be applied to Thai transplant recipients with some bias.the CKD-EPI had the least bias compared with other eGFR equations.
The validation of estimated glomerular filtration rate (eGFR) equation for renal transplant recipients
Natavudh Townamchai 1, Kearkiat Praditpornsilpa, Tawatchai Chawatanarat, Yingyos Avihingsanon, Khajohn Tiranathanagul, Pisut Katavetin, Paweena Susantitaphong, Talerngsak Kanjanabuch, Kriang Tungsanga, Somchai Eiam-Ong
for graft monitoring serum creatinine,proteinuria estimation,BP,BKV nephropathy screening,lipids,CNI or mTor trough levels and CBC needs to be serially monitored as shown in the able.Surveillance biopsies particularly in sensitised patients and indication biopsies are also useful to monitor graft function.
Monitoring and Managing Graft Health in the Kidney Transplant Recipient Michelle A. Josephson
– The glomerular filtration rate (GFR) must be calculated to assess renal function in patients who have had a kidney transplant.
– Exogenous markers such as inulin, iothalamate, 99mTc-DTPA, or 51Cr-EDTA have been used to directly quantify GFR in kidney transplant recipients and demonstrate that 40-72 percent had a GFR of less than 60mL/min/1.73m2. These procedures are costly and not generally available for renal function monitoring.
– This is why multiple formulas have been created to measure kidney function in patients with chronic kidney disease (CKD) and kidney transplant patients with appropriate accuracy.
– Blood creatinine and cystatin C were chosen as the indicators for these equations because serum concentrations of these substances can be affected by variables other than GFR in kidney transplant patients.
– When the MDRD study equation was applied to a younger population, female sex, and lower blood creatinine levels, the CKD-EPI equations involving creatinine values were produced to reduce the systematic underestimating of the GFR.
– In 2012, the same group of researchers attempted to improve the equations’ predictions by including cystatin C as a second GFR marker, with only a minor increase in predictive value).
– However, the authors stated that the equations using cystatin C and creatinine should only be used to confirm the presence of renal failure, not to be applied frequently.
– The essential marker of renal function (GFR) utilized in everyday practice is serum creatinine (Cr).
– All of the equations played poorly in patients with a BMI of less than 20 kg/m2.
– For kidney transplant patients, after one year of follow-up, only about 50% of the changes in mGFR in serum creatinine, cystatin C, sex and age were predictable, indicating that there are more significant variables than ours. range. Control
– Steroids may alter the serum creatinine/muscle ratio and cause discrepancies between serum Cr levels and renal function, but other factors may be involved. Several studies have shown that patients not taking steroids overestimated GFR less, but this effect is not so evident over time after transplantation
– low-dose steroids used in long-term patients should not affect serum creatinine/muscle ratio
– Cystatin C levels can be discontinuously increased by high-dose steroids without actually altering GFR.
– Thyroid hormone can lower serum creatinine while raising cystatin C levels. Because the majority of transplant recipients should not have thyroid problems, the overall effect should be minimal.
– Trimethoprim use can influence GFR calculations. However, it has a minor impact on long-term transplant stability.
1- It is retrospective study.
2- level of evidence lll.
3-The estimation of glomerular filtration rate (GFR) is essential to evaluate kidney function in patients with kidney transplant. The use of exogenous markers as inulin, iothalamate, 99mTc-DTPA or 51Cr-EDTA to directly measure GFR in kidney transplant show that about 40-72% have a GFR 60mL/min/1.73m2. These techniques are expensive and not always available for monitorization of kidney function .Different formulas have been developed to estimate with sufficient precision the kidney function in patients with chronic kidney disease (CKD) and in kidney transplant patient. The markers chosen to develop these equations have been serum creatinine and cystatin C .The CKD-EPI equations using creatinine values were developed to reduce the systematic underestimation that occurred in the GFR with the MDRD study equation when applied to younger population, female sex and lower serum creatinine levels.The studies that have analyzed the validity of the MDRD and CKD-EPI equations of 2009 in kidney transplant patients have obtained not uniform results, some found a lower bias using CKD-EPI with respect to direct GFR measurement, while others continue to observe a greater overestimation of the GFR with this CKD-EPI equation and less biases with the use of MDRD formula. It has been observed that the CKD-EPI equation from 2012, has less bias that the MDRD. The relationship between mGFR and serum concentration of creatinine and cystatin C . The mGFR correlated significantly with the serum creatinine values (r = -0.64, p < 0.001) . It is observed that. the values of mGFR were higher in men, and degree of correlation was also greater in male than females (males r = -0.75, p < 0.001; women r = 0.58, p < 0.001) .Comparison of mGFR with eGFR MDRD-IDMS and CKD-EPI-Cr . The estimated eGFR using the MDRD-IDMS and CKD-EPI-Cr .Equations was significantly higher (p < 0.001) than the mGFR. The values of eGFR with CKD-EPI-CystC and CKD-EPI-CR +CystC were greater (p < 0.001) than the mGFR. being also greater than eGFR MDRD-IDMS globally. Comparison of accuracy values of P10 and P30, sensitivity, specificity and predictive values mGFR60ml/m/1.73m2.
4- CKD-EPI Mostly widely used to estimate GFR and accurate equation when GFR more than 60 ml/min/1.73m2.
A newer CKD-EPI creatinine cystatin C is the most accurate serum cystatin creatinine cystatin C is known.
MDRD equation is not accurate to estimate high GFR , it performs like CKD-EPI equation when
GFR less than 60ml/mum/1.73m2.
However we must be alert for increasing serum creatinine level, proteinuria or other urinary abnormalities despite high GFR.
Creatinine clearance obtained by using 24 urine collection consider better for measurement of GFR than serum creatinine.
Radionuclide imaging provides the most accurate measurement of GFR and the gold standard in research. It used for accurate determination of GFR. during evaluation of kidney donors , evaluation of recipients for other organs or assessment of differential of the GFR of each kidney before nephrectomy .
5- * creatinine clearance by 24 h urine collection.
* baseline kidney function using serum creatinine.
* check vitals , uop , routine lab include blood count , chemistry profile for renal panel, IS levels and renal transplant us with doppler .
It is an original article, retrospective study by moderate level of evidence (level 3)
This study has compared the performance of MDRD and different version of CKD-EPI (2009, Cr based and 2012, cystatin C/Cr based) equations with measured GFR by 51Cr-EDTA plasma clearance.
All equations overestimated GFR, with more average bias for 2009-CKD-EPI and less average bias for MDRD. eGFR by MDRD and 2009 CKD-EPI equation were more correlated with 51Cr-EDTA plasma clearance than 2012 CKD-EPI equation.
Overestimation was more significant when GFR>60 mm/min, it was especially more obvious in CKD-EPI cystatin C/Cr equation.
For GFR<60 ml/min, the bias was equal for all equations.
Other studies that have analyzed validity of MDRD and CKD-EPI equations in kidney transplantation, demonstrated controversial results and describe less or more bias with CKD-EPI compare to MDRD equation.
Changes in markers used for estimating GFR in kidney transplant circumstance can influence validity of these equations:
It should be taken in consideration that in kidney transplantation serum Cr have different relationship with GFR in contrast to non-transplanted patients for example steroids modify serum Cr/body mass ratio, although some authors concluded this effect is not significant when the patients are on long term low dose steroid.
Although cystatin C potentially is better marker than Cr for estimating GFR because it may less be influenced by age, gender, race and body mass (although some studies haven’t confirmed this), but in certain situation such as uncontrolled thyroid disease, rapid cell turn over, inflammatory state and in those under steroid therapy, it doesn’t correlate well with GFR. Cystatin C level may be raised in patients under high dose steroid therapy that is the case in kidney transplant recipients. Use of cystatin C in this study correlates with overestimation of kidney function, especially in the patients with higher GFR.
On the other hand, variety in substances and methods utilized in different studies for measuring GFR may impact on the validity of different equations, for example plasma clearance of 51Cr-EDTA provides higher value of GFR than the renal inulin clearance. In addition, in these studies, patients who were included were heterogeneous in age, gender, race, BMI, timing after kidney transplantation that modify validity and precision of the different equations.
In conclusion, it seems using MDRD-IDMS is more practical and accurate than CKD-EPI in kidney transplant setting.
This is a retrospective study. The level of evidence is 3.
In this article, 207 patients with kidney transplantation were studied one year after transplantation. Estimated GFR was calculated using different formulas such as MDRD, creatinine based and CKD-EPI cystatin-creatinine based. GFR was measured using 51 Cr-EDTA clearance. AII eGFRs by different formulas overestimated GFR (considering measured GFR).
. There are problems regarding Cockcraft- Gault method, such as higher weight not being a good indicator for higher muscle mass but might be duo to obesity. This formula is also not adjusted for BSA. There weren’t any enzymatic or standard method for measuring creatinine when this formula was introduced; hence, clearance of creatinine with this formula will be overestimated (about 10-40 %). MDRD formula is less accurate for obese people and in cases with near-normal GFR. To achieve this, it’s better to use CKD-EPI formula for estimating GFR when it is more than 60 ml/min. CKD-EPI formula gives a better GFR estimation compared to MDRD formula when the transplant patients have particularly higher GFR, BMI and are older. In diabetic patients, Asians, pregnant women and people with unusual body conditions like an amputation, these formulas are less accurate. Formulas that use both creatinine and cystatin-C are mostly prioritized, but since using steroid increases the amount of cystatin-C, the usage of cystatin-C formulas are limited in transplant patients. The best approach in monitoring kidney function after transplantation is combination of tracing serum creatinine, protocol biopsy in sensitized patients, detection of albuminuria or proteinuria and hypertension and screening of viral infections such as BK virus.
Thank you all for your contribution. Remember, the summary would be better in 250 words.
It is retrospective study , Level 3 evidence .
Summary
Glomerular filtration rate (GFR) estimation is very important to evaluate the kidney function in patients with or without kidney transplant.
Estimation may be through exogenous markers as inulin, iothalamate, 99mTc-DTPA or 51Cr-EDTA to directly measure GFR in kidney transplant . But unfortunately these techniques are very expensive and not always available , So many different formulas have been developed to estimate GFR depending on serum creatinine and cystatin C , inspite of their serum concentration
may be modified by factors other than GFR in kidney transplant patients.
The aim of this study is to processing the degree of agreement between the estimated GFR using the MDRD, CKD-EPI equations 2009 and the new equations CKD-EPI 2012 and also GFR measured by the plasma clearance of 51Cr-EDTA in renal transplant patients in a stable clinical condition.
270 patients – most of them had received cadaveric graft (89.6%) -were included and GFR was measured using 51Cr-EDTA in each patient. A 99.6% of patients were on prednisone (3.5-5 mg/day in 95% of the cases) when the GFR was measured.
Creatinine and cystatin c also were measured for all patients at the same time with estimation of ⁵¹Cr-EDTA (mGFR).
The study observed GFR is significantly overestimated in renal transplants patients using the MDRD-IDMS and the CKD-EPI equations of 2009 and 2012 as compared with the GFR measured as the plasma clearance with 51Cr-EDTA.
Equations used in estmating GFR:
Cockcroft–Gault (CG) formula : it depends on many variables as age, gender, weight and SCr In In Male = ([140 − age] × weight [kg])/(72 × SCr [mg/dL])
In Female: same as formula for male above × 0.85
Disadvantages :
This equation is overestimating CrCl in obese persons .
*Modification of Diet in Renal Disease (MDRD) Study:
Disadvantages :
Not validated in old age , pregnancy and children
Underestimate GFR in patients with GFR more than 60
Not accurate in non steady state as AKI
*Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI):
It is based on either s cr alone CKD EPI (creat) or Cystatin C alone CKD EPI ( cys) or both .
Has similar accuracy of MDRD when GFR less than 60ml/min/1.73m2 and better accuracy when GFR more than 60ml/min/1.73m2.
Other endogenous materials
Cystatin C : it is produced by all nucleated cells and 99% filtred by glomeruli and metabolized by proximal tubular cells .
In contrast to s Cr , Cystatin C not affected by body muscle mass , can detect AKI earlier than s Cr
But there is evidence of tubular secretion and extra renal metabolism ; thus, GFR may be over estimated, also it is altered in obesity ,DM , steroid use , lower serum albumin , malignancy
Cystatin C also not widely available and expensive
It is retrospective, case control study with level 3 evidence
In summary they did measure GFR for the 270 post transplant patients by injecting inulin substance and windrow the blood for test after 240 minutes and then compare the result by estimated GFR using the new CKD-EPI and MDRD formulas;they found that the ckd-epi formula over estimate the GFR and the MDRD more accurate in estimating GFR. Many studies compare those formulas with measured GFR with different substance and they found no much difference so they validate those formulas for estimating GFR.
The serum creatinine will give good reflection of graft function although they assume it was affected by steroid treatment
Retrospective study
level of evidence III
estimated GFR is crucial to follow up renal transplant recipients & patients with CKD
measured GFR using inulin, Cr EDTA or Tc-DPTA show that 40-72% of transplant recipients have GFR <60ml/min/1.73
different formulas are used to estimate GFR using serum creatinine and cystatin C
CKD-EPI of 2009 was more accurate than MDRD equation in young people, females and with normal creatinine level
CKD-EPI of 2012 included second marker, Cystatin C.
this study aimed to detect degree of similarity between estimated GFR using MDRD, CKD-EPI of 2009, of 2012 and measured GFR by Cr-EDTA in kidney transplant recipient during regular follow up
The results showed that in transplant patients only 50% of the change in GFR was detected by creatinine, serum cystatin C, sex and age
there is overestimation of kidney function when GFR calculated with these equations
Cystatin C is less affected by age, gender, race, body weight and muscle mass but it can be raised by high dose steroids without change in GFR
In kidney transplant recipients:
CKD-EPI of 2012 show greater bias than MDRD equation & measured GFR by Cr-EDTA.
eGFR >60ml/min/1.73m2: these equations significantly overestimate GFR
eGFR<30ml/min/1.73m2: MDRD equation is more accurate
In all stages of CKD: the degree of accuracy of all equations was low
monitoring graft functions:
patients should always be reminded that acute rejection rarely present with symptoms and signs
serum creatinine level should be measured regularly with estimation of GFR
Measurement of Cystatin C to provide more accurate estimate of GFR especially in patients with extremes of body weight and muscle mass
albumin excretion in urine should be checked at least once a year (persistent albuminuria >1gm for 6 months is associated with increased risk of graft failure)
II. Comparison of MDRD equations and the old equations CKD-EPI against new equations CKD-EPI in patients with kidney transplantation when used 51Cr-EDTA to measure glomerular filtration
TYPE OF ARTICLE:
Retrospective study (Case Controlled Study)
LEVEL OF EVIDENCE:
level III
SUMMARY:
Discussion of the best approach in monitoring graft function
Clinical monitoring & Laboratory:
1.This is a retrospective study
2.Level of evidence III
3.Measurement of GFR is essential for monitoring graft functions.
Serum creatinine which is the main measure of graft functions in clinical practice , is poorly correlated to GFR as it is affected by other factors as age sex muscle mass and tubular secretion
There also specific aspect is transplant patients ,effect of some drugs ( steroids ,trimethoprim ) on creatinine levels may lead to overestimating GFR in transplant patients
Measurment of GFR could be done directly , using exogenous markers as inulin and others
But with the direct Measurement of the GFR ,70% of patients found to have GFR less than 60 ml/Min.
Also being expensive and not available for practical use
This why there was a need to detect GFR in a different way and here came the idea of GFR estimation equations.
This study compared different equations used for GFR estimation , with direct measurement of GFR using plasma clearance Cr.EDTA
They concluded that all equations overestimates GFR when GFR is above 60 ml/min ,
But the error is reduced when GFR is below 30 ml/min ( with MDRD equation)
4. although MDRD equation has been released to replace prior equations to better estimate GFR, yet its performance in transplantation has been suboptimal .
Also in the non transplant population, the MDRD equation tend to underestimate GFR in patients with relatively good KFTs and this greatly affect patient management .
As a consequence, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation proposed recently by Levey et al. introduces a new equation for patients with low creatinine values
Several studies compared both equations In transplant population and found that both equations tend to overestimate GFR , but the bias is less with the MDRD equation .
Reference
Masson I, Flamant M, Maillard N, Rule AD, Vrtovsnik F, Peraldi MN, Thibaudin L, Cavalier E, Vidal-Petiot E, Bonneau C, Moranne O, Alamartine E, Mariat C, Delanaye P. MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients. Transplantation. 2013 May 27;95(10):1211-7. doi: 10.1097/TP.0b013e318288caa6. PMID: 23511243.
5. Best approach for monitoring graft functions according to KDIGO guidelines 2009 include
* urine volume
* albumin creatinine ratio
* serum creatinine
* Measurement of GFR using inulin iothalamate ,iohexol ,is the best methods for detection of GFR yet their use is limited because of their cost ,inavailbility and patient inacceptance
*Formulas to estimate GFR have been tested in transplant patients but no formula has been shown to be superior to any other formula. ( according to 2009 guidelines, but this has been further investigated, and there is more evidence that MDRD equation has some superiority in transplant population
* allograft US examination
* allograft biopsy .
kindly have a look at the equations in the attached picture
-1It is a case-control study.
– level of evidence 3
– It is a case-control study that includes 270 renal transplanted patients. Patient were over 18years old with stable kidney function. One year after kidney transplant, only 50% change in mGFR can detect by serum creatinine(S.cr) and cystatin C.Steroid used in kidney transplanted patients lead to modify serum creatinine/muscle mass. In this study, patients were on a very low dose of steroid so they could not analyze the discrepancy between GFR and S.creatinine.Cystatin C is a good marker for assessing GFR because does not affect by age, gender, body weight, and muscle mass but increases with a high dose of the steroid without the effect of GFR. Different equations were used to measure GFR that are MDRD-IDMS, CKD-EPI- Cr, CKD –EPI cystC and CKD-EPI-Cr+CystC but they show different results in many studies. this study observed overestimation of GFR by MDRD –IDMS, CKD-EPI Cr, and CKD-EPI Cr+CystC as compared with GFR measured as plasma clearance with 15Cr –EDTA.MDRD-IDMS has the highest sensitivity while CKD-EPI Cr+cystC has the highest specificity.
The limitation of this study cannot able to analyze the effect of steroid dose on GFR because of most of the patients are on a low maintenance dose of steroid.
-Serum creatinine, proteinuria, and renal ultrasonography are commonly used to monitor graft function. Some programs did surveillance kidney biopsies in selected patients such as highly sensitized patients
1- It is retrospective study.
2- Level of evidence III
3- Summary
Monitoring graft function post kidney transplantation is a very important yet difficult process as most of the currently used equations have their pitfalls , thus measured GFR (mGFR) with the clearance of an exogenous ideal marker such as Inulin, Iothalamate or Iohexol remains the gold standard method but it is not feasible clinical practice as the technique is invasive and expensive for routine use.
MDRD equations is derived CKD population , based on urinary clearance of Iiothalamate and affected by many variables including age, gender, race and S Cr. It tend to under estimate GFR specially in young , female patients and lower S Cr values .it is more accurate in patients with GFR < 60 mL/min/1.73 m .
While CKD Epi equation is derived from larger and more variable population including normal population , CKD, diabetic and solid organ transplant recipients .dependents on several variables as age,
Gende, race and S Cr . It is either based on SCr-alone CKD-EPI(creat) or cystatin C (cys)- alone CKD-EPI(cys) or combined SCr and cystatin C CKD-EPI(creat-cys)
In this retrospective study the authors compared the performance of MDRD and the 2009 and 2012 CKD-EPI equations with m GFR by 51Cr-EDTA plasma clearance in 270 kidney transplant patients one year post transplantation. They concluded that CKD Epi (creat-cys) tend to over estimate GFR in early CKD stages ( stage I and II) whith MDRD equation being more accurate in these stages .
4- For monitoring graft function , is better to comine several methods together including clinical assessment as BP and urine output , lab results as albuminuria , S Cr and e GFR by combined S Cr and Cyc based equation as CKD Epi ( Creat- CyC).
1- type of article : retrospective study
2- level of evidence :3
Summary
Monitoring graft function post kidney transplantation is a very important yet difficult process as most of the currently used equations have their pitfalls , thus measured GFR (mGFR) with the clearance of an exogenous ideal marker such as Inulin, Iothalamate or Iohexol remains the gold standard method but it is not feasible clinical practice as the technique is invasive and expensive for routine use.
MDRD equations is derived CKD population , based on urinary clearance of Iiothalamate and affected by many variables including age, gender, race and S Cr. It tend to under estimate GFR specially in young , female patients and lower S Cr values .it is more accurate in patients with GFR < 60 mL/min/1.73 m .
While CKD Epi equation is derived from larger and more variable population including normal population , CKD, diabetic and solid organ transplant recipients .dependents on several variables as age,
Gende, race and S Cr . It is either based on SCr-alone CKD-EPI(creat) or cystatin C (cys)- alone CKD-EPI(cys) or combined SCr and cystatin C CKD-EPI(creat-cys)
In this retrospective study the authors compared the performance of MDRD and the 2009 and 2012 CKD-EPI equations with m GFR by 51Cr-EDTA plasma clearance in 270 kidney transplant patients one year post transplantation. They concluded that CKD Epi (creat-cys) tend to over estimate GFR in early CKD stages ( stage I and II) whith MDRD equation being more accurate in these stages .
4-For monitoring graft function , is better to comine several methods together including clinical assessment as BP and urine output , lab results as albuminuria , S Cr and e GFR by combined S Cr and Cyc based equation as CKD Epi ( Creat- CyC).
It is a retrospective study with Level of evidence 3
Summary:
There are different equations for estimation of glomerular filtration rate in renal transplant patients, these equations and its accuracy is important to evaluate the transplanted kidney function.
CKD-EPI equations were superior to the MDRD study equation as the later showed systematic underestimation occurred in the GFR when applied to younger population, female sex, and lower serum creatinine levels.
This study which was carried out on 270 patients is analyzing the degree of agreement between the estimated GFR using the MDRD, CKD-EPI 2009 equations and the new equations CKD-EPI 2012 and the GFR measured by the plasma clearance of 51Cr-EDTA in kidney transplant patients in a stable clinical condition.
In the study; The estimated eGFR using the MDRD-IDMS and CKD-EPI-Cr equations was significantly higher than the mGFR, also The values of eGFR with CKD-EPI-CystC and CKD-EPICr + CystC were greater (p < 0.001) than the mGFR, being also greater than eGFR MDRD-IDMS
Also In the kidney transplant patients the GFR estimated by the CKD-EPI equations that use serum creatinine and cystatin C as markers of kidney function, show a greater bias than the MDRD-IDMS equation, and the GFR is measured by plasma clearance of 51Cr-EDTA as these equations produce a significant overestimation of the GFR if the eGFR is greater than 60mL/min/1.73m2, however the overestimation obtained is reduced with the MDRD-IDMS equation if the GFR is less than 30mL/min/1.73m2
Generally, Several studies in kidney transplants confirm the better performance of CyC-based equations over Cr-based equations in estimating GFR. The use of CyC alone or in combination with Cr is better as a predictor of graft survival and progression.
GFR estimation in kidney transplant and non transplant patients
The use of exogenous markers are expensive and not always available,so different formulas have been developed to estimate the kidney function in patients with CKD and in kidney transplant patients.
All equations overestimate GFR especially for CKD-EPI with creatinine and or cystatin c when GFR was greater than 60 ml/min/1.73m2.
The markers used for these these equations have been serum creatinine and cystatin c.
The serum concentration of these markers are modified by factors other than GFR in kidney transplant patients( age, gender ,race , drugs like steroids,trimethoprim, and hormones like thyroid hormone)
Cystatin c is better market than creatinine for assessment of GFR because it is less influenced by age ,gender ,race ,B.W or muscle mass
In this study 270 kidney transplant patients followed up after one year to analyze and compare the performance of the 4 equations (MDRD-IDMS , the 2009 CKD-EPI with creatinine, CKD-EPI with Cys., and the CKD-EPI with cr. And cys. 2012) against 51 Cr-EDTA plasma clearance in measuring GFR.
MDRD equation underestimate GFR when applied to younger population,female sex and lower S.cr levels .
So CKD-EPI equation with serum creatinine were developed to reduced this underestimation
The eGFR using the MDRD-IDMS and CKD-EPI-cr equations was higher than that the mGFR.
The value of eGFR with CKD-EPI cystatin c and CKD-EPI cr+cys.c were greater than that the mGFR.
Regarding validity of the different equations there is low bias with using CKD-EPI with GFR measurement
Other found greater overestimation of the GFR with CKD-EPI equation and less biases with the use of MDRD formula,and observed the CKD-EPI equation from 2012 has less bias than that the MDRD.
The authors concluded that the equation with cystatin c and cr. should not be used routinely but rather to confirm the existence of kidney failure.
In kidney transplants the S.cr has different relationship with GFR than non-transplant patients which causes overestimation of the actual kidney function calculated with these equations.
The MDRD-IDMS equation showed the highest sensitivity, while the highest specificity was obtained with CKD-EPI-cr+cyst.c equation.
GFR estimated by the CKD-EPI equations that use s.cr and cyst. C as marker of kidney function in transplant populations,showed a greater bias than the MDRD-IDMS equation and the GFR measured by plasma clearance of 51 Cr-EDTA.
These equations produce a significant overestimation of GFR if the eGFR is greater than 60ml/min/1.73m2
In all stages of CKD , the degree of precision with all the equations was low
The reference technique used to measure GFR in kidney transplants must be taken into consideration when analyzing the performance of the different MDRD-IDMS or CKD-EPI equations.
The article was original
The study is retrospective
Level of evidence was 3
Accurate estimation of GFR in transplant patient is very important to evaluate the function of the graft post transplant. Using exogenous factors as inulin, or 51Cr-EDTA may show accurate estimation of GFR , however their unavailability and high expenses make their use inapplicable. So, this retrospective study tried to find an equation correlate with the results of 51 Cr-EDTA in measuring GFR.
The study made comparison between MDRD, old CKD-EPI, and new CKD-EPI with 51 Cr-EDTA plasma clearance.
Creatinine as a biomarker is affected by age, sex, muscle mass, nutritional status, drugs as high dose steroids and trimethoprim.
In this study the effect of steroid may be abolished as most patients were receiving low dose steroids.
Cystatin C is less affected by age, sex, nutritional status if compared to creatinine
the study showed that all equations overestimate GFR in comparison to 51 Cr-EDTA plasma clearance method.
MDRD equation is better in estimation of GFR than new CKD-EPI in stage 1&2 CKD ( if GFR more than 60), but in patients with GFR less than 60 ml/min/1.73m2 MDRD is more sensitive and new CKD-EPI is more specific.
No equation showed accurate results in patients with BMI less than 20.
This original research article is retrospective study with level of evidence III.
Monitoring of the GFR is important aspect in the follow up of kidney transplanted patients.
This study compares eGFR estimated by the MDRD equation and CKD-EPI creatinine and CKD-EPI creatinine-cystatin equation with the GFR measured by 51 Cr-EDTA plasma clearance in kidney transplant patients.
Another research done at Mayo clinic comparing mGFR using iothalamate clearance compared with eGFR using MDRD equation , CKD-EPI Cr-Cystatin equation and CKD-EPI-Cystatin equation. The found the best equation to correlate with mGFR was MDRD equation , which underestimated mGFR by 2.2% , followed by CKD-EPI-Cr-Cystatin equation which underestimated mGFR by 8.1%, followed by CKD-EPI-cystatin equation which underestimated mGFR by 13.7%(1).
The serial measurement of serum creatinine is the most common way for monitoring graft function. The change in serum creatinine lags after the pathological injury(2).
Another way is to use protocol biopsies but it is not widely adopted , and it’s benefit is questionable , but it can be useful in certain situations ( highly sensitized patients , patients undergoing immunosuppression minimization) (2).
Monitoring for development of DSA also should be considered.
Measurement for proteinuria is an important aspect for graft function monitoring , raising levels may indicates an ongoing rejection or recurrence of disease(2).
BK virus screening also important to detect early infection to allow modification of immunosuppression before graft damage.
Measurement of blood pressure , blood sugar , body weight, tobacco use , lipid profile is necessary to allow for timely intervention to decrease the risk of graft injury.
References:
(1) Mira T. Keddis, Hatem Amer, Nikolay Voskoboev, Walter K. Kremers, Andrew D. Rule, and John C. Lieske Creatinine–Based and Cystatin C–Based GFR Estimating Equations and Their Non-GFR Determinants in Kidney Transplant Recipients
Clin J Am Soc Nephrol 11: 1640–1649, 2016. doi: 10.2215/CJN.11741115
(2) Michelle A. Josephson Monitoring and Managing Graft Health in the Kidney
Transplant Recipient
Clin J Am Soc Nephrol 6: 1774 –1780, 2011. doi: 10.2215/CJN.01230211
The article is retrospective , level 3 evidence .
-eGFR is used to estimate kidney function in CKD , and renal transplant patients .
There are different methods:
-270 kidney transplant recipients with stable graft function were enrolled in this study to compare the MDRD, CKD-EPI creatinine, CKD-EPI creatinine + cystatin c equations to 51 cr-EDTA in assessing the eGFR.
-All of the patients were on low dose steroids, above 18 years ,one year post transplant and most of the participants received deceased donor kidney.
-Measured GFR correlated significantly with serum creatinine and cystatin c.
– eGFR using CKD-EPI-cystatin and creatinine and cystatin were higher than measured GFR
– eGFR using MDRD and CKD-EPI-cr were higher than measured GFR by cr-EDTA
– MDRD showed more sensitivity compared to CKD-EPI cr+cyst for eGFR <60
-All equations overestimated GFR.
-Creatinine itself is an unreliable index for graft function as it varies according to age, sex, nutrition status, race, muscle bulk, moreover GFR can decline before the serum creatinine rise.
-In renal transplant patients with higher GFR the preferred equation is MDRD .
This article is a retrospective study with level evidence of 3.
In this article, the authors evaluated the EDTA clearance and compared it to the standard equation of estimated GFR (eGFR). the CKD-EPI equation was developed to reduce the underestimation of MDRD equations. measuring the clearance by EDTA, DTPA, or inulin, etc. is impractical not easily attainable. the estimated GFR was higher compared to the measured GFR. ın transplant patients there was a discrepancy of resultıs among different studies. some hypothesized this was due to drugs like steroids and the ratio of muscle mass others did not. In this study, this was not evaluated as all patients had very low steroid intake. cystatin c appears to be less affected by age, gender, muscle mass, race e.g.
For monitoring graft function it is good to do serial evaluations of eGFR, kreatinin and may be 24-hour urine collection and correlating with that. In transplant patients, creatinine could be affected by drugs especially in the first 6-12 months post-transplant. Cystatin maybe valuable but may not be easily available in some laboratories. correlation with protocol biopsies in selected cases may be reasonable
1-retrospective cohort study.
2-level of evidence 2
3-The MDRD eGFR equation and the 2009 CKD-EPI equation have a stronger correlation with 51Cr-EDTA than CKD-EPI with creatinine and/or cystatin C.
When GFR was larger than 60ml/min/1.73m, the overestimations were inversely linked with creatinine and cystatin C levels, most substantially for CKD-EPI with creatinine and/or cystatin C when GFR was greater than 60ml/min/1.73m.
the GFR measured by the CKD-EPI equations, which employ serum creatinine and cystatin C as indices of renal function, has a larger bias than the MDRD-IDMS equation, which measures GFR by plasma clearance of 51Cr-EDTA.
If the eGFR is larger than 60mL/min/1.73m2, these equations create a considerable overestimation of the GFR; however, if the GFR is less than 30mL/min/1.73m2, the error achieved is lowered below that found with the MDRD-IDMS equation. In all phases of CKD, the degree of accuracy with all equations was poor.
When comparing the performance of the several MDRD-IDMS or CKD-EPI equations, it’s vital to consider the reference approach used to quantify GFR in kidney transplants.
This is a retrospective study.
Level of evidence: 3.
The estimation of glomerular filtration rate (GFR) is essential to evaluate kidney function in patients with kidney transplant. Measured GFR using exogenous markers such as inulin, iothalamate, 99mTc-DTPA or 51Cr-EDTA remains the gold standard for assessment of renal graft function, however this method is not always feasible or available. The objective of the study in this article is to analyze the degree of agreement between the estimated GFR using the MDRD, CKD-EPI equations 2009 and the new equations CKD-EPI 2012 and the GFR measured by the plasma clearance of 51Cr-EDTA in kidney transplant patients in a stable clinical condition.
The study in this article observed a significant overestimation of GFR in kidney transplants patients using the MDRD-IDMS and the CKD-EPI equations of 2009 and 2012 as compared with the GFR measured as the plasma clearance with 51Cr-EDTA. All equations overestimate eGFR comparing to mGFR.
In patients with GFR more than 60ml/min/1.73 m2, MDRD equation was shown to be more reliable and more sensitive , while CKD-EPI-Cr + CystC equation is the most specific.
MDRD equation was more reliable for classification of CKD into stage 1 and 2 where creatinine and cystatin C based CKD-EPI was more reliable in more advanced kidney disease.
Estimation equations were not accurate in patients with BMI< 20.
Serial measurement of serum creatinine with the proper use of eGFR equations as MDRD and CKD-EPI may be the best method of monitoring renal functions after transplantation
It’s a retrospective study that used MDRD and old CKD _ EPI equations against 51Cr_EDTA plasma clearance in 270 kidney transplant patient after one year .
Serum creatinine is the main marker that used widely till now to estimate the GFR in practice but it’s affected by factors that make the relationship between S.creatinine and GFR is difficult especially posttransplant and the main factor is using of prednisolone that affect on
muscle mass .
Another marker that used in this study is cystatin c which is more preferable for measuring GFR because it’s less affected by muscle mass ,age sex ,race but it’s level is high in patients on steroids .
The study showed that MDRD equation has is more sensitive but less specific than CKD _EPI
A) Type of Article: It is a retrospective study
B) Level of evidence provided by the article: Level III
C) Summary:
The study was conducted retrospectively with an aim to compare the glomerular filtration rate (GFR) of transplant recipients measured using 51Cr EDTA plasma clearance and various equations used to calculate GFR (MDRD, CKD-EPI 2009 and CKD-EPI 2012 equations). The measurement of the GFR was done at one year post-transplant.
The study was conducted at a single center. All the patients were aged above 18 years. A total of 270 subjects were finally assessed. GFR was measured using plasma clearance of 51Cr-EDTA and same days blood samples were taken for serum creatinine and serum cystatin C.
The mean measured GFR (mGFR) was 43 ml/min/1.73 m2. The mean creatinine value was 1.42 mg/dl and mean cystatin value was 1.45 mg/dl.
mGFR <60 ml/min/1.73 m2 was seen in 91.9% of the patients. The corresponding value was 67%, 56.3%, 61.1% and 57.8% using MDRD, CKD-EPI-Creatinine, CKD-EPI-Cystatin C and CKD-EPI-Creatinine+CystatinC equations.
So, all the equations over-estimated the GFR values, but least overestimation seen with MDRD and 2009 CKD-EPI equations.
For detecting GFR<60, MDRD equation was most sensitive while CKD-EPI-Creatinine+CystatinC equation was most specific.
The study was done in a homogeneous group, whereby all the samples were taken at one year post-transplant (which was not done in previous studies published) but the effect of steroids could not be analyzed as majority of the patients were on steroids.
D) Various equations used in transplant patients to evaluate GFR include
MDRD
CKD-EPI Creatinine
CKD-EPI Cystatin C
CKD-EPI Creatinine+Cystatin C
Nankivell equation
Lund Malmo Revised
Full Age spectrum equation
And a few more have been evaluated.
Xiang He et al, in their study, used equations for eGFR to evaluate whether it could oredict mortality and graft failure. Their study did not show much utility for eGFR in predicting the same. (1)
None of the equations have been shown to be closely following the measured GFR and hence there is no standard/ consensus developed to use these equations for calculating GFR in the transplant recipients.
E) Serum creatinine is a very cheap and reliable test available which can be utilized for follow-up of a transplant recipient.
For follow-up of graft function, a combination of Clinical and laboratory parameters are important: Blood pressure, serum creatinine, proteinuria, ultrasound graft kidney, 24 hour urine creatinine clearance and kidney biopsy (protocol or indication based)
References:
1) Xiang He, Jason Moore, Shazia Shabir, Mark A Little, Paul Cockwell, Simon Ball, Xiang Liu, Atholl Johnston, Richard Borrows. Comparison of the predictive performance of eGFR formulae for mortality and graft failure in renal transplant recipients. Transplantation 2009;87:384-92.
This is a retrospective study- original article with level of evidence III.
SUMMARY
Measured GFR using exogenous markers such as inulin, iothalamate, 99mTc-DTPA or 51Cr-EDTA remains the gold standard for assessment of renal graft function, however this method is not always feasible or available, in addition to high cost. So estimation of GFR is considered to substitute the mGFR.
Many formulas have developed to estimate GFR based on endogenous markers like creatinine and cystatin C. But studies showed that when estimating GFR in kidney transplants, there were significant differences between m-GFR and e-GFR.
CKD-EPI equations in 2009 and 2012 were developed to correct the underestimation of GFR by MDRD although different categories of population were included.
e-GFR equations were not recommended for routine use, but to confirm the existence of kidney failure as concluded by the authors.
In this retrospective study, 270 patients with kidney transplant mostly from cadaveric donors underwent measurement of GFR using 51Cr-EDTA and estimation using the following formulas: eGFR MDRD, eGFR CKDEPI-Cr, eGFR CKD-EPI-CystC and CKD-EPI-Cr +CystC.
All equations overestimate eGFR comparing to mGFR.
In patients with GFR more than 60ml/min/1.73 m2, MDRD equation was shown to be more reliable and more sensitive , while CKD-EPI-Cr + CystC equation is the most specific.
MDRD equation was more reliable for classification of CKD into stage 1 and 2 where creatinine and cystatin C based CKD-EPI was more relianle in more advanced kidney dieases.
Estimation equations were not accurate in patients with BMI< 20.
Thank you All for your excellent contributions. I hope the rest join us. Remember, you need to achieve 75% contributions. Many of you still lagging behind.
the article is retrospective study with level of evidence 2
eGFR used to estimate kidney function in CKD , and renal transplant patient
there are different methods:
1- Direct measure eGFR using inulin or cr-EDTA but still unavailable and expensive.
2- So, other methods like equations were used:
a- MDRD
b- CKD-EPI use creatinine
c- CKD-EPI use cystatin C
d- CKD-EPI use creatinine and cystatin C
3- There is some limitations also to these equations due to overestimation or underestimation at different levels of GFR
4- 270 patients were included in the study, GFR by cr-EDTA, serum creatinine and cystatin C were measured (most of the patients received cadaveric graft and most of them on prednisolone, which increased the level of cystatin C and affects muscle which affected serum creatinine also).
5- Measured GFR correlated significantly with serum creatinine and cystatin c
6- eGFR using MDRD and CKD-EPI-cr were higher than measured GFR by cr-EDTA
7- GFR using CKD-EPI-cystatin and creatinine and cystatin were higher than measured GFR
8- Therefore, equations will overestimate GFR at certain levels.
9- No standard available and accessible method to estimate truly GFR until now.
Q1- retrospective study
Q2- level of evidence 3
Q3- two hundred seventy kidney transplant recipients (1 year post transplant) with stable graft function & more than 18 years old were enrolled in this study to compare the performance of MDRD, CKD-EPI creatinine, CKD-EPI creatinine + cystatin c equations to 51 cr-EDTA.
All of the patients were on low dose steroid and the majority were male, most of the participants received deceased donor kidney. mGFR was 43+- 11.
study findings:
1.there is a significant correlation between mGFR and creatinine, also significant correlation between mGFR and cystatin c.
2. eGFR measurement by MDRD and CKD-EPIcreatinine was higher than mGFR.
3. eGFR measurement by CKD-EPIcyst.c , CKD-EPI cr+cyst.c was higher than mGFR and also higher than MDRD.
for eGFR <60 , MDRD showed more sensitivity and somewhat lower specificity compared to CKD-EPI cr+cyst.c.
All equations overestimated GFR with a different bias levels
if BMI is less than 20, all equations did poorly
eGFR by MDRD and CKD-EPIcr correlated better with 51cr-EDTA
the strength of this study is that all the GFR was measured 1year post transplantation in all of the participants while in other studies they include people with different times from transplantation
limitation of this study is that it was unable to show the effect of steroid on GFR as all the participants were on low dose steroid.
Q4&5. measuring GFR using exogenous substances such as inulin, iohexol, iothalamate,51cr-EDTA, 99Tc-DTPA is more accurate than the use of endogenous substances such as creatinine and cystatin C ,, it is well known that creatinine has different relationship to GFR in kidney transplant than in non-transplant patients, in the early post transplant period, there will be a rapid drop in serum creatinine level so it is unwise to depend on it for the evaluation of GFR,, in addition the use of steroid can can affect creatinine level as steroid change the serum creatinine/ muscle mass ratio and may cause discrepancy between serum creatinine and kidney function, also cystatin c level is affected by steroid treatment.
the use of trimethoprime for prophylaxis can reduce creatinine secretion and gives a false impression of low GFR.
Thank you All
Yes, retrospective, level 3 evidence. Well done
Excellent contribution, but some of you copied and pasted from the article. You need to read it and summarize it.
It is an original article about retrospective study
Level III (retrospective controlled) According to oxford system for evidence level
Summary
The estimation of glomerular filtration rate (GFR) is essential to evaluate kidney function in patients with kidney transplant. The use of exogenous markers as inulin, iothalamate, 99mTc-DTPA or 51Cr-EDTA to directly measure GFR in kidney transplant show that about 40-72% have a GFR < 60 mL/min/1.73 m2. These techniques are expensive and not always available for monitorization of kidney function. This is the reason why different formulas have been developed to estimate with sufficient precision the kidney function in patients with chronic kidney disease (CKD) and in kidney transplant patient. The markers chosen to develop
these equations have been serum creatinine and cystatin C ; the serum concentration of these substances may be modified by factors other than GFR in kidney transplant patients.
The objective of the study in this article is to analyze the degree of agreement between the estimated GFR using the MDRD, CKD-EPI equations 2009 and the new equations CKD-EPI 2012 and the GFR measured by the plasma clearance of 51Cr-EDTA in kidney transplant patients in a stable clinical condition.
There were 270 patients included in the study and each patient had the measurement GFR using 51Cr-EDTA. A 99.6% of patients were on prednisone (3.5-5 mg/day in 95% of the cases) when
the GFR was measured. Most patients had received cadaveric graft (89.6%). Steroids modify the serum creatinine/muscle mass ratio and may cause a discrepancy between serum Cr levels and
kidney function, however other factors may be involved. Some studies indicate that in patients not taking steroids there is less overestimation of GFR however this effect is not that evident with time after transplantation.4 Other authors have failed to show an effect of steroids and some authors consider that the low dose of steroids used in long-term patients should not have an effect on serum creatinine/muscle mass ratio.
The study in this article observed a significant overestimation of GFR in kidney transplants patients using the MDRD-IDMS and the CKD-EPI equations of 2009 and 2012 as compared with the GFR measured as the plasma clearance with 51Cr-EDTA.
The glomerular filtration rate is usually estimated (eGFR) by formulas such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD). When serum creatinine is not in a steady state, estimation of the GFR using conventional formulas is unreliable and lags behind the true underlying GFR. Due to the rapid decrease in creatinine concentration after RTX, conventional formulas do not accurately estimate GFR .
Several dynamic renal function formulas (DRFFs) have been developed to estimate renal function during acute fluctuations of serum creatinine concentration. These DRFFs are based on the pharmacokinetic principles of creatinine mass balance; when creatinine production exceeds excretion, creatinine will build up in the volume of distribution until excretion again equals production and a new steady state has been reached, or vice versa
Assessment of glomerular filtration rate (GFR) is important in the follow-up of patients after receiving a kidney transplant. Many equations based on plasma markers are in use for estimating GFR in different patient groups, but there is still a need for a specific and accurate equation for use in kidney transplant recipients. Several equations are based on the endogenous substance creatinine. It is well known that the plasma level of creatinine is affected by muscle mass and ingestion of protein or creatine, in addition to the GFR. Plasma creatinine is also somewhat limited as a marker for GFR since it is subjected to a certain degree of tubular secretion
The endogenous protein cystatin C has also been used as a marker for renal function with the advantage that it is less dependent on muscular mass. Thus, cystatin C can be used as an alternative, or incorporated as an auxiliary marker, for estimating GFR in patients with low muscle mass (children, elderly, patients with anorexia, amputations, or paresis) or high muscle mass (bodybuilders). Cystatin C is also less influenced by renal tubular secretion and may be a good alternative to creatinine-based equations in situations where tubular excretion of creatinine is affected (eg, drugs blocking the tubular creatinine transporter such as trimethoprim).
However, different studies have reported that cystatin C could be influenced by factors independent of GFR, such as the level of corticosteroids, thyroid hormones, sex, diabetes, and inflammation. On the other hand, one study claims that the inflammatory status of a patient does not influence cystatin C levels. If a more accurate determination of GFR is needed, an exogene marker should be used, such as clearance of the nonradioactive substances, like the contrast agent iohexol or inulin or radiolabeled agents, like 51Cr-ethylenediaminetetraacetic acid (51CrEDTA), 99mTc-diethylene-triamine-pentaacetate (99mTcDTPA) or 125I-iothalamate, but these techniques are invasive, time consuming and costly.21
The CKD-EPIcreatinine+cys C formula is superior to the CKD-EPIcreatinine equation
However, monitoring of graft function doesn’t depend on eGFR only but we need to monitor other parameters; urine volume is important to monitor graft function and urine test for proteinuria
This is a retrospective study.
Level of evidence: 3
In this retrospective study, the authors aimed to estimate the bias and accuracy of different equations for estimated GFR against the standard measured GFR by the radiolabeled tracer in kidney transplant patients.
They selected patients who have at least one measured GFR using 55Cr-EDTA and both creatinine and cystatin C measurement at the same time. Then they used the latter two to get estimated GFR and then compare the accuracy and bias in all GFR categories.
Among the 270 analyzed patients, nearly 92% had measured GFR < 60 ml/min/1.73 m2. MDRD equation was the most sensitive and 2nd specific in comparison to other equations in estimation of GFR.
The authors’ finding is not in concordance with other studies where the CKD-EPI equation was the most accurate method for eGFR detection. They attributed this difference to both differences in measurement tools, having the majority of patients with mGFR < 60 ml/min/1.73m2 and to different populations, as most other studies usually attribute their differences.
Different radiolabelled isotope tracers have been used for the validation of eGFR equations. Such tracers include 99mTc-DPTA, 51Cr-EDTA, or other markers iothalamate and inulin.
The persistent issues with the applicability of such markers are the high cost and technicalities making them unfeasible for most transplantation centers worldwide.
Serial measurement of serum creatinine with the proper use of eGFR equations as MDRD and CKD-EPI may be the best method of monitoring renal functions after transplantation.
-This article is an original research
-The level of evidence is III
-The exogenous markers as inulin, iotha[1]lamate, 99mTc-DTPA or 51Cr-EDTA used to measure GFR directly in kidney transplant showed that most of patients have a GFR < 60mL/min/1.73m2,but due to being unapplicable; other equations were established to be mor practical.
CKD EPI creatinine equation 2009 was done to overcome the underestimation of GFR with MDRD equation in some population ;(female ,low creat ,adolesecents).
Meanwhile CKD EPI Creat + Cystatin C equation 2012 was developed revealing only slight improvement in the estimation of GFR compared to others
The studies done was not much conclusive as some showed that CKD EPIcreat 2009 showed more bias than MDRD in estimating GFR in renal transplant in comparison to CKD EPI creat+cystatin C 2012 which was less biased than MDRD.
This study compared the concordance between the estimated GFR using the
-MDRD,
-CKD-EPI 2009 ,
-CKD-EPI 2012
-by measuring the plasma 51Cr-EDTA clearance in stable kidney transplants
It was found that the overestimation of GFR obtained by CKD-EPI-Cr equation bias was more than that obtained with MDRD-IDMS equation in the different CKD stages, this bias was more evident in the group with mGFR ≥60mL/min/1.73m2 ;
MDRD-IDMS classified correctly in stages 2 and 3 while CKD-EPI-Cr +CistC or CKD-EPI-CistC were more accurate for classifying of CKD stage 4.
Stevens et al.19 stated that the bias was lower with CKD-EPI 2009than with MDRD-IDMS formulas, with insignificant dif[1]ferences between transplanted and non-transplanted.
It was observed that the MDRD-IDMS equation was more sensi[1]tivite, while CKD-EPI-Cr +CystC equation was more specific
It was concluded that estimation of GFR in renal transplants correlated with diverse number of risk factors .
-Monitoring graft function through
.serial serum creat measurement despite its affection by multiple factors as steroids,thyroid hormone and trimethoprim,
. as well as cystatin C measurement
Studies showed that measuring both serum creat and cystatin C together represents e GFR better than serum creat alone
.24 h urinary creat clearance , inulin,iothalamte and iohexol clearance which is more accurate than creat in assessinh graft function but it is expensive
.e GFR using different equations which was not recommended by KDIGO
.urinary biomarkers and urinary protienuria
.Renal biopsy specialy in highlysensitised recipents
.Renal scintigraphy to asses structure and blood flow
Dear All
Thank you for working hard, but my advice, you need to do your search before answering the question.
See the diagram below and give us an answer about the type of this study and its level of evidence:
According to the diagram l, level of evidence is III as it is a retrospective study.
1. What is the type of the article?
Retrospective study
2. What is the level of evidence this article provides?
Level of evidence III
retrospective study with level 3 evidence
reterospective study , level of evidence 2
Depend on the diagram , It is a retrospective study , level of evidence is III .