2. A 66-year-old CKD 5 secondary to IgA nephropathy received a suitable kidney offer from his brother. He gave a history of retention of urine 6 months before commencing dialysis. He became anuretic since he started dialysis
- Any special consideration regarding this past medical history?
The past history should analyze the relevant given history….He is a 66 year old with history of retention of urine. .This could be due to bladder outlet obstruction…The most common reasons are BPH, detrusor sphincter dyssynergia due to neurological disorders, Diabetic cystopathy (patient is not a diabetic), stricture urethra due to previous catheterization….A full evaluation with PVR, uroflowmetry and urodynamic study maybe needed in the pre operative period. .If there is significant bladder outlet obstruction, that needs to be assessed and surgery has to be done….There could be an increased risk of UTI post transplant if these are not corrected….
The next factor in the past history is IgA nephropathy itself which can cause recurrence of the disease is about 25 – 30%..The risk factors for recurrence include male gender, rapidly progressive IgA, uncontrolled hypertension in pre transplant, early steroid withdrawal….
The patient already has a kidney disease that would lead to CKD, but it seems to have evolved in an acute form of urine. This draws attention to the need to exclude any obstructive factor, mainly due to prostate enlargement, as it would be necessary to exclude prostate cancer.
Therefore, it would be important to perform an imaging exam and subsequently conduct a biopsy if necessary.
66 year old patient on Hdx , with history of urine retention and Anuria .
He requires full detailed history , full abdominal examination , urine examination , ultrasound abdomen and pelvis , serum PSA , As well as Urodynamic studies .
Based in his age , the most common cause is BPH after Exclusion of prostatic carcinoma . And he may require TURP +_ prostate biopsy .
Regarding the original renal disease which is IgA nephropathy.
Recurrence rate is about 25 to 30 %
Risk factors for IgA Recurrence are RPGN , high level of IgA above 200 mg/dl , early Steroid withdrawal post Tx , male gender
If Recurrence of IgA post Tx
Tight BP control using ACE-I , Steroids if proteinuria more than 1 gm
The native kidney disease being IgA nephropathy requires special attention, as there is chances of recurrence hence patient and his brother should be counselled.
Regarding his h/o urinary retention, all causes of retention should be looked at and treat if possible before surgery including.
1. Outflow obstruction due to mechanical factors (narrow urethral channel) and/or dynamic factors (increased muscle tone within and around the urethra). Benign prostatic hyperplasia (BPH). Other causes of outflow obstruction in men include constipation, prostate or bladder cancer, urethral stricture, urolithiasis.
2. Neurologic impairment : interruption of the sensory or motor nerve supply to the detrusor muscle. Incomplete relaxation of the urinary sphincter mechanism.
3. Spinal cord injuries from trauma, infarct or demyelination, epidural abscess and epidural metastasis, Guillain-Barré syndrome, diabetic neuropathy, and stroke.
4. Inefficient detrusor muscle
5. Medications – Multiple medications are implicated as a cause of urinary retention; most common among these are the anticholinergic and sympathomimetic drugs.
1. Infection –such as acutely inflamed prostate gland from acute prostatitis , a urinary tract infection can cause urethritis and urethral edema . Genital herpes may cause local inflammation as well as sacral nerve involvement. Other infections include varicella zoster. Transverse myelitis attributed to Lyme disease. 2 days after herpes zoster lesions in the sacral dermatomes (S2-S4) resulting in reversible bladder dysfunction
6. Trauma – Patients with trauma to the pelvis, urethra, or penis.
There are few case report about unusual causes of acute urinary retention such as:
· mechanical obstruction to bladder emptying could be due to:
1. Severe urethral inflammation
2. Chronic lymphocytic leukaemia infiltrating the prostate,
3. Staphylococcal prostatic abscess
· Bladder overdistension due to tumour arising from within a giant bladder diverticulum which presented as an abdominal mass (case report)
· Increased sphincter tone:
1. Neurofibromatosis in the bladder neck and prostate causing increased tone in external sphincter.
2. After anorectal surgery; thought to be due to increased sphincter tone
· Interference with sensory or motor innervation Due to the bladder Diabetic cystopathy
· After intense anal intercourse
The patient has to be evaluated by:
· History and Physical examination including Rectal examination
· Bladder ultrasound, bladder ultrasound
· Neurologic evaluation – The neurologic examination should include assessment of strength, Sensation, reflexes, and muscle tone.
· Laboratory studies – A urine sample should be obtained and sent for urinalysis and urine culture.
· Check a prostate-specific antigen (PSA)
· You might need to do cystography/ cystoscopy and uroflow.
References
Mark Emberton, Ken Anson. Acute urinary retention in men: an age old problem. BMJ 1999;318:921
uptodate
Clinical recurrence rates for IgAN in grafts are around 30%, and histological recurrence rates (which include cause and protocol biopsy) are even higher at more than 50%. Before the transplant is performed, this needs to be explained.
The history of retention initiates the workup for the lower urinary tract obstruction, which includes:
2. A 66-year-old CKD 5 secondary to IgA nephropathy received a suitable kidney offer from his brother. He gave a history of retention of urine 6 months before commencing dialysis. He became anuretic since he started dialysis
The risk of recurrence may be higher among recipients of living-related-donor kidneys, compared with deceased-donor kidneys, but there is no basis for avoiding a living-related-donor source. HLA specificity may affect the likelihood of recurrent IgAN, with the presence of either HLA-B35 or HLA-DR4 increasing the risk in some. In a study of 86 kidney transplant recipients with a history of IgAN, the risk of IgAN recurrence was decreased among those who had an HLA-B full mismatch with their donor, compared with those who had at least a one HLA-B match. A registry study of 1354 patients with end-stage disease due to IgAN from Australia and New Zealand showed that zero-HLA-mismatched living-donor recipients were more likely to develop recurrence than the whole cohort of living and deceased donors. Conversely, a Korean study found no association with full HLA match and the risk of recurrent IgAN among patients with IgAN.
Certain factors are associated with recurrence:
1-Early withdrawal of glucocorticoids from the maintenance immunosuppression regimen after kidney transplantation may be associated
2-An increased serum IgA concentration
3- Elevated Galactose-deficient IgA1-specific IgG autoantibodies
4-Rare genetic variants in CFHR5
5-Younger Recipient age (1)
Regarding the urine retention:
This patient need urological evaluation before transplantation in form of imaging and dynamic studies .Urodynamic evaluation can often reveal significant pathology. Treatment options are widely variable, from observation to reconstructive surgery, and should be based on the patient and urodynamic findings.(2) The incidence of urological malignancies like renal cell carcinoma, urothelial cancer of the bladder, and penile carcinoma is increased following RT, while the incidence of prostate and testis cancer is the same as in the nontransplant population. Surgical and nonsurgical treatment options do not differ from the normal population. Adaptation, cessation, or switching of the immunosuppressive regimen in case of urologic malignancy must be decided on the individual recipient basis.(3) Graft survival and functions after renal transplant were not significantly different between patients with abnormal and normal bladders over at least the first 10 years. Therefore, it is safe to transplant into abnormal bladders once they have been assessed, reconstructed if necessary, and managed appropriately (4)
1- Up to date
2- Rude T, Nassiri N, Naser-Tavakolian A, Ginsberg D. The Role of Urodynamics in the Pre-transplant Evaluation of Renal Transplant. Curr Urol Rep. 2019 Apr 5;20(5):26. doi: 10.1007/s11934-019-0887-3. PMID: 30953228
3- Giessing M. Urologische Nachsorge und Entwicklung von Malignomen nach Nierentransplantation [Urological follow-up and development of cancer after renal transplantation]. Urologe A. 2015 Oct;54(10):1393-401. German. doi: 10.1007/s00120-015-3910-4. PMID: 26459582.
4- Salman B, Hassan A, Sultan S, Tophill P, Halawa A. Renal Transplant in the Abnormal Bladder: Long-Term Follow-Up. Exp Clin Transplant. 2018 Feb;16(1):10-15. doi: 10.6002/ect.2016.0193. Epub 2017 Jul 31. PMID: 28760118.
Any special consideration regarding this past medical history?
patient has ESRD due to IgA nephropathy .
The patient should be counselled about the risk of recurrence of IgA nephropathy in the graft.
The reported frequency of histologic or clinically significant recurrence of IgAN varies in the reported literature, with the incidence probably increasing as a function of time from transplantation.
In the multicenter Post-Transplant Glomerular Disease (TANGO) cohort study of 504 transplant recipients with biopsy-proven IgAN as the cause of end-stage kidney disease , the cumulative incidence of recurrence was 19 percent at 10 years and 23 percent at 15 years.
Among patients with recurrent IgAN, the median time to recurrence was 3.4 years.
– risk factors for recurrence includes:
living related donor ,younger age at renal transplantation, rapid course of renal failure, increased number of HLA mismatch living donor,.
Female patients had more than twice the risk of IgAN recurrence within the first year after transplantation compared to male patients.
high Serum concentrations of total IgA.
This patient is a male and has received an offer from a living related donor no data about HLA mismatch but still there is a risk of recurrence.
History of urinary retention:
the patient had history of urinary retention 6 months before dialysis and now he is an-uric , he needs full urological examination to detect the cause
and the evaluation must includes
– abdomen and pelvis ultrasound to assess prostate ,stones, any abnormality in urinary tract.
-CTUT
-total and free PSA
-cystoscopy
according to his age he might have BPH , but he is still at risk for prostatic cancer
If it is due to marked BPH, then TURP can be done.
prostatic carcinoma to be treated according to stage with urological consultation about when to be suitable for transplantation.
reference
Andresdottir MB, Haasnoot GW, Doxiadis II, et al. Exclusive characteristics of graft survival and risk factors in recipients with immunoglobulin A nephropathy: a retrospective analysis of registry data. Transplantation 2005; 80:1012.
Koch MJ. Considerations in retransplantation of the failed renal allograft recipient. Adv Chronic Kidney Dis 2006; 13:18.
Choy BY, Chan TM, Lai KN. Recurrent glomerulonephritis after kidney transplantation. Am J Transplant 2006; 6:2535.
Uffing A, Pérez-Saéz MJ, Jouve T, et al. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Clin J Am Soc Nephrol 2021; 16:1247.
IgA nephropathy generally returns a few years after transplantation, according to recent research, and extended follow-up studies revealed poorer survival rates after 5–10 years. In studies with medium follow-up, reported graft loss owing to recurrent IgA nephropathy ranges from 2% to 14%, but in studies with long follow-up, it rises to 29% in patients with symptomatic recurrent illness
The incidence of IgA nephropathy recurrence increased gradually after transplant with a cumulative incidence of 19% at 10 years, and 23% at 15 years) after kidney transplantation.
Risk factors for recurrence:
Higher HLA-mismatch,
earlier steroid discontinuation
transplant without an induction agent
younger age at transplant
Hx of urine retention :
Excluding of benign prostatic hyperplasia or prostatic cancer or Prostatitis
uretheral stricture
UB cancer , infection , Detrusor sphincter dyssynergia
Atonic bladder ( in marked autonomic neuropathy )
So PA US , CT UT , Ascening CUG , Urodynamics and even cystoscopy may be needed
tumor markers PSA Total and free , urine analysis and urine CS may be needed
MRI of the lumbar spine should be considered ( if neurogenic causes is suspected )
Ref :
Marinaki S, Lionaki S, Boletis JN: Glomerular disease recurrence in the renal allograft: A hurdle but not a barrier for successful kidney transplantation. Transplant Proc 45: 3–9, 2013
Kowalik, Urszula; Plante, Mark K. (June 2016). “Urinary Retention in Surgical Patients”. The Surgical Clinics of North America. 96 (3): 453–467.
According to IgA, the patient should be counselled about risk of recurrence after kidney transplantation, the recurrence rate of IgA is 21% to 58%.
Risk factor for recurrence (Use of living-related-donor kidney,specific human leukocyte antigen (HLA) alleles in recipient including HLA-B35, HLA-DR4, HLA-B8, HLA-DR3,
good HLA match between donor and recipient,Glucocorticoid withdrawal,high serum IgA concentration,elevated galactose-deficient (Gd)-IgA1-specific immunoglobulin G (IgG) autoantibodies and young recipient age.
According to history of urine retention
causes of urine retention include
1.Outflow obstruction caused by BPH,prostate and bladder cancer,urethral stricture and urolithiasis,
2.Neurological impairment ( spinal injuries,stroke,diabetic neuropathy)
3.Medications ( anticholinergic and sympathomimetic drugs
4.Infection(prostatitis,urethritis)
5.Trauma to pelvis or urethra.
Workup for history of urine retention
History
Physical examination includes rectal examination(PR).
Post voiding residual urine ,urine analysis, voiding cystourethrogram and urodynamic studies cannot be done as the patient is anuric,
CT , Ultrasound,X ray.
Cystoscopy
There are two issues which are pertinent to this case
Recurrence of IgA Nephropathy and significant history of urinary retention before hemodialysis.
Recurrence of IgA nephropathy is 40-60% post-transplant and factors like young recipient age and getting live donation ,having HLA specificity i.e.,B35 or HLA-DR4 matching and early steroid withdrawal increase the risks. However, graft loss is less than 10 percent.
Patient with history of urinary retention should be thoroughly evaluated by urologist before renal transplant to rule out possible causes of bladder outflow obstruction like carcinoma prostate or BPH, urinary tract infection, recurrent stone formers, neurogenic bladder , reflex nephropathy, and posterior valve obstruction. Also drug history should be taken particularly asking about anti-histamines and anti-cholinergics. Detailed investigations should be carried out like Ultrasound Abdomen plus KUB and prostate with pre and post void, Urodynamic studies to asses bladder function and to rule out VUR and whether bladder augmentation needed before transplant or not. Cystoscopy may be needed in few cases to diagnose bladder cancer .Treatment depends on the cause and it should be addressed before transplantation. However,in the case of BPH –prostate should be resected after transplant due to high chances of urethral stricture in anuric patients.
REFERENCES:
1-Infante B, Rossini M, Leo S, Troise D, Netti GS, Ranieri E, Gesualdo L, Castellano G, Stallone G. Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem. Int J Mol Sci. 2020 Aug 19;21(17):5954.
2- Antoniewicz AA, Zapała Ł, Bogucki A, Małecki R. The standard of urological consultation of patients qualified for renal transplant – a review. Cent European J Urol. 2015;68(3):376-82
IgA nephropathy is one of the glomerulonephritis caused by abnormal galactose-deficient (Gd)-IgA1-specific immunoglobulin G (IgG) autoantibodies which usually cause mesangial immuno-complex deposit causing glomerular hematuria and finally can cause end-stage renal disease. post-transplant IgA is associated with a risk of recurrence ranging from 20%-50% and there are some risk factors associated with increased risk of recurrence like young age, early steroid withdrawal, rapid progression to end-stage renal disease, living related kidney transplant.
back to our case, this patient gets an option from living related donor so, I will counsel them regarding paired kidney exchange or direct kidney transplant with depleting induction followed by maintenance steroids without a plan for steroid withdrawal to avoid recurrence.
A 66-year-old patient with a history of urine retention will rise an alarming flag and malignancy exclusion is needed by serological tests including tumor markers like PSA, radiological investigations like ultrasound, and some procedures may be needed like urodynamics and cystoscopy after urology referral. if there is still urine out urine analysis, urine culture and urine microscopy including RBCs in urine will be beneficial but as per history, the patient is anuric.
References
1. Moroni G, Belingheri M, Frontini G, Tamborini F and Messa P. Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation. Front. Immunol. 2019.10:1332.
2. Antoniewicz AA, Zapała Ł, Bogucki A, Małecki R. The standard of urological consultation of patients qualified for renal transplant – a review. Cent European J Urol. 2015;68(3):376-82.
2. A 66-year-old CKD 5 secondary to IgA nephropathy received a suitable kidney offer from his brother. He gave a history of retention of urine 6 months before commencing dialysis. He became anuretic when he started dialysis.
We have three concerns with this recipient
1- Recurrence of Ig A post-transplantation
The recurrence rate of IgA nephropathy is 10 -30% post-transplant. And the risk factors for recurrence include male recipient, young age at transplant, living related donor, zero mismatches with the living donor, HLA (B35, DR4, B8, DR3), rapidly progressive to ESRD, high serum IgA, and steroid withdrawal after transplant.
2- Donor
Living donors may have a risk of IgA occurrence and both recipient and donor should be counselled about this risk and may need a genetic study
There may be a place for paired kidney exchange to avoid living donor.
3- H/O urine retention
So, the recipient needs tough urological evaluation and should include a urologist in pre-transplant evaluation. The urologist can conduct urology examinations including PR for Prostate
The recipient may have obstruction (prostate, bladder cancer, urethral stricture), bladder dysfunction (due to neurological cause or medication).
S. PSA. Urine culture if can get urine or do bladder wash.
U/S abdomine and pelvis. May be CT abdomine and pelvis. Cystourethrogram with or without urodynamics.
If the recipient has obstruction, it should be treated before trasplant
This patient is 66 years old with history of both urine retention and IGA nephropathy.
IgA nephritis, may recur in approximately one third of patients, more frequently in
younger patients and in those with a rapid progression of the original disease(crescent)
Other risk factors for recurrence:
Recipients of zero-HLA mismatched live-related donor kidney.
Steroid-avoidance or early steroid-withdrawal immunosuppressive regimens.
Male gender.
Degree of proteinuria.
HLA-B35/DR4.
and higher levels of circulating Gd-IgA1 and IgA-IgG immune complexes.
Anuria with acute renal failure can occurs in patient with frank hematuria and urinary
tract obstruction .(2)
Others cause of anuria in elderly patient should be sought, including BPH ,bladder
cancer, urethral stricture ,neurogenic bladders ,drugs ,through history review and
appropriate investigation .USS ,CTU ,Urodynamic ,before transplant.
1- Barbara Infante, Michele Rossini, Serena Leo, Dario Troise, Giuseppe Stefano
Netti, Elena Ranieri et al Recurrent Glomerulonephritis after Renal Transplantation: The
Clinical Problem. Int J Mol Sci. 2020 Sep: 21(17).
2-ManuelPraga1VictorGutierrez-Mille et al. Acute worsening of renal function during
episodes of macroscopic hematuria in IgA nephropathy. Kidney International
Volume 28, Issue 1, July 1985, Pages 69-74
the recipient has a past history of IgA which can be recurrent and this will not exclude him from transplantation, the recurrence rate is 7 to 10% 10 years postrenal transplant and the recipient should be followed for proteinuria.
he had a past medical history of urine retention, a more detailed history of urine retention
urological consultation is needed, we need to evaluate the prostate and the role of any malignancy
references
_ the index case has 2 additional risks:
1_ the risk of recurrent IgA nephropathy which increases with younger age of onset, rapid progression of the disease to ESKD, presence of crescents in native kidney biopsy and in living donor with no mismatch.
_ however, the risk of recurrent IgA nephropathy does not preclude him from kidney tranplantation.
_ frequent monitoring of the protinuria post transplant is essential for early detection and treatment of recurrence
2_ the complaint of urine retention prior to transplantation must be evaluated by :
_ urological consultation , VCUG, cystoscopy and urodynic studies.
_ old age makes it essential to exclude prostatic cancer by PSA and transrectal US to evaluate the prostate .
Prostatic cancer must be treated prior to transplantation while benign prostatic hyperplasia better to be postponed after transplantation as risk of urethral stricture due to absent urine in anuric patients.
This patient has two point in history
1- History of IgA GN as underlying cause.
2- History of urine retention.
Regarding the history of IgA GN as underlying cause .
IgA nephropathy is most common cause of primary GN worldwide. Recurrence is common and increases with time. Recurrence rates are about 30%. IgA recurrence in early stages is histological which is difficult to diagnose unless biopsy is performed.
Risk factors for IgA GN recurrence are
1. younger age at transplantation.
2. Rapid progression of the native IgA.
3. Severity of proteinuria.
4. HLA matching – zero mismatch kidneys have higher rates of recurrence than those with one or more HLA mismatches.
5. ABOi- ABO-incompatible transplants have been found to have lower rates of recurrence.
Recurrence rate is not higher in living kidney transplantation.
Specific drug use has no impact on graft loss due to recurrence, although studies report protection effect of continuation of corticosteroids and antithymocyte globulin. Graft loss usually occur after three years of transplantation.
Treatment of recurrent:
There is no consensus about treatment. The addition of corticosteroid maintenance in corticosteroid free regimen although unproven but reasonable. A change to mycophenolate mofetil (MMF) or the use of fish oil, antiplatelet agents, and tonsillectomy cannot be recommended. General measures including tight blood pressure control, renin-angiotensin system (RAS) blockade, and avoidance of nephrotoxins.
Regarding the history of urine retention:
In this patient the following causes of urine retention should be searched and treated: BPH, Prostatic cancer, urethral stricture and bladder dysfunction.
As part of multidisciplinary team management this patient need urological consultation. In order to diagnose, treat, and optimize any preexisting urological disease.
1) Benign prostate hyperplasia (BPH):
Need assessment by (DRE, urine culture) and urodynamic study.
Medical treatment involves (alpha-blocker alone or in combination with 5-alpha reductase inhibitor) if the gland is over 40 mL .
bladder decompensation and elevation of residual volume, are indication for bladder emptying via clean intermittent self-catheterization CIC. Surgical treatment should be postponed in oliguric/anuric patients due to the high risk of bladder neck and urethral stricture as a result of “dry urethra syndrome”. The surgical intervention can be safely carried out even in the post-transplant.
In individuals, in whom it cannot be delayed, transurethral resection of prostate (TURP) can be performed only when combined with cystostomy.
2) Urethral stricture:
May be idiopathic, traumatic, infectious or iatrogenic . Urethrocystoscopy is recommended. Surgical intervention involves instrumental dilatation, direct visual urethrotomy or open urethroplasty .
3) Bladder dysfunctionvoiding:
Only if indicated invasive work up is needed as cystouretrography,
urodyanmic study, cystoscopy, ureteropyelography.
These patients requires a close follow-up after the surgery as the existence of bladder dysfunction adversely affects renal graft survival
and function. Abnormal bladders (patients with primary
vesicoureteric reflux or renal dysplasia, posterior
urethral valves, neurogenic bladders, vesico-ureteric
tuberculosis, bladder exstrophy and prune belly
syndrome) must be assessed urodynamically before
kidney transplant, and after the procedure adequacy
of urinary drainage must be re-assessed frequently.
4) Prostate cancer:
As this patient is above 50y he needs screening for prostate cancer
By (DRE, PSA) and if these are abnormal a biopsy under transrectal ultrasound is needed.
reffrences
1. Moroni G, Belingheri M, Frontini G, Tamborini F and Messa P. Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation. Front. Immunol. 2019.10:1332.
2. Antoniewicz AA, Zapała Ł, Bogucki A, Małecki R. The standard of urological consultation of patients qualified for renal transplant – a review. Cent European J Urol. 2015;68(3):376-82.
Precautions should be taken to minimize risk of IGA nephropathy recurrence
also should be investigated by transplant surgical team for the causes of retention
Any special consideration regarding this past medical history?
1. His original kidney disease(IgA).
2. Urological problem (urine retention and anuria in an elderly patient)
· With regard to his primary kidney disease:
IgA has a high recurrence rate post-transplant (15-40%). It can cause deterioration of the graft function and manifests clinically after 3 years. The risks of graft loss due to recurrent disease is approximately 7 to 10 % at 10 years.
Risk factors for disease recurrence are younger age, male gender, living related donor, Zero HLA mismatch living donor, rapidly progressive course of renal failure, steroid avoidance or early withdrawal, non-use of induction, crescentic IgAN in native kidneys.
Risk factors in our index case is the male gender and the living related donor offer. However, there is no basis for avoiding a living-related-donor due to the reported equivalence of graft survival independent of IgAN recurrence.
There is no known preventive therapy for IgAN recurrence. Generally, all patients with recurrent IgAN are treated with ACEIs or ARBs, which may delay progression of recurrent disease in allografts.
Tight BP control is still the key to control proteinuria with a target Bp of 130/80 for proteinuria <1g/day and <125/75 for proteinuria >1g/d.
In some selected cases with biopsy proven recurrence with crescents, and progressively increasing creatinine, and nephrotic range proteinuria, some advocate using high dose of steroids or cyclophosphamide to replace MMF for 3 months.
Therefore, the patient should be counseled about the risk of disease recurrence, particularly with the first-degree relative off. In the presence of high HLA mismatches, consider the possibility kidney Paired exchange to minimize the risk of IgA disease recurrence.
· With regard to the urine retention and anuria:
The patient requires careful evaluation by the urology as part of the multidiscipline team .
Possible causes of retention include:
Bladder outlet obstruction: BPH, Cancer prostate, urethral stricture.
Neurogenic bladder
Drugs causing urine retention like anticholinergics
Investigations include:
Checking PSA
Ultrasound KUB and trans-rectal US to evaluate the prostate
Urodynamic studies
Cystoscopy
The cause will determine the treatment plan aiming to have a sterile lower urinary tract.
References:
1. Moroni G, Belingheri M, Frontini G, Tamborini F and Messa P. Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation. Front. Immunol. 2019.10:1332.
2. Antoniewicz AA, Zapała Ł, Bogucki A, Małecki R. The standard of urological consultation of patients qualified for renal transplant – a review. Cent European J Urol. 2015;68(3):376-82.
Regardless of the basic aetiology of his kidney disease as IGAN, he should be investigated for causes that might lead again to urine retention post-transplant, such as urethral stricture, prostatic disease and others.
moreover, he should be counselled regarding the possibility of recurrence of IGAN post-transplant.
Regarding history:
Timing of development of IgA nephropathy, family history to exclude genetic susceptibility, the duration of progression of IgA to ESRD rapid or slow, response to treatment and adherence to medications.
Genetic screening for his donor brother, with exclusion of microhematuria is essential.
Counselling the patient for the high probability of recurrence.
The retention of urine episode should be investigated thoroughly, by laboratory investigation (PSA as the age is above 60 years) imaging studies as ascending cystogram, KUB, or further urodynamics if needed to exclude outlet obstruction , BPH , urothelial malignancies according to urology team recommendations.
Triple immunosuppressive regimen post transplantation is wise for such patients and this should be also discussed by the patient in details.
1) Urodynamic study is indicated to evaluate bladder dysfunction.
2) counsel donor ( Brother ) for extensive HLA assessment before transplantation.
3)Counsel recipient possibility of recurrent of IG A nephropathy after kidney transplantation. As recurrent of primary disease is common. There may be recurrent Ig A deposition in the renal allograft which lead to hematuria , proteinuria and progressive kidney dysfunction.
Possible risk factors for recurrence include the following:
1) Use of living-related-donor kidney
2) Specific human leukocyte antigen (HLA) alleles in recipient including HLA-B35, HLA-DR4, HLA-B8, HLA-DR3
3) Good HLA match between donor and recipient
4) Glucocorticoid withdrawal
5) High serum IgA concentration
6)Elevated galactose-deficient (Gd)-IgA1-specific immunoglobulin G (IgG) autoantibodies
7)Rare genetic variants in complement factor H-related protein 5 (CFHR5).
REFERENCES
Any special consideration regarding this past medical history?
66 y old male, ESRD on dialysis, primary renal disease is IgA Nephropathy, developed urine retention 6 months earlier then became anuric after starting dialysis. For renal transplantation from his brother.
IgA nephropathy:
The risk of recurrence of IgA nephropathy is 40-60% and should be explained to the patient beforehand.
Is it primary IgA-N or secondary IgA-N?
His brother is the potential donor:
The chances of MM could be 000 (1/3), or 111 (1/3) or 222 (1/3).
>60% chance of having a low immunological risk MM.
In case of familial IgA-N should be properly investigated with genetic inheritance of certain HLA types (B35 & DR4) which may lead to subclinical deposits from the donor to the recipient.
66Y-Male- Urine retention:
obstructive uropathy should be ruled out:
BPH, prostatic cancer, urethral stricture, bladder dysfunction, high UB pressure retention, small volume urinary bladder. PSA level is t be checked.
He needs USS-KUB or CT-KUB, further studies to rule out malignancy. He may need flexible cystoscopy or TURP. Management will be decided accordingly.
He needs urodynamic studies as part of routine pre-transplant assessment.
* By history ; This 66years old male patient with CKD V secondary to IgA nephropathy with a history of urinary retention and became anuric.
Regarding IgA Nephropathy ; could be either primary with high incidence of recurrence ,or secondary to viral infection as HIV, Hepatitis
(Risk factors for recurrence : younger age , no induction, , early steroid withdrawal, Good HLA match between donor and recipient , high serum IgA level, living-related-donor kidney , severity of proteinuria)
*Recurrence rate of IgA post-transplantation up to 23 % at 15 years.
* Urology consultation is important to investigate cause of urine retention with diagnostic radiological imaging as Pelvi-abdominal us with post-voiding ,urodynamic studies and cystoscopy, patient may in need for possible TURP. Because it could be benign or malignant lesion due to his old age.
References:
Uffing A, Saez M, Jouve T, et al. : Recurrence of IgA nephropathy after kidney transplantation in adults. CJASN , 2021,16 (8):1247-1255.
As he has history of retention of urine 6 months before initiation of dialysis and now he is an-uric, he need complete evaluation of his urinary bladder and lower urinary tract by urologist.
Ultrasound of KUB, Serume PSA level, and urodyanamic study should be done for him prior to transplantation under antibiotic cover.
he should be counselled about recurrence of IgA nephropathy.
in the multi-center post transplant glomerular disease cohort study, the cumulative incidence of recurrence was 19 %at 10 years and 23 % at 15 years, Among the patients with recurrent IgA , the median time to recurrence was 3.4 years
The recipient has a past history of IgA nephropathy. Recurrence rate of this condition is 30%. IgA nephropathy can recur after kidney transplant and can even lead to graft loss. The patient has a 3.7 fold higher risk of graft loss.
The patient is 66 years old. Increasing age of recipient increases the risk of IgA nephropathy. Female patients are more at risk in the first year of transplantation, while after the first year, male patients have slightly higher risk of recurrence.
Biomarkers such as Gd – IgA1 can predict recurrence of IgAN.However this cannot be taken as an absolute standard since there are many studies that reveal this cannot be relied upon.
High dose prednisone followed by stable low dose could have a positive impact on any predicted recurrence.
References
:
– Risk of IgA recurrence is 40-50% with risk of graft loss 5-15% 10 years after renal transplantation.
They include :Young age at transplantation, rapid deterioration of IgA N , severity of proteinuria. Higher rate of recurrence of IgA N occurs in cases of living related donor compared with deceased donor. 1 or more HLA mismatches was found to reduce rate of recurrence compared with zero mismatch kidneys. IgA deposits in the donor kidney increase rate of recurrence.
-Patient should be evaluated by urologist for BPH, ruling out possibility of malignancy and PSA level screening .
– prostate resection can be delayed after transplantation as the patient is currently anuric .,with Foley catheter or self catheterization till prostatic resection.
.
Danovitch,G Handbook of hkdney transplantation
The rate of graft failure in patients with recurrence was 2.8-fold higher than in patients without recurrence.
(IgAN) after kidney transplantation occurs in about 30% of patients.
Regarding retention, an elderly patient with recurrent retention requires urological evaluation including history and PE,DRE, uroflowmetry, psa US with pre and post void residual.
Then, treatment to be done accordingly by medical or surgical intervention to prevent bladder outlet obstruction and susequent kidney failure.
Jäger, C., Stampf, S., Molyneux, K. et al. Recurrence of IgA nephropathy after kidney transplantation: experience from the Swiss transplant cohort study. BMC Nephrol 23, 178 (2022). https://doi.org/10.1186/s12882-022-02802-x
In patients who received a kidney transplantation for kidney failure due to IgA nephropathy, IgA deposits can recur in the transplanted kidney. The clinical course of recurrent IgA nephropathy is variable because it can be diagnosed in patients on a protocol biopsy who are asymptomatic, in patients with mild hematuria or proteinuria, or in patients with rapidly deteriorating kidney function. As a result, reported rates of recurrence vary significantly between 9% and 61%, mainly due to diverse biopsy protocols and differences in follow-up.
Recent studies have shown that recurrence of IgA nephropathy usually manifests a couple of years after transplantation, and longer follow-up studies showed lower survival rates after 5–10 years . Reported graft loss due to recurrent IgA nephropathy varies from 2% to 14% in studies with medium follow-up .
A number of risk factors for IgA nephropathy recurrence have been described, including 1- younger age at transplant
2- transplant without an induction agent,
3- higher HLA-mismatch,
4- early steroid withdrawal immuno-suppressive regimens .
references:
recurrence of IgA nephropathy after kidney transplantation
Any special consideration regarding this past medical history?
Regarding IG A nephropathy
There is risk of recurrence in patients with IgAN
Histologic recurrence, with or without evidence of clinical disease, is common
The true risk of significant graft dysfunction and/or graft loss from recurrent disease is unclear
Possible risk factors for recurrence include the following:
●Use of living-related-donor kidney
●Specific human leukocyte antigen (HLA) alleles in recipient including HLA-B35, HLA-DR4, HLA-B8, HLA-DR3
●Good HLA match between donor and recipient
●High serum IgA concentration
Regarding history of retentionage 66 need to invesitgat it carefully
evaluate prostate for BPH or malegnancy(US , CT , PSA)
bladder contractility function , size / neurogenic bladder
In this patient age, i would first consider his LUTS and assess it using pelvic abdominal u/s , PSA, and urine analysis with culture to exclude lower UT causes.
Being a previous patient of IgA, there is still consideration of recurrence of original disease. Rates as per some studies was 21-58%. (1)
I would like to assess for proteinuria , hematuria before dialysis, and if also he had done biopsy of allograft to diagnose recurrent IgA nephroapthy or no.
references:
1- Odum J, Peh CA, Clarkson AR, Bannister KM, Seymour AE, Gillis D, Thomas AC, Mathew TH, Woodroffe AJ. Recurrent mesangial IgA nephritis following renal transplantation. Nephrol Dial Transplant. 1994;9(3):309-12. PMID: 8052439.
We have 2 considerations in the is case
I) the original disease: as it might recur in the graft and patient should be aware about that up to 50% chance to recur; however, it has low risk to develop ESRD due to recurrence
II) the urinary retention
Was it surgical, or medical cause, so we need to take thorough history about the associated symptoms with retention (pain, hematuria, hesitancy, urgency). So, we need to involve the urologist in this consideration.
If any disease can be corrected so need to put a plan to treat it to avoid future retention in the graft. If any suspected prostatic cancer, we need to investigate it carefully to not miss active malignancy
In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in kidney transplant. There is a cumulative risk of IgA nephropathy recurrence that increased after transplant and is associated with a 3.7-fold greater risk of graft loss. Usually IgA nephropathy occurs a couple of years after transplantation. Lower survival rates after 5–10 years have been shown by longer follow up studies. Medium follow up studies showed that graft loss due to recurrent IgA nephropathy varies from 2% to 14. On the other hand long term follow up studies have shown an increased graft loss up to 29% in patients with symptomatic recurrent disease
There are several risk factors for IgA nephropathy recurrence, including younger age at transplant, transplant without an induction agent, higher HLA-mismatch, and early steroid withdrawal immunosuppressive regimens.
The incidence of IgA nephropathy recurrence increased gradually after transplant with a cumulative incidence of 19% at 10 years, and 23% at 15 years after kidney transplantation.
Considering the patient’s age and clinical presentation he should require a complete evaluation of urinary system for BPH, prostate cancer, stone, UTI, neurogenic bladder.
Patient on dialysis may have reduced capacity (in particular if they are oliguric or anuric) of urinary bladder therefore he may require investigation to assess volume of the urinary bladder and detrusor activity. He may require urodynamic study or even cystoscopy.
Radiology imaging used to assess the urinary system include ultrasonography, CT scan or MRI). Considering his age and gender he needs PSA.
If patient has BPH and still passing urine the prostate resection can be done after transplantation and therefore he should have urinary catheter until prostate resection.
In case of bladder dysfunction (secondary to chronic infection or neurogenic bladder) this patient can be often managed with self-catheterization.
Recurrence of IgA Nephropathy after Kidney Transplantation in AdultsAudrey Uffing, Maria José Pérez-Saéz, Thomas Jouve, Mathilde Bugnazet, Paolo Malvezzi, Saif A. Muhsin, Marie-Camille Lafargue, Roman Reindl-Schwaighofer, Alina Morlock, Rainer Oberbauer, Anna Buxeda, Carla Burballa, Julio Pascual, Seraina von Moos, Harald Seeger, Gaetano La Manna, Giorgia Comai, Claudia Bini, Luis Sanchez Russo, Samira Farouk, Pitchaphon Nissaisorakarn, Het Patel, Nikhil Agrawal, Gianna Mastroianni-Kirsztajn, Juliana Mansur, Hélio Tedesco-Silva, Carlucci Gualberto Ventura, Fabiana Agena, Elias David-Neto, Enver Akalin, Omar Alani, Marilda Mazzali, Roberto Ceratti Manfro, Andrea Carla Bauer, Aileen X. Wang, Xingxing S. Cheng, Jesse D. Schold, Stefan P. Berger, Paolo Cravedi and Leonardo V. Riella
CJASN August 2021, 16 (8) 1247-1255; DOI: https://doi.org/10.2215/CJN.00910121
Antoniewicz AA, Zapała Ł, Bogucki A, Małecki R. The standard of urological consultation of patients qualified for renal transplant – a review. Cent European J Urol. 2015;68:376–382.
There are three considerations for this elderly transplant candidate,
Age the age of the patient is greater 50years. With all the risk associated elderly transplants. Although it was mot awarded for how long he was on dialysis
With IgA nephropathy and a terminal anuria we should be worried about recurrent of the disease in the transplant kidney.
The history of Lower urinary symptoms would bean indication to investigate for obstructive uropathy. This will be necessary to assess by urologist and sorted before transplant. Including ultrasound , micturation studies and screening for prostrate cancer
Being a case of IgA nephropathy, there is a risk of disease recurrence ( 30%), but it rarely manifests before 3 years. There is no particular recurrence predictor; known risk factors are young age at renal transplant, rapid progression of the original disease and higher levels of circulating galactose-deficient IgA1 and IgA-IgG immune complexes, and early steroid withdrawal post-transplant.
Regarding urinary retention, a thorough evaluation should be done to identify and treat the cause like prostatic hyperplasia or BPH, obstructing stone, bladder outlet obstruction, pelvic organ prolapse (rectocele), constipation, neurogenic bladder, and drug-induced ( anticholinergic drugs).
References:
recurrence rate of histologic which is common,but rate of graft loss is very how
IgA nephropathy could be familiar in some cases and so the brother as donor should be evaluated completely.
Risk of recurrence would be increased in the following conditions:
Stopping prednisolone.
Also, due to history of urinary retention specialy with his age, complete evaluation of urinary system for BPH, stone, UTI, neurogenic bladder.
There are two things about this patient.
First of all, Ig A nephropathy has a recurrence rate of histologic which is common (40- 60%), but rate of graft loss is very how (about 10% of patients). IgA nephropathy could be familiar in some cases and so the brother as donor should be evaluated completely. Risk of recurrence would be increased in the following conditions:
(1) Stopping prednisolone (2) Class HLA match (especially in the related donor) (3) high serum IgA (4) Specific HLA Alleles (5) No induction C.
Considering PKD could be helpful.
Secondly, due to history of urinary retention, complete evaluation of urinary system for BPH, stone, UTI, neurogenic bladder is important. This could be done by imaging (ultrasonography, CT scan or MRI), lab tests (such as PSA), or urodynamic studies or even cystoscopy
#Any special consideration regarding this past medical history?
*To manage this patient two special consideration we should put in importance, IgA nephropathy and the history of urine retention.
* Cumulative incidence of recurrent IgA nephropathy was 19% at 10 years and 23% at 15 years after kidney transplantation.
In multivariable analysis to risk factors, a pre-emptive transplant and presence of DSA at time of transplantation were associated with recurrence of IgA deposits.
Recurrent IgA nephropathy was mostly found on clinically indicated biopsy (95%), and was independently associated with a 3.7-fold higher risk of graft loss.
Clinical presentation at time of recurrence was of importance for graft survival because patients with proteinuria had worse outcomes compared with patients without.
Studies had found an association between living (related) donation and IgA nephropathy recurrence
Both IgA nephropathy recurrence and dnDSA could reflect a primary lack of sufficient immunosuppression(1).
* Basic evaluation of the urinary tract is performed in all patients during qualification for kidney transplantation to exclude urinary tract infection, cancers, urinary obstruction and to assess the need for native kidney nephrectomy. Detailed medical history, physical examination, urine test and culture, blood PSA level in male recipients and ultrasound of the urinary tract are sufficient in most cases. Anatomical or functional abnormalities, such as urinary retention, vesicoureteral reflux, decreased urinary bladder capacity, are indications for more complex urological evaluation. These problems may result from congenital urinary tract disorders and affect up to 25% of children with end-stage kidney disease. However, detailed urological evaluation should be considered in all patients with unknown cause of renal failure.
*Some questions should be answered during urological evaluation:
1. Is there any potentially curable form of obstruction in urine outflow?
Anatomic obstruction, i.e.: urethral stricture, posterior urethral valve or bladder neck fibrosis, requires surgical treatment before kidney transplantation. In case of benign prostatic hyperplasia in patients with oliguria, surgery, if necessary, may be postponed after kidney transplantation.
2. Is the recipient’s bladder function sufficient to ensure proper excretion of urine?
This assessment must cover both the size and capacity of the urinary bladder and detrusor activity. Reduced capacity of the urinary bladder is common problem in patients on dialysis with long lasting oliguria, however bladder dysfunction in such cases is temporary and usually rehabilitation is fast and uneventful after transplantation. In rare cases of permanently impaired bladder capacity surgical augmentation should be considered.
ditions exist: passive or active vesicoureteral reflux, urolithiasis, hydronephrosis, urinary fistula?
In such cases, unilateral or bilateral nephrectomy is usually necessary before transplantation. Patients with significantly enlarged kidney may also need pretransplant nephrectomy.
Proper diagnosis and correction of urological disorders during evaluation of a potential kidney recipient prevents complications after transplantation and improves kidney graft survival(2).
References
1. Marinaki S, Lionaki S, Boletis JN: Glomerular disease recurrence in the renal allograft: A hurdle but not a barrier for successful kidney transplantation. Transplant Proc 45: 3–9, 2013 [PubMed] [Google Scholar]
2.Antoniewicz AA, Zapała Ł, Bogucki A, Małecki R. The standard of urological consultation of patients qualified for renal transplant – a review. Cent European J Urol. 2015;68:376–382. [PMC free article] [PubMed] [Google Scholar]
☆Concerning the past medical history of this 66-year-old CKD 5 secondary to IgA nephropathy who received a suitable kidney offer from his brother and gave a history of retention of urine 6 months before commencing dialysis.
▪︎ First we must consider the risk of recurrence of IgA nephropathy post transplantation which include: time on dialysis, age at transplantation ( younger age has more risk), pre-emptive transplant, presence of preformed DSA (so we must investigate for it’s presence), and time of kidney failure, transplant without an induction agent, higher HLA-mismatch, and early steroid withdrawal immunosuppressive regimens [1].
▪︎Concerning his urological symptoms.
– We will consult a urologist – A thorough history, physical examination, and selected diagnostic testing should be done to determine the cause of urinary retention.
– We should investigate him for the cause of urine retention which include: benign prostatic hyperplasia, prostatitis, cystitis, urethritis, prostatic carcinoma and urogenic bladder prior to transplantation [2].
_________________________
Ref:
[1] Audrey Uffing et al. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults.
Clin J Am Soc Nephrol. 2021 Aug.
[2] BRIAN A. SELIUS et al. Urinary Retention in Adults: Diagnosis and Initial Management.
Am Fam Physician. 2008;77(5):643-6500
Looking at your response, I must comment on the timing of TURP in an aneuric or oliguric patient.
I would bring your attention to Dr. Abhijit Patil’s comment and I would paraphrase that as follows:
If TURP is performed before transplant in such patients, the prostatic fossa heals with fibrosis and results in the narrowing of the urinary tract. The urine stream keeps the channel open until the process of epitheliaisation of the operated area is complete.
Ajay
66 years old male patient : After proper history regarding the medical , family , dialysis , previous pre-transplant investigations and renal biopsy revised.
Special considerations are to be taken regarding the previous history :
-IgA nephropathy has a genetic background so further analysis of the donor should be done.
-IgA nephropathy is a recurrent post RTx disease in 20-60% but although histological recurrence occurs , graft loss is thankfully uncommon.
Recurrence is increased in cases of living related donor, rapidly progressive disease , no induction with ATG and steroids withdrawal.
regarding the Urological issue :
-Full history -examination – mUrosurgical consultation should be done -PAUS with assessment of post voiding volume if any
-Ascending cystourethrography can be done
-PSA levels
-BPH – neurogenic bladder should be excluded (Diabetic ?)
>>regarding IgA nephropathy as the primary glomerular disorder :
(Handbook Of Kidney Transplantation 6th)
1- increased rate of recurrence in patients with a living related donor compared with a deceased donor ; however, this finding is inconsistent and should not preclude consideration of living donor transplantation for patients with IgAN.
2- those with 1 or more HLA mismatches have a reduced rate of recurrence compared with those with zero mismatch kidneys.
3- presence of IgA deposits in the donor kidney.
( Wyld, Melanie L. MBBS , transplantation journal , September 2016 )
>>regarding the urine retention 6 months before commencing dialysis :
(Handbook Of Kidney Transplantation 6th)
There are two important issues in the patient’s medical history:
Recurrence of IgA nephropathy in the graft:
The incidence of IgA nephropathy recurrence is 19% at 10 years and 23% at 15 years after kidney transplantation.
Risk factors for recurrence:
Male gender
Young age
rapidly progressive original disease before transplant
pre-emptive transplant
presence of DSA before transplant
References:
Evaluation of lower tract of the elderly recipient:
This scenario discuss to issues
The first one is the recurrence of IgAN post transplantation.
Recurrent IgA nephropathy is common,but occurs late post-transplant with cumulative incidence of disease recurrence at 15 year 15%.
Following disease recurrence, up to 40% of patients with recurrent IgA nephropathy have been reported to lose their allografts, predominantly from disease recurrence (up to 60%) .
Risk factors for disease recurrence include :
younger age,
recipients of zero-HLA-mismatched live-related donor kidneys,
steroid-avoidance or early steroid- withdrawal immunosuppressive regimens,
the non-use of induction therapy (whereas anti-thymocyte globulin [ATG] may be associated with a lower risk of recurrence),
HLA allelic subtypes,
crescentic (and rapidly progressive) IgA nephropathy in the native kidneys
and shorter total ischemic time.
There are several molecules, including galactose-deficient IgA1 (Gd-IgA1), IgG anti-Gd-IgA1 antibodies, glycan-specific IgG antibodies, and soluble CD89 (an Fc receptor for IgA) that may be implicated in the pathogenesis of IgA nephropathy, the presence of which may portend a greater risk of disease progression and possibly disease recurrence post- transplant .There are several other non-specific serum and urine biomarkers that may predict the risk of disease recurrence after kidney transplantation, but the prognostic (and predictive) performance of many of these biomarkers have not been truly established or validated in independent population cohorts .
The second issue is the urine retention 6 months before renal transplantation in an old age candidate.
Potential causes of obtrusive uropathy include:
BPH
Prostatic ca.
Bladder neck mass
Urethral stricture
Neurogenic bladder
So we need full work up to determine the cause like abdominal and pelvic ultrasound
CT scan
Urodynamic study
Cystoscope
Retrograde urethrogram.
Reference:
Recurrent and de novo Glomerulonephritis After Kidney Transplantation
Wai H. Lim1,2*, Meena Shingde3 and Germaine Wong4,5,6
Any special consideration regarding this past medical history?
The index patient is a 66-year-old male with CKD on haemodialysis. His primary disease is IgA nephropathy. He had history of urinary retention and anuric.
1st issue – urinary retention:
Transplant recipient should be evaluated lower urinary tract should be sterile, free of any bladder outlet obstruction and malignancy. Patient had history of urinary retention and now anuric:
Further evaluation needed:
a) Detailed history
b) Clinical examination
c) Urine examination
d) Ultrasound KUB
e) Serum PSA
f) voiding cystourethrogram (VCUG)
g) Urethro-cystoscopy
Treat the underlying cause:
a) BPH- if patients are still passing sufficient volumes of urine, the prostate should be resected preoperatively. Otherwise, the operation should be postponed until after the transplantation has been successfully performed. These patients may require an indwelling bladder catheter or be prepared to self-catheterize until the prostate has been resected.
b) prostatic cancer- need evaluation and treatment followed by waiting period as per the stage (Gleason <7: No wait, Gleason 7: 2 years, Gleason 8-10: 5 years)
c) Bladder dysfunction- bladder dysfunction secondary to neurogenic bladder and those who have chronic infection can often be managed without urinary diversion or bladder augmentation procedures. Self-catheterization may be an acceptable option for some patients, infection being a major complication. Graft implantation into the native bladder is always preferred. Diverted urinary tracts should be undiverted where possible to make the lower urinary tract functional before transplantation.
2nd issue- Primary disease: IgAN
Evidence of histologic recurrence of immunoglobulin A (IgA) nephropathy is common, although graft loss due to recurrent IgA nephropathy is uncommon and has been reported in about 10% of patients. Recurrent IgA nephropathy in a prior transplant is generally not a contraindication for repeat transplantation, and re-recurrence is not inevitable. IgA nephropathy may be familial in some cases, and donors should be carefully screened.
The risk factors for recurrence of IgA nephropathy post-transplant include:
a) young age at renal transplantation
b) Male gender
c) Rapidly progressive course of renal failure
d) Zero HLA mismatch living donor, a living related donor
e) High serum IgA concentration (>222.5mg/dl)
f) Early steroid withdrawal post-transplant
g) Increased Galactose-deficient (Gd)-IgA1-specific IgG antibodies
h) Specific HLA alleles in recipient: HLA-B35, HLA-DR4, HLA-B8, HLA-DR3
So, we need to seek urologist opinion regarding his urinary retention and plan for treatment for his urinary retention. With regards with IgAN , we shall take extra precautions to prevent recurrence.
References:
1) Antoniewicz AA, Zapała Ł, Bogucki A, Małecki R. The standard of urological consultation of patients qualified for renal transplant – a review. Cent European J Urol. 2015;68(3):376-82. doi: 10.5173/ceju.2015.551. Epub 2015 Oct 15. PMID: 26568885; PMCID: PMC4643699.
2) Ciszek M. Urological evaluation prior to renal transplantation. Cent European J Urol. 2015;68(3):383. doi: 10.5173/ceju.2015.e107. Epub 2015 Oct 15. PMID: 26568886; PMCID: PMC4643718.
3) Sackett DD, Singh P, Lallas CD. Urological involvement in renal transplantation. Int J Urol. 2011 Mar;18(3):185-93. doi: 10.1111/j.1442-2042.2010.02707.x. Epub 2011 Feb 8. PMID: 21299639.
4) Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, Kumar D, Oberbauer R, Pascual J, Pilmore HL, Rodrigue JR, Segev DL, Sheerin NS, Tinckam KJ, Wong G, Knoll GA. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020 Apr;104(4S1 Suppl 1):S11-S103. doi: 10.1097/TP.0000000000003136. PMID: 32301874.
5) Uffing A, Hullekes F, Riella LV, Hogan JJ. Recurrent Glomerular Disease after Kidney Transplantation: Diagnostic and Management Dilemmas. Clin J Am Soc Nephrol. 2021 Nov;16(11):1730-1742. doi: 10.2215/CJN.00280121. Epub 2021 Oct 22. PMID: 34686531; PMCID: PMC8729409.
6) Infante B, Rossini M, Di Lorenzo A, Coviello N, Giuseppe C, Gesualdo L, Giuseppe G, Stallone G. Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review of the incidence, risk factors, pathophysiology and management of immunosuppressive therapy. Clin Kidney J. 2020 Jun 15;13(5):758-767. doi: 10.1093/ckj/sfaa060. PMID: 33123355; PMCID: PMC7577761.
First regarding IgA nephropathy:
Seconds urological evaluation is mandatory regarding the urine retension( and the duration of anuria) managment prior transplant to prevent any risk facter/ complication post transplant.
GN is an important & common cause of ESRD, & IgAN is the most common primary glomerular disease worldwide. The recurrence variable range from 9%-61% which may be asymptomatic discovered during protocol biopsy 0r presented as HT, proteinuria or rapid deterioration of graft function. Although recurrence is high but graft loss can occur in ~29% of recurrent cases. Risk factors of recurrence include ;
It was found that IgAN recurrence risk increased with live-related donor, but with non significant risk of graft loss.
So the patient should be informed about the risk of recurrence & importance of steroid based maintenance immunosuppression.
Pre-transplant comprehensive urological assessment by a urologist is mandatory to exclude unseen or symptomatic malignancy, stone, urinary tract malformation & BPH.
References:
In presence of history of urinary retention he would require urology clearance for transplant.It could be because of BPH and any underlying Ca prostate should be ruled out, obviously urologist will look into other causes of acute retention as well.
Since primary disease is IgA and donor is living related one has to always consider risk of recurrence and should be discussed with patient.
Good HLA match , short course of disease, cresentic IgA, specific HLA typing like HLA-B35, HLA-DR4, HLA-B8, HLA-DR3 etc are risk factors for recurrence however there presence should not create any hinderence.
The mentioned patient is 66 y old with:
1. history of urine retention 6 months before starting dialysis.
2. History of IgAN as a cause of his kidney disease.
Consideration regarding this patient past medical history:
Urine retention obstructive uropathy work-up have to be fulfilled for treatment of reversible and manageable causes before transplant procedure.
Possible causes of urine retention in this case are:
· Bladder outlet obstruction: BPH, Ca-Prostate, bladder neck mass, urethral stricture.
· Neurogenic bladder
· Drugs with adverse effects manifesting as urine retention( antihistamines and anticholinergics).
The patient may need the followings to identify the cause of his urine retention:
· Ultrasound scanning of the abdomen and pelvis to give a clue about the prostate.
· CT abdomen looking at KUB and ruling out compressing masses and retroperitoneal fibrosis.
· Cystoscopy and urodynamic testing may help identifying neurogenic bladder and bladder lesions.
· Retrograde urethrogram may be needed to rule out urethral stricture.
IgAN is a highly recuring disease in the post-transplant period at a range of 15% and up to 40% of IgA recurrent patients tend to lose the graft with 1.6% proportion of allograft failure secondary to recurrence.
· Risk factors for disease recurrence: younger age, zero-mismatch LRD, steroid avoidance or early withdrawal, non-use of induction, crescentic IgAN in native kidneys and shorter total ischemia time.
· No optimal treatment is known for recurrence, the practice to continue CNI, steroids and antiproteinuric.
· In crescentic and RPGN more aggressive therapy is needed (cyclophosphamide or rituximab) although not having a proven outcome. Tonsillectomy has limited potential benefit.
This 66-year male with primary IgA and urine retention have many problems: age with higher risk of cardiovascular disease (we discussed before), more risk of malignancy, IgA nephropathy risk of recurrence, and urine retention which could be difficult to treat in some cases.
Transplantation is the treatment of choice for individuals with progressive kidney failure due to IgA nephropathy (IgAN), which is caused by the deposition of IgA in the kidney parenchyma.
Recurrent IgA deposition in the allograft is common and may cause hematuria, proteinuria, or progressive kidney dysfunction. Among some patients, however, IgA deposits are observed on biopsy but do not appear to cause clinically significant disease.
IgA deposition may occur alone or be concurrent with other significant pathology, including chronic rejection [1]
In the multicenter Post-Transplant Glomerular Disease (TANGO) cohort study of 504 transplant recipients with biopsy-proven IgAN as the cause of end-stage kidney disease (ESKD) in the native kidneys, the cumulative incidence of recurrence was 19 percent at 10 years and 23 percent at 15 years [2]. Among patients with recurrent IgAN, the median time to recurrence was 3.4 years.
Possible risk factors for recurrence include the following:
●Use of living-related-donor kidney
●Specific human leukocyte antigen (HLA) alleles in recipient including HLA-B35, HLA-DR4, HLA-B8, HLA-DR3
●Good HLA match between donor and recipient
●Glucocorticoid withdrawal
●High serum IgA concentration
●Elevated galactose-deficient (Gd)-IgA1-specific immunoglobulin G (IgG) autoantibodies
●Rare genetic variants in complement factor H-related protein 5 (CFHR5)
●Recipient age: younger age at the time of transplantation was a risk factor for disease recurrence and eventual development of allograft dysfunction [3]
Donor effect — The risk of recurrence may be higher among recipients of living-related-donor kidneys, compared with deceased-donor kidneys. Therefore, the expected advantage in allograft survival with a living-related- compared with deceased-donor source could be less.
However, there is no basis for avoiding a living-related-donor source, largely due to the reported equivalence of graft survival independent of IgAN recurrence, but also given the expected deceased-donor waiting-list time and a reported decrease in patient mortality and increase in graft survival with earlier transplantation in relation to time on dialysis [4].
Conflicting data exist concerning a possible increased risk for recurrent IgAN in recipients of living, related allografts, compared with that with unrelated (living- or deceased-donor) allografts.
PREVENTION : There is no known preventive therapy for IgAN recurrence.
Among transplant recipients, there are no conclusive data that the selection of immunosuppressive therapy alters the risk of recurrence (other than glucocorticoid withdrawal)
There is some evidence that the use of mycophenolate mofetil may decrease the risk of IgAN recurrence in the short term [5]
Limited data showed that kidney transplant patients who used cyclosporine had less recurrence [6]
A retrospective analysis reported that the prevalence of recurrent IgA following transplantation was significantly reduced in patients receiving antithymocyte globulin, compared with either interleukin-2 (IL-2) induction or no induction treatment [7]
CLINICAL MANIFESTATIONS: Patients with recurrent IgA may present with:
●Isolated microscopic hematuria or
●Isolated proteinuria or
●Microscopic hematuria plus proteinuria or
●Isolated increase in serum creatinine or
●Increased creatinine with either hematuria or proteinuria
If IgAN recurs,the mean time to clinical recurrence and allograft failure was 31 and 63 months, respectively
Patients who had a rapidly progressive course to end-stage kidney disease (ESKD) in the native kidney tend to present early after transplantation with clinically significant recurrence
DIAGNOSIS: All agree that, among transplant recipients with a history of IgAN, the following are indications for a transplant biopsy:
· An elevated creatinine above baseline, and/or
· Significant proteinuria (defined as >500 mg/day) despite an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and/or
· Persistent hematuria in the setting of a negative urologic evaluation
TREATMENT
all patients with recurrent IgAN should be treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). Treatment with an ACEI or ARB may delay progression of recurrent disease in allografts [8].
There have also been case reports of fish oil having a favorable effect in recurrent IgAN, but no studies have been performed to support its routine use
In high risk patients, high-dose glucocorticoids (such as prednisone 1 mg/kg/day) may be given for two months, followed by a slow taper back to low doses commonly used to prevent rejection.
Patients who have a rapidly increasing serum creatinine despite high-dose glucocorticoids may benefit from oral or intravenous cyclophosphamide, based upon studies of patients with IgAN in the native kidney.
If cyclophosphamide is used, the current antimetabolite used to prevent rejection (usually mycophenolate mofetil or azathioprine) should be discontinued for the duration that the patient is on cyclophosphamide to mitigate the risk of severe myelosuppression.
The use of rituximab in the treatment or prevention of recurrent IgAN has not been studied.
PROGNOSIS
Historically, it was thought that, despite the risk of recurrent disease, among patients with a history of IgAN, the overall graft survival was similar to that of patients with a history of non-IgA glomerular or nonglomerular disease.
Recurrent IgAN in combination with chronic rejection has a worse prognosis, compared with recurrent IgAN alone
Markers for progression — As with all glomerulopathies, increased urinary protein excretion and increased sclerosis and fibrosis on kidney biopsy with IgAN are associated with an enhanced risk of progressive disease.
Although persistent microscopic hematuria may be an early marker of recurrent IgAN, its onset does not necessarily predict a poor outcome.
According to urine retention should be investigated and treated before proceeding for kidney transplantation
Acute urinary retention (AUR) is common in men. The incidence increases with age, occurring most frequently in men over age 60. The most common mechanisms are outflow obstruction, neurologic impairment, or an inefficient detrusor muscle. Other causes include medications, infection, and trauma.
●Outflow obstruction – Obstruction is the most common cause of AUR.
•In males, the most common cause of obstruction is benign prostatic hyperplasia (BPH). Other causes of outflow obstruction in men include constipation, prostate or bladder cancer, urethral stricture, urolithiasis, phimosis, or paraphimosis
●Neurologic impairment – AUR may develop secondary to the interruption of the sensory or motor nerve supply to the detrusor muscle.
AUR can occur with spinal cord injuries from trauma, infarct or demyelination, epidural abscess and epidural metastasis, Guillain-Barré syndrome, diabetic neuropathy, and stroke.
Patients with neurologic impairment may develop acute-on-chronic urinary retention.
●Inefficient detrusor muscle
●Medications: alpha-adrenergic agents, beta-adrenergic agents, Antidepressants, Antiarrhythmics, Anticholinergics, Antiparkinsonian agents, Hormonal agents (Progesterone, Estrogen, Testosterone), Antipsychotics, Antihistamines (selected), Antihypertensives (Hydralazine, Nifedipine), Muscle relaxants, Indomethacin, Carbamazepine, Amphetamines, Dopamine, Vincristine, Morphine sulfate and other opioids, Anesthetic agents.
●Infection: acute prostatitis, urethritis, Genital herpes, varicella zoster and vulvovaginitis.
●Trauma – Patients with trauma to the pelvis, urethra, or penis may develop AUR from mechanical disruption
DIAGNOSIS: good history, clinical examination, ultrasound pelvis initially.
If the patient in acute distress, it is reasonable to proceed directly to catheterization, which is both diagnostic and therapeutic, rather than waiting to obtain a bladder ultrasound.
There is some controversy regarding the role of diagnostic studies in the evaluation of males with lower urinary tract symptoms (LUTS) who are referred to a urologist. Guidelines from the American Urological Association (AUA) advise that all testing (including uroflowmetry, postvoid residual [PVR], pressure-flow urodynamics, and cystoscopy) be considered optional [9]
Invasive diagnostic studies — More invasive studies include pressure-flow urodynamic studies, cystoscopy, and measurement of prostate volume by transrectal ultrasound.
Pressure-flow studies and urodynamics: important in the evaluation of male patients with neurologic disease and in patients who fail treatment for BOO. Urodynamics are often performed before empiric treatment, when a non-BOO etiology is suspected, or when invasive treatment is contemplated. Additionally, men under age 50 should be evaluated with urodynamic studies prior to treatment due to the high incidence of non-obstructive etiology for LUTS in this population
Urine analysis and culture if urine obtained.
PSA should not be done in acute retention, but later on after improvement.
[1] https://www.uptodate.com/contents/iga-nephropathy-recurrence-after-transplantation?search=iga%20nephropathy&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4#:~:text=Transplantation%20is%20the,including%20chronic%20rejection
[2] Uffing A, Pérez-Saéz MJ, Jouve T, et al. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Clin J Am Soc Nephrol 2021; 16:1247.
[3] https://www.uptodate.com/contents/iga-nephropathy-recurrence-after-transplantation/abstract/12
[4] https://www.uptodate.com/contents/iga-nephropathy-recurrence-after-transplantation/abstract/27
[5] https://www.uptodate.com/contents/iga-nephropathy-recurrence-after-transplantation/abstract/7
[6] https://www.uptodate.com/contents/iga-nephropathy-recurrence-after-transplantation/abstract/26#:~:text=PubMed,2011%20Dec%2013.
[7] https://www.uptodate.com/contents/iga-nephropathy-recurrence-after-transplantation/abstract/42
[8] https://www.uptodate.com/contents/iga-nephropathy-recurrence-after-transplantation?search=iga%20nephropathy&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4#H2191323510:~:text=creatinine%20remained%20stable.-,TREATMENT,ARB%20may%20delay%20progression%20of%20recurrent%20disease%20in%20allografts%20%5B47%2C48%5D.,-We%20suggest%20that
[9] https://www.uptodate.com/contents/lower-urinary-tract-symptoms-in-males?search=urinary%20retention%20in%20men&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3#H15:~:text=There%20is%20some,optional%20%5B30%5D
As patient is 66 -years-old, I will ask history regarding bladder outlet obstruction like, urgency, hesitency, dribbling in the past. I will examine his prostate by DRE. I will do USG KUB with prostate, S PSA.
As patient is Ig A nephropathy, he might got steroid and might had diabetes. I will search for features of neuropathy as he may have neurogenic bladder.
I will also take drug history to find any drug causing retention like tryhexiphenidil as he might have parkinsons disease too.