|Year : 2017 | Volume
| Issue : 2 | Page : 86-88
Renal transplant in a child with Alport syndrome
Rajendra B Nerli1, Shridhar C Ghagane2, Mahantesh V Patil3, Neeraj S Dixit2
1 Department of Urology, KLES Dr. Prabhakar Kore Hospital and MRC, KLE University's JN Medical College, KLES Kidney Foundation, Belgaum, Karnataka, India
2 Department of Urology, KLES Dr. Prabhakar Kore Hospital and MRC, KLES Kidney Foundation, Belgaum, Karnataka, India
3 Department of Nephrology, KLES Dr. Prabhakar Kore Hospital and MRC, Belgaum, Karnataka, India
|Date of Web Publication||12-Sep-2017|
Rajendra B Nerli
Department of Urology, KLES Dr. Prabhakar Kore Hospital and MRC, KLE University's JN Medical College, KLES Kidney Foundation, Nehru Nagar, Belgaum - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
Alport syndrome is a rare inheritable renal disease characterized by renal, cochlear, and ocular involvement. Patients commonly require renal replacement therapy in the second or third decade of life. Renal transplantation in pediatric patients has become a routinely successful procedure, with 1- and 5-year patient survival rates of 98%, the range takes into account the differences between living and deceased donors. These good outcomes represent the cumulative effect of improvements in pre- and post-transplant patient care, operative techniques, immunosuppression, and infection prophylaxis, diagnosis, and treatment. We report the case of a male child with Alport syndrome who underwent preemptive live renal transplant and his mother was the donor.
Keywords: Alport syndrome, hereditary nephritis, renal transplantation
|How to cite this article:|
Nerli RB, Ghagane SC, Patil MV, Dixit NS. Renal transplant in a child with Alport syndrome. Indian J Transplant 2017;11:86-8
| Introduction|| |
Alport syndrome is a hereditary nephropathy characterized by progressive renal failure, sensory neural deafness, and typical ocular abnormalities. It almost inevitably leads to end-stage renal disease (ESRD) during adolescence or early adulthood. The disease is caused by mutations in type IV collagen genes, most commonly COL4A5 situated on the X chromosome accounting for 85% of cases. Female heterozygous X-linked Alport carriers show a large inter- and intra-familial variability of the clinical course and a more favorable prognosis., Heterozygous COL4A3/COL4A4 carriers develop thin basement membrane nephropathy, which may lead to an increased risk for developing progressive chronic kidney disease.
The proportion of ESRD patients commencing renal replacement therapy (RRT) due to Alport syndrome varies considerably between countries., Most patients with Alport syndrome commence RRT in early adulthood, particularly males who typically start RRT a decade earlier than females. Mallett et al. investigated the characteristics and clinical outcomes of patients from Australia and New Zealand commencing RRT for ESRD due to Alport syndrome compared with propensity score-matched, RRT-treated, non-Alport ESRD controls. A total of 58,422 patients were studied during this period of which 296 (0.5%) patients had Alport ESRD.,,,, Patients with Alport syndrome experienced comparable dialysis and renal transplant outcomes to matched non-Alport ESRD controls. We report a case of a male child with Alport syndrome who underwent renal transplant at our center.
| Case Report|| |
A 10-year-old male child presented in 2011 to the pediatric services of the hospital with symptoms of passing high-colored urine occasionally. The child had no other symptoms including high blood pressure, edema, and oliguria. Urine examination revealed micro hematuria and proteinuria (24 h urine albumin >1.5 g/24 h). His estimated glomerular filtration rate (eGFR) was 88 ml/min/1.73 m 2. Ultrasonography imaging of the kidneys showed bilateral medical renal disease. The child was started on tablet enalapril and the parents were counseled regarding renal biopsy and need for RRT in the future. Electron microscopy examination of renal biopsy revealed a glomerulus that was moderately enlarged due to marked endothelial proliferation occluding the capillary lumina. There was diffuse foot process flattening. The basement membranes were uniformly thin measuring from 60 nm to 120 nm (an average of 85 nm). No defects with thickening of the basement membranes on basket weave pattern were seen, and a final diagnosis of Alport syndrome was made.
The child is the fifth child of a second-degree consanguineous couple. He has a 24-year-old elder sister who is married. His three other elder male siblings died in childhood, cause not known. This child was born full term, vaginal delivery, following an uncomplicated pregnancy. Early developmental milestones were normal.
In July 2015, the child presented with gross hematuria, decreased urine output, generalized edema, and vomiting. He was admitted, started on hemodialysis (creatinine 7.1 mg/dl), and a repeat renal biopsy showed rapidly progressing glomerulonephritis. The child responded positively to this conservative treatment, serum creatinine stabilized at 3.35 mg/dl, and urine output maintained at 800 ml/day. The child was prepared for live-related renal transplantation. Gradually, the renal function deteriorated, and eGFR dropped down to 15 ml/min/1.73 m 2. The mother agreed to donate one of her kidneys. The donor (mother) human leukocyte antigen type A, B, and DR showed a match at A*11, B*15, B*15, and DRB 1*12 with the recipient, indicating a 4/6 match between the patient and donor. The pretransplant legal, ethical, psychological, and other clinical formalities were completed. The mother had a normal urine protein excretion, no hematuria, and no hearing or ocular deficits. Live-related preemptive transplant was performed in early 2016. The postoperative period was uneventful. Serum creatinine dropped down to 0.5 mg%. The child and his mother were discharged from the hospital within a fortnight. The child is on regular follow-up. Posttransplant anti-glomerular basement membrane (GBM) titers are being monitored and are negative.
| Discussion|| |
Pediatric renal transplantations are generally performed in specialized centers due to the need for complex technical, metabolic, immunologic, and physiologic factors; moreover it involves a multidisciplinary team comprising transplant surgeons, anesthetists, pediatric nephrologists, and urologists who are supported by public relations and pediatric nurses.,
Hemodialysis and peritoneal dialysis are the most commonly used RRT in children with ESRD. However, hemodialysis remains challenging in younger children due to difficulties with vascular access and low circulating volumes. Peritoneal dialysis allows better growth and development and improved quality of life, moreover it is cost-effective. The 5-year patient survival after renal transplantation in children is 91.7% compared with 78.6% with hemodialysis and 80.6% with peritoneal dialysis. Due to superior outcomes after kidney transplantation, most children with ESRD are referred for transplantation, in contrast with adults where only 16% of the dialysis population is listed for transplantation.
Preemptive kidney transplantation from living donors is associated with the best outcomes in children. About one-third of pediatric living donor transplantations are performed preemptively in the USA. Parents are the living donors for approximately three quarters of the children, and nearly two-thirds of the children who receive living donor kidneys are Caucasian males. A majority of transplant recipients (39%) are in the age group of 13–17 years followed by 6–12 years (33%). Alport syndrome accounts for 1%–2% of patients reaching ESRD in Europe and 2.3% of the transplant population in the USA.,, The probability of developing ESRD before the age of 30 is >90% in male patients with large rearrangement of COL4A5 or with small mutations leading to premature stop codons.,, The overall rate of progression appears to be slower in male patients with splice site or missense mutations, with a probability of developing ESRD at 30 years in 70% and 50% of patients, respectively. Jais et al. reported on 118 males with Alport syndrome who underwent transplantation. Nearly 2.5% of transplanted male patients developed anti-GBM glomerulonephritis leading to rapid graft loss. All three patients had a large deletion of the COL4A5 gene.,
Living kidney donation in Alport syndrome merits discussion. X-linked AS- related female donors may be asymptomatic carriers and are at risk for ESRD in 15% of cases. It is preferable to do genetic testing. It is preferable to consider those females who do not have genetic mutation. If genetic testing is not available, then urine protein and urine for hematuria should be tested. Women with overt proteinuria, hematuria, and those who display a hearing deficit should be rejected as donors, since they are risk factors for progression to ESRD. Some guidelines suggest a renal biopsy to access the extent of renal damage prior to donation. If a female carrier proceeds with donation, she must be aware of the risks of developing renal failure in later life and should use nephroprotective strategies to minimize the effects of hypertension and proteinuria from the time of surgery.
Individuals from families with autosomal recessive Alport syndrome who have only one of the causative mutations (parents, offspring, some siblings) may be renal donors if they have normal blood pressure, proteinuria levels, and renal function. Genetic testing is recommended.,
Overt posttransplant anti-GBM disease occurs in 3%–5% of Alport syndrome patients. Onset is usually within the 1st year following transplantation. Regular screening for anti-GBM antibodies can be offered, especially if there is an underlying loss-of-function mutation and loss of alpha-5(IV) expression by immunohistochemistry.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Flinter FA, Cameron JS, Chantler C, Houston I, Bobrow M. Genetics of classic Alport's syndrome. Lancet 1988;2:1005-7.
Cangiotti AM, Sessa A, Meroni M, Montironi R, Ragaiolo M, Mambelli V, et al.
Evolution of glomerular basement membrane lesions in a male patient with Alport syndrome: Ultrastructural and morphometric study. Nephrol Dial Transplant 1996;11:1829-34.
Dische FE, Weston MJ, Parsons V. Abnormally thin glomerular basement membranes associated with hematuria, proteinuria or renal failure in adults. Am J Nephrol 1985;5:103-9.
Mallett A, Tang W, Clayton PA, Stevenson S, McDonald SP, Hawley CM, et al.
End-stage kidney disease due to Alport syndrome: Outcomes in 296 consecutive Australia and New Zealand dialysis and transplant registry cases. Nephrol Dial Transplant 2014;29:2277-86.
Magdum PV, Nerli RB, Patil SM, Ghagane SC, Karuppasamy S, Musale A. Early post-transplant ureterovesical junction obstruction managed by an endourological procedure: A case report. J Egypt Soc Nephrol Transplant 2016;16:106. [Full text]
Dixit N, Nerli R, Ghagane S, Hiremath M, Guntaka A. The role of public relation in-charge in kidney transplantation: The cognitions, emotions, ethical, and religious issues in a multicultural society like India. Int J Nephrol Kidney Fail 2015;2. doi: 10.16966/2380-5498.119.
Knebelmann B, Deschenes G, Gros F, Hors MC, Grünfeld JP, Zhou J, et al.
Substitution of arginine for glycine 325 in the collagen alpha 5 (IV) chain associated with X-linked Alport syndrome: Characterization of the mutation by direct sequencing of PCR-amplified lymphoblast cDNA fragments. Am J Hum Genet 1992;51:135-42.
Arrondel C, Deschênes G, Le Meur Y, Viau A, Cordonnier C, Fournier A, et al.
Alarge tandem duplication within the COL4A5 gene is responsible for the high prevalence of Alport syndrome in French Polynesia. Kidney Int 2004;65:2030-40.
Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M. Novel COL4A4 splice defect and in-frame deletion in a large consanguine family as a genetic link between benign familial haematuria and autosomal Alport syndrome. Nephrol Dial Transplant 2003;18:1122-7.
Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, et al.
X-linked Alport syndrome: Natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 2000;11:649-57.
Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F, et al.
Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol 2013;24:364-75.
Gross O, Kashtan CE, Rheault MN, Flinter F, Savige J, Miner JH, et al.
Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: Report from the 2015 international workshop on Alport syndrome. Nephrol Dial Transplant 2017;32:916-24.