Update on Hereditary Kidney Stone Disease and Introduction of a New Clinical Patient Registry in Germany

Abstract

Kidney stone disease is an increasingly prevalent condition with remarkable clinical heterogeneity, with regards to stone composition, age of manifestation, rate of recurrence, and impairment of kidney function. Calcium-based kidney stones account for the vast majority of cases, but their etiology is poorly understood, notably their genetic drivers. As recent studies indicate, hereditary conditions are most likely underestimated in prevalence, and new disease genes are constantly being identified. As a consequence, there is an urgent need of a more efficient documentation and collection of cases with underlying hereditary conditions, to better understand shared phenotypic presentation and common molecular mechanisms. By implementation of a centralized patient registry on hereditary kidney stone disease in Germany, we aim to help closing the vast knowledge gap on genetics of kidney stone disease. In this context, clinical registries are indispensable for several reasons: first, delineating better phenotype–genotype associations will allow more precise patient stratification in future clinical research studies. Second, identifying new disease genes and new mechanisms will further reduce the rate of unknown nephrolithiasis/nephrocalcinosis etiology; and third, deciphering new molecular targets will pave the way to develop drugs for recurrence prevention in severely affected families.

Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients

“…3,13 With the exception of the cohort of patients with urinary stone disease, in which all three patients had mutations in AGXT, the molecular diagnostic rate for each clinical group in our study was slightly higher than, but overall similar to, those that have been previously reported. [3][4][5][6][7][8][9][10][11][12][13][14][15]19 Although research-based genetic testing for most of our patients was performed after kidney transplantation, we identified both retrospective and prospective clinical implications for five patients in whom a molecular diagnosis was established. In 11 cases, identification of a genetic mutation provided a more precise etiological cause for the patient's CKD.…”

“…2 Specifically, a monogenic cause can be identified in 5%-14% of patients with CAKUT, 3-5 11%-30% of patients with SRNS, [6][7][8][9][10] 14% of patients with chronic GN, 11 33%-63% of patients with a renal cystic ciliopathy, [12][13][14][15] and 15%-29% of patients with urinary stone disease. [16][17][18][19] This has important implications for the clinical management of children and young adults with CKD. For example, patients with SRNS who harbor mutations in COQ2, COQ6, or ADCK4 may respond to administration of coenzyme Q 10 , which provides a therapeutic option in an otherwise untreatable disease.…”

Evaluating pathogenicity of SLC34A3-Ser192Leu, a frequent European missense variant in disorders of renal phosphate wasting

“…The index patient was recruited for genetic analysis after informed consent and enrollment in our clinical registry for hereditary kidney stone disorders at the University of Leipzig (Germany) [9]. Patients with idiopathic kidney stone disease were tested for genetic causes after written informed consent and prior study approval by the Institutional Review Board (IRB) of the Universities of Leipzig and Newcastle.…”

Development of a prospective data registry system for retrograde intrarenal surgery in renal stones: Turkish Academy of Urology Prospective Study Group (ACUP study)

“…With the initiations of the registry for hereditary stone disease in Germany, it is expected not only to increase the quality of the management of the patients, but also to determine some of the not yet known genetic properties of this disease. [6] With the primary objective of collecting data for prospective studies, we decided to develop a national, prospective registry specific to stone disease patients undergoing RIRS in various hospitals in Turkey. In this report, we present the development and implementation of this multicentric registry.…”