Abstract: SA-PO0167
LRP5-Associated Recurrent Nephrolithiasis: A Metabolic Stone Phenotype
Session Information
- Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Ruiz, Analisa, Geisinger Medical Center, Danville, Pennsylvania, United States
- Dupont, Julian Henri, Geisinger Medical Center, Danville, Pennsylvania, United States
- Kalra, Kartik, Geisinger Medical Center, Danville, Pennsylvania, United States
Introduction
LRP5 is central to Wnt signaling, bone formation, and calcium handling. Heterozygous pathogenic LRP5 variants are associated with high bone mass and increased intestinal calcium absorption, which may result in hypercalciuria and nephrolithiasis. Stone disease in this setting appears metabolic rather than structural.
Case Description
A 35-year-old man with early-onset, recurrent nephrolithiasis presented for prevention management. He reported multiple stone passages and several urologic procedures. Stone analysis showed calcium oxalate stones in 2025 and uric acid-predominant stones (80% in 2020; 50% in 2021). Imaging demonstrated bilateral nephrolithiasis. Kidney function remained preserved. Given longstanding disease and strong family history, genetic testing was obtained and revealed a heterozygous LRP5 variant (c.3245A>G; p.Tyr1082Cys). Metabolic evaluation revealed low urine volume (1.54 L/day), hypercalciuria (342 mg/day), hypocitraturia (198 mg/day), and low urine pH (5.5). Supersaturation indices were elevated for calcium oxalate (3.24) and uric acid (2.83). Urinary sodium was elevated (194 mmol/day), supporting a dietary contribution to hypercalciuria. Oxalate and uric acid excretion were within range. The overall profile was consistent with hypercalciuric, hypocitraturic nephrolithiasis with mixed calcium oxalate and uric acid stone risk. He was counseled on increased fluid intake, low sodium and oxalate diet, normal dietary calcium intake, and avoidance of excess calcium or vitamin D supplementation. Potassium citrate and allopurinol were continued, a thiazide diuretic was initiated, and DEXA scan was considered.
Discussion
This case highlights a suspected genetic contribution to recurrent nephrolithiasis via altered calcium handling rather than structural kidney disease. Recognition of LRP5-related stone disease has implications for targeted metabolic management, genetic counseling, and consideration of bone phenotyping, including DEXA scan. Review of ClinVar and published literature shows this variant reported in the heterozygous state within a single family with early-onset osteoporosis; functional consequences are incompletely characterized, with some databases listing the variant as one of uncertain significance. Broader awareness of genetic stone disorders may improve individualized prevention strategies in patients with early-onset or refractory nephrolithiasis.