Change in Estimated Glomerular Filtration Rate in Adult Patients With Chronic Hypoparathyroidism Treated With rhPTH(1–84) Compared With a Historical Control Cohort

Abstract

Abstract Chronic hypoparathyroidism (HypoPT) is associated with impaired renal function.1 This study evaluated change in estimated glomerular filtration rate (eGFR) over a 5-yr period in adult patients (pts) with chronic HypoPT treated with or without recombinant human parathyroid hormone (1–84), rhPTH(1–84). The rhPTH(1–84)-treated pt cohort was derived from NCT01297309 (RACE) and NCT01199614 (HEXT) clinical trials. A historical control pt cohort with HypoPT who did not receive rhPTH(1–84) or rhPTH(1–34) were from the large national US Explorys electronic medical record database (Jan 2007−Aug 2019) using criteria similar to the trial enrollment criteria. The index date was the day after treatment initiation for the rhPTH(1–84) cohort and the day after the first calcitriol prescription for the control. The analysis included pts with eGFR ≥60 mL/min/1.73 m2 at the closest eGFR measurement during the 6 months before index date, ≥2 eGFR measurements ≥3 months apart during the 5 yrs on or after the index date and ≥1 eGFR measurement at 5 yrs (±6 months). For pts from RACE, baseline and study visit data after rhPTH(1–84) initiation were collected from the antecedent trials. Changes in eGFR were assessed in linear mixed and multivariable models (adjusted for age/sex/race, baseline eGFR value, history of hypercalciuria/hypertension/type 2 diabetes (T2D)/acute HypoPT manifestations/cardiovascular condition). There were 72 pts in the rhPTH(1–84) cohort and 174 in the control cohort. Before the index date, pts in the rhPTH(1–84) cohort, compared with the control, were younger (mean±SD, 47.5±11.0 vs 53.9±15.5 yrs; P<0.01), and a lower proportion had acute manifestations of HypoPT (22.2% vs 69.0%; P<0.001) and T2D (2.8% vs 17.8%; P<0.001). Over the 5-yr period, the difference in the rate of eGFR change between the 2 cohorts was 1.45 mL/min/1.73 m2 per yr and 1.33 mL/min/1.73m2 per yr, in the unadjusted and adjusted linear mixed models respectively (both P<0.001); eGFR remained higher in the rhPTH(1–84) cohort at all times. Over 5 yrs, eGFR was relatively stable in the rhPTH(1–84) cohort, but eGFR declined in the control at a rate of −1.58 mL/min/1.73 m2 per yr (unadjusted model, P<0.001), and by −1.57 mL/min/1.73 m2 per yr (adjusted model, P<0.001). By yr 5, pts in the rhPTH(1–84) and control cohort were predicted to have eGFR changes from baseline of +1.51 mL/min/1.73 m2 and −10.48 mL/min/1.73 m2, respectively. Data interpretation is limited by the differing pt management (ie, predefined trial protocols and clinical practice for the control). In pts with chronic HypoPT, the annual rate of eGFR decline over a 5-yr period was significantly lower in pts treated with rhPTH(1–84) compared with controls not treated with rhPTH(1–84). These results support the Chen et al1 analysis of data from the same trials and a regional US health record database. 1. Chen KS, et al. JCEM 2020;105(10)dgaa490