Prevalence of genetic mutations associated with kidney disorders in renal transplant recipients – single centre experience
Ankur Mittal1, Abhijit Konnur1, Sishir Gang1, Mohan Rajapurkar1, Umapati Hegde1, Hardik Patel1, Shailesh Soni2, Sachidanand Panday2.
1Nephrology, Muljibhai Patel Urological hospital, Nadiad, India; 2Pathology, Muljibhai Patel Urological hospital, Nadiad, India
Introduction: End-stage renal disease (ESRD) of undetermined etiology is highly prevalent and constitutes a significant clinical challenge, particularly in the context of kidney transplantation. Underlying renal conditions leading to ESRD are extremely heterogeneous and the prevalence of hereditary nephropathies among adults with ESRD is less known. To date, less than 10% of adult ESRD is thought to be genetic. Genetic analysis often reveals the cause of kidney failure in patients with unknown kidney disease. For patients awaiting renal transplantation, genetic testing prior to kidney transplant may help to understand the outcome in these patients. We studied the prevalence of genetic mutations related to kidney disease in renal transplant (RTx) recipients.
Methods: It was a Single Centre, Observational, Cohort Study. Between October 2019 & July 2021, 123 RTx recipients were analyzed using Multiplex Ligation-dependent Probe Amplification (MLPA) and clinical exome sequencing for mutations related to kidney disease.
Results: Mean age was 36±12 years, 96 (78%) were Males. 88 (71.5%) were undetermined and 35 (28.4 %) had established cause of CKD. 8 patients had structural or hereditary kidney disease and 27 were non-hereditary including DKD, Glomerulopathy, Obstructive uropathy and CTID diagnosed by kidney biopsy and clinical and radiological presentations. 17/88 (19.3%) patients with undetermined CKD on renal biopsy showed Glomerulosclerosis (6), CGN (8) & TMA (2). one had advanced renal damage. 32/88 (36.36%) patients had genetic mutations related to kidney disease. 20 were structural congenital or hereditary kidney disease & 10 had a mutation for Glomerulopathies.
Mutations related to complement regulatory genes were found in 84/123 (68.2%). 6 patients had congenital or hereditary kidney disease, 12 were DKD, 5 were Glomerulopathy, 2 had Obstructive Kidney disease and 1 had CTID. Homozygousity and heterozygosity were seen in 14 (16.8%) and 10 (12%) patients respectively. 67/88 (80.7%) also showed CFHR1/CFHR3 gene complex duplication, reported as a variant of uncertain significance. 1 patient had a mutation for the PLG gene, previously been implicated in the pathogenesis of ahus.
Conclusion: This study demonstrates 82.9% (102/123) prevalence of the genetic mutation in RTx recipients. Genetic analysis provides the etiology in 35 patients with undetermined kidney disease. The significance of complementary regulatory gene related mutation remained uncertain.
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