Risk of Nephrolithiasis and Nephrocalcinosis in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study

Introduction Chronic hypoparathyroidism managed with conventional treatment, comprising oral administration of calcium and active vitamin D, has been associated with renal complications, including nephrolithiasis and nephrocalcinosis. Further larger-scale studies are needed to examine these risks. This study evaluated the risk of nephrolithiasis and nephrocalcinosis in patients with chronic hypoparathyroidism. Methods A retrospective cohort study using a managed care claims database in the United States from January 2007 to June 2017. Included patients were those with chronic hypoparathyroidism (excluding those receiving parathyroid hormone) and randomly selected patients without hypoparathyroidism over a maximum of 5-year follow-up. The main outcome measures were nephrolithiasis, identified by diagnosis codes or procedure codes for removing kidney stones, and nephrocalcinosis, identified by diagnosis codes. Results The nephrolithiasis analyses included 8097 adult patients with hypoparathyroidism and 40,485 adult patients without hypoparathyroidism. After excluding patients with a diagnosis of nephrocalcinosis at baseline, nephrocalcinosis analyses included 8051 patients with hypoparathyroidism and 40,466 patients without hypoparathyroidism. During 5 years of follow-up, patients with chronic hypoparathyroidism had significantly increased risk of nephrolithiasis and nephrocalcinosis in Kaplan-Meier analysis compared with patients without hypoparathyroidism (both P < 0.001). In the adjusted analyses, chronic hypoparathyroidism was associated with higher risks of nephrolithiasis (hazard ratio [HR], 1.81; 95% confidence interval [CI] 1.60-2.04) and nephrocalcinosis (HR, 6.94; 95% CI 4.41-10.92). A sensitivity analysis restricted to patients with at least one kidney imaging examination showed that 2.6% of patients (n = 59) with hypoparathyroidism and 0.5% of patients (n = 20) without hypoparathyroidism (ratio, 5.5; P < 0.001) developed nephrocalcinosis. Conclusions This large retrospective cohort study showed a statistically significant and clinically meaningful increased risk of nephrolithiasis and nephrocalcinosis in patients who have chronic hypoparathyroidism compared with those who do not have chronic hypoparathyroidism.