Endocrine Abstracts

Introduction: Hypoparathyroidism (Hypo) is associated with a higher risk of chronic kidney disease (CKD) and renal stones, although the time to onset of these complications in the disease’s natural history has never been explored. Calcium-Phosphate product (CaxP) has been shown to be a risk factor for moderate renal disease in Hypo in a limited number of cross-sectional or case-control studies.

Objective: To determine the time of onset of incident severe CKD and nephrolithiasis and their biochemical predictors in a cohort of Hypo patients treated with conventional therapy.

Design: Longitudinal retrospective study with review of paper and electronic medical records over 40 years.

Setting: Single academic medical center.

Patients: 203 patients with chronic hypoparathyroidism who were regularly followed between 1980 and 2023 in an outpatient setting.

Main outcome measures: Demographic and biochemistries, time to first incident GFR<30 ml/min and time to first incident nephrolithiasis diagnosed clinically or radiologically.

Results: Mean age at last follow-up was 61 years [range, 20-93], with most patients having post-surgical Hypo (94.1%), predominantly women (79.3%), with a median disease duration of 11 years (range 0-50 years). The time-weighted average (TWA) of serum calcium was 8.4±0.8 mg/dl, TWA serum phosphate was 4.4±0.8 and the TWA CaxP was 38.2 [range, 23-47] mg²/dl², while TWA urinary calcium was normal at 126 mg/day [range, 118-233]. Twenty-five (12.3%) patients experienced a GFR decline to less than 30 ml/min. In a Kaplan-Meier analysis, mean time from diagnosis to first GFR<30 ml/min was 38.6 years [33.9-43.3]95%CI. A shorter time to CKD was associated with greater CaxP (HR 45, P=0.043) and longer duration of Hypo (HR 16.9, P>0.001) in a Cox-regression model (P>0.001) independent of hypertension, TWA calcitriol dosage and TWA calcium supplements doses. Thirty-two (15.8%) patients experienced asymptomatic incident kidney stones. Mean time to first incident nephrolithiasis was estimated to be 36.6 years [31.7-41.7] 95%CI in a Kaplan-Meier analysis. In a Cox-regression model (P>0.001) adjusted for TWA urinary calcium, TWA calcitriol dosage, sex and TWA calcium supplements doses, a higher CaxP (HR 1.76, P=0.048) and longer duration of Hypo (HR 4.26, P>0.001) were the only significant predictors of early kidney stones.

Conclusions: In a predominantly post-surgical cohort of Hypo, a higher CaxP product accelerates the onset of severe CKD and nephrolithiasis despite averagely well biochemical control. A lower CaxP target than 55 mg²/dl² might be considered to delay future renal disease in chronic hypoparathyroidism.