MON-766 Risk Factors for Renal Stone Development in Adults with Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis

Abstract Disclosure: M. Jay: None. S. Andrei: None. P. Hoang: None. A. Samani: None. T. Anpalagan: None. H. Samhat: None. D. Nguyen: None. R. Jones: None. R. Fu: None. N. Villemure-Poliquin: None. G. Gore: None. L.L. Lipscombe: None. A. Eskander: None. Background: Renal stones (RS) are a common complication of primary hyperparathyroidism (PHPT), posing significant clinical and economic burdens. Identifying RS risk factors is crucial for targeted prevention, monitoring, and prioritizing parathyroidectomy. However, no systematic review has evaluated RS risk factors in PHPT. Objective: We evaluated prespecified risk factors (age, sex, serum calcium, parathyroid hormone [PTH], vitamin D, and urine calcium) for incident and recurrent RS in adults with PHPT. Methods: We searched MEDLINE, Embase, and Cochrane CENTRAL through September 2024. Two reviewers independently selected cohort, case-control, and cross-sectional studies involving adults (≥18 years) with PHPT, excluding clinical trials, abstracts, and case reports. We extracted data on participants, risk factors and RS outcomes. Random-effects meta-analyses estimated adjusted (aOR) and crude (cOR) odds ratios. We used the Quality in Prognostic Studies and GRADE frameworks to assess risk of bias and evidence certainty, respectively. Sensitivity analyses excluded cross-sectional and high-risk-of-bias studies. Subgroup analyses explored heterogeneity by design, risk of bias, and osteoporosis. Meta-regression assessed serum calcium’s effect on other risk factors. The protocol was registered in PROSPERO (CRD42024608180). Results: Of 5,925 records, 53 studies (N=40,310; 8,311 RS cases) were included; 36 were cross-sectional. Median age was 58.4 years (IQR 55.7-61.9), and 77.9% were female (IQR 72.6-81.6). High-certainty evidence indicated male sex (aOR 2.04; 95% CI, 1.67-2.56; I² = 0%, N = 5 studies, 3,793 patients) and elevated urine calcium (aOR 2.38; 95% CI, 1.65-3.46; I² = 37.9%, N = 6 studies, 3,345 patients) were associated with increased RS risk. Moderate-certainty evidence suggested that younger age was associated with increased recurrent RS (uOR 12.50; 95% CI, 4.55-33.33; I² = 89.3%, N = 4 studies, 2,910 patients). Associations with serum calcium (aOR 1.42; 95% CI, 0.66-3.05; I² = 67.3%, N = 4 studies, 8,189 patients), PTH (aOR 0.99; 95% CI, 0.82-1.20; I² = 0%, N = 3 studies, 1,883 patients), and vitamin D (cOR 1.14; 95% CI, 0.71-1.81; I² = 61.8%, N = 12 studies, 2,274 patients) were informed by low- or very low-certainty evidence. Findings were consistent across sensitivity analyses. No subgroup differences emerged, and meta-regression found no modifying effect of serum calcium. Discussion: Our findings establish a distinct RS risk profile in PHPT compared with the general RS population. Male sex and elevated urinary calcium are key RS risk factors in PHPT, while younger age is pertinent to recurrence. These results support vigilant RS surveillance and timely parathyroidectomy in high-risk patients. Further research should refine RS risk factors, differentiate incident from recurrent RS, and assess the impact of early parathyroidectomy on RS morbidity and costs. Presentation: Monday, July 14, 2025