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Abstract: TH-PO460

Monogenic Disease Variants in the Swiss Kidney Stone Cohort and Stone-Free Controls

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic


  • Muench, Johannes, Universitat Zurich Physiologisches Institut, Zurich, Switzerland
  • Silva, Joana Figueiro, Institute of Medical Genetics, University of Zurich, Zurich, Switzerland
  • Cabello, Elena María, Institute of Medical Genetics, University of Zurich, Zurich, Switzerland
  • Rubio-Aliaga, Isabel, Universitat Zurich Physiologisches Institut, Zurich, ZH, Switzerland
  • Fuster, Daniel G., Department of Nephrology & Hypertension, University Hospital Bern, Bern, Switzerland
  • Buchkremer, Florian, Division of Nephrology, Cantonal Hospital Aarau, Aarau, Switzerland
  • Wuerzner, Grégoire, Lausanne University Hospital, Service of Nephrology and Hypertension, Lausanne, Switzerland
  • Ritter, Alexander, Department of Nephrology, University Hospital Zurich, Zurich, Switzerland
  • Roth, Beat, Department of Urology, CHUV, University of Lausanne, Zurich, Switzerland
  • Bonny, Olivier, Hopital Fribourgeois, Fribourg, Switzerland
  • Wagner, Carsten A., Universitat Zurich Physiologisches Institut, Zurich, Switzerland
  • Bachmann-Gagescu, Ruxandra, Institute of Medical Genetics, University of Zurich, Zurich, Switzerland

With a lifetime prevalence of 10%, kidney stones (KS) are among the most common diseases. KS disease (KSD) has a complex pathogenesis influenced by a variety of factors, including dietary intake, fluid consumption, metabolic abnormalities, and a genetic predisposition. A thorough understanding of both the genetic and biochemical factors is crucial for a better diagnosis, therapy and prevention. However, data from larger cohorts with KSD with detailed profiling are scare.


The Swiss Kidney Stone Cohort (SKSC) is a multicenter longitudinal observational study consisting of two distinct groups: Kidney stone formers (KSF) and matching non-KSF (NKSF; status confirmed by low-dose CT scan). Blood and urine samples were collected at baseline (KSF, NKSF) and periodically over a 3-year period (KSF). Exome sequencing was performed in all participants, and variants in established KSD genes were assessed according to the ACMG/AMP criteria with subsequent genotype/phenotype analysis for KSF and NKSF.


731 KSF and 201 NKSF were included. A diagnosis of monogenic KSD was established in 10.1% of KSF. (Likely) pathogenic variants were predominantly located in genes encoding proteins involved in phosphate/calcium metabolism (SLC34A1, SLC34A3, ALPL, CYP24A1) or cystinuria (SLC3A1, SLC7A9). Of note, 4.5% of NKSFs also carried (likely) pathogenic variants in KSD genes and displayed matching biochemical parameters (e.g., NKSF with SLC34A1 variants had comparable reduction of TmP/GFR).
In addition, our longitudinal follow-up revealed that among KSFs, patients with monogenic KSD showed a significantly steeper decrease in eGFR over a 36-month period (ΔeGFR -4.9 vs. -2.0 mL/min/1.73 m2, p=0.027).


The SKSC is the hitherto largest genetically analyzed KS cohort, accompanied by a control group of confirmed NKSF. The comparison with NKSFs, who also carried (likely) pathogenic variants in KS genes, suggests that KS occurrence may depend on additional factors that may be either genetic (additional rare or common variants) or environmental. Additionally, the results from genetic analysis in KS genes can help identify patients at higher risk for a faster decline in kidney function.


  • Government Support – Non-U.S.