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Abstract Background and Aims Chronic kidney disease (CKD), impacting over 850 million people worldwide, is a diverse group of inherited and acquired nephropathies. While only about 10% of adult CKD is hereditary, predominantly due to mutations in genes like PKD1, PKD2, and PKHD1, the etiology often remains unidentified, leading to challenges in management, especially in transplantation and genetic counseling contexts. This study used whole exome sequencing to investigate CKD of unknown origin, aiming to improve diagnostic yields and establish genetic associations. Our objective was to find the diagnostic yield of Whole exome sequencing in patients with CKD of unknown etiology and to establish genetic association for same. Method The study was conducted in the Department of Nephrology and the Institute of Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi. It was an observational cross-sectional analysis. All patients, both male and female of all age groups with Chronic Kidney Disease of unknown etiology who were willing to participate. All patients, both male and female of all age groups with Chronic Kidney Disease of known etiology were excluded as following: Results In the investigation of 56 chronic kidney disease samples with unknown etiology, genetic testing yielded 45 mutated gene variants in 37 subjects. The variants comprised 32 missense mutations, 8 deletions, 3 nonsense mutations, and 1 splice site mutation. Variant zygosity was as follows: 34 heterozygous, 6 homozygous, and 2 hemizygous. Pathogenic variants were detected in 9 patients (20%), likely pathogenic in 6 (13.33%), and variants of uncertain significance in 29 (64.44%). Eighteen subjects (32.14%) demonstrated no genetic mutations. A genetic diagnosis was established in 15 patients, representing a diagnostic yield of 26.78%. Stratified by disorder, the yield was 40% for glomerular, 100% for tubular, 50% for renal calculi, and 18.42% for undetermined CKD. Genetic testing facilitated a novel diagnosis or an alteration of the existing diagnosis in 6 patients (10.71%). Conclusion The results affirm the efficacy of genetic testing in elucidating the etiologies of chronic kidney disease where traditional diagnostic methods do not yield definitive causation. Genetic alterations were identified in a significant proportion of the patient population, indicating the presence of underlying genetic contributors to the disease. The identification of pathogenic and likely pathogenic variants highlights the potential of genetic testing to impact clinical decision-making and patient care.
Tiwari et al. (Wed,) studied this question.