Introduction:
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 centre to discover the genetic etiology in patients with Chronic Kidney Disease of undetermined etiology.
Methods:
In this observational cross-sectional study, all the patients with chronic kidney disease of undetermined etiology, 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. The aim of the study is to find the diagnostic yield of NGS (Next generation sequencing) and it's outcome.
Results:
A total of 100 samples of patients with chronic kidney disease of undetermined etiology were sent for genetic testing. A total of 77 variants of 49 mutated genes were reported in 61 patients. Out of 77 variants, 53 were missense, 17 were deletion, 4 were nonsense, 2 were duplication, 5 were splice site and 4 were copy number variants (CNV). Thirty three (42.85%) each had an autosomal recessive and autosomal dominanat inheritance, 3 (3.89%) each had X linked dominant and X linked recessive inheritance and 1 had mitochondrial pattern of inheritance. Twenty-one patients (21%) had pathogenic and 5 patients (5%) had likely pathogenic variants and 51 were variant of unknown significance (VUS). No genetic mutation were reported in 39 patients (39%). A genetic diagnosis was made in 26 patients with overall yield of 26%. By disease category, the diagnostic yield was 57.14% in cystic renal diseases (4 of 7 patients), 100% in tubular diseases (2 of 2 patients), 37.5% in glomerular diseases (3 of 8 patients), 33.33% in congenital anomaly of kidney and urinary tract (2 of 6 patients), 25% in renal calculi disease (3 of 12 patients) and 18.46% of Chronic kidney disease of undetermined etiology (12 of 65 patients). In 12 patients (12%) genetic testing provided a new diagnosis. It revised the clinical diagnosis in 6 patients and confirmed the clinical diagnosis in 8 patients.
Conclusions:
Nearly one third (26%) of the 100 patients with chronic kidney disease of undetermined etiology underwent gene study and 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.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.