Genetics of Monogenic Kidney Stone Disease (KSD): A review

Abstract

Kidney stone disease (KSD) is a multifactorial illness characterized by a complex combination of hereditary and environmental variables. It generates enormous morbidity and medical care costs all over the globe. The majority of kidney stones are calcium-based, and they are frequently accompanied with a metabolic imbalance such as hypercalciuria. The effort to discover causal genes will offer a better knowledge of the pathophysiology of KSD. This will result in enhanced patient care quality and efficiency, as well as illness and complication detection, prevention, and control. This article reviews the understanding of documented monogenic KSD, as well as an update on molecular genetic investigations to examine genes responsible for the illness. Nephrolithiasis (kidney stone disease) is a prevalent issue that may be linked with changes in urine solute composition, including hypercalciuria. According to studies, approx. 15% of patients visiting kidney stone clinics had monogenic kidney stone illnesses such as renal tubular acidosis with deafness, Bartter syndrome, primary hyperoxaluria, and cystinuria. Genetic approaches to studying monogenic factors in nephrolithiasis have revealed that transporters and channels; ions, protons, and amino acids; the calcium-sensing receptor (a G protein-coupled receptor) signaling pathway; and the metabolic pathways for vitamin D, oxalate, cysteine, purines, and uric acid all play important roles in the aetiology of kidney stones. For NGS diagnoses of hereditary KSD, a complete gene panel is recommended. Accurate and timely diagnosis of hereditary forms of urolithiasis allows for the identification of a pathological germinal mutation and accurate diagnosis, analysis of heterozygous mutation carriage in affected families and evaluation of the prognosis of KSD development in family members, and personalized management of KSD patients.