Background: Chronic kidney disease of undetermined etiology is common and poses a substantial problem for patients undergoing renal transplant surgery. We aim to utilize next generation sequencing in a single center to discover the genetic etiology in patients undergoing prospective renal allograft transplant.
Methods: In this observational cross-sectional study, all the patients with chronic kidney disease of undetermined etiology undergoing renal transplant surgery, irrespective of age and gender were included. Clinical indications for genetic testing were categorized as glomerular diseases, nephrolithiasis, tubulopathies, cystic kidney diseases and others. Next generation sequencing was used for genetic analysis. The pathogenicity of the genetic variant was interpreted as per the American College of Medical genetics classification.
Results: A total of 56 samples of patients with chronic kidney disease of undetermined etiology were sent for genetic testing. A total of 45 variants of mutated genes were reported in 37 patients. Out of 45 variants, 32 were missense, 8 were deletion, 3 were nonsense and 1 was splice site mutation. Thirty-four were heterozygous, 6 were homozygous and 2 were hemizygous variants. Nine patients (20%) had pathogenic and 6 (13.33%) had likely pathogenic variants. Twenty-nine patients (64.44%) had variants of uncertain significance. No genetic mutations were reported in 18 patients (32.14%). A genetic diagnosis was made in 15 patients with overall yield of 26.78%. The diagnostic yield was 40% for glomerular disorder, 100 % for tubular disorder, 50% for renal calculi disease and 18.42% for patients with chronic kidney disease of unknown etiology. Genetic testing made a new diagnosis or changed the diagnosis in 6 patients (10.71 %).
Conclusion: Nearly one third (26.78%) of the patients with chronic kidney disease of undetermined etiology who underwent gene study were tested positive for a genetic disease. Genetic testing confirmed the clinical diagnosis, changed the clinical diagnosis or made a new diagnosis, which helped in making better treatment strategies for the patients.