Risk of Chronic Kidney Disease and Estimated Glomerular Filtration Rate Decline in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study

Abstract

Introduction: Chronic hypoparathyroidism, treated with conventional therapy of oral calcium supplements and active vitamin D, may increase the risk of kidney complications. This study examined risks of development and progression of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) decline 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 with chronic hypoparathyroidism (excluding those receiving parathyroid hormone) and randomly selected patients without hypoparathyroidism followed for up to 5 years. Main outcome measures were (1) development of CKD, defined as new diagnosis of CKD stage 3 and higher or ≥ 2 eGFR measurements < 60 ml/min/1.73 m² ≥ 3 months apart, (2) progression of CKD, defined as increase in baseline CKD stage, (3) progression to end-stage kidney disease (ESKD), and (4) eGFR decline ≥ 30% from baseline. Time-to-event analyses included Kaplan-Meier analyses with log-rank tests, and both unadjusted and adjusted Cox proportional hazards models were used to compare outcomes between cohorts.

Results: The study included 8097 adults with and 40,485 without chronic hypoparathyroidism. In Kaplan-Meier analyses, patients with chronic hypoparathyroidism had higher risk of developing CKD and CKD progression and higher rates of eGFR decline (all P < 0.001). In multivariable Cox models adjusted for baseline characteristics, hazard ratios (95% confidence intervals [CIs]) were 2.91 (2.61-3.25) for developing CKD, 1.58 (1.23-2.01) for CKD stage progression, 2.14 (1.51-3.04) for progression to ESKD, and 2.56 (1.62-4.03) for eGFR decline (all P < 0.001) among patients with chronic hypoparathyroidism compared with those without hypoparathyroidism.

Conclusion: Patients with chronic hypoparathyroidism have increased risk of development and progression of CKD and eGFR decline compared with those without hypoparathyroidism. Further studies are warranted to understand underlying mechanisms for the associations between chronic hypoparathyroidism and kidney disease.

Keywords: Active vitamin D; Calcium; Chronic hypoparathyroidism; Chronic kidney disease; End-stage kidney disease.

Fig. 1

Sample selection of patients a with and b without chronic hypoparathyroidism. CKD chronic kidney disease, eGFR estimated glomerular filtration rate, HypoPT hypoparathyroidism, rhPTH(1–84) recombinant human parathyroid hormone (1–84). *Patients were required to have ≥ 1 eGFR measurement during the baseline period and ≥ 2 eGFR measurements at least 3 months apart during the study period. The index date of the study period was the first date of a diagnosis of hypoparathyroidism at least 6 months after initial diagnosis for the cohort of patients with hypoparathyroidism and the date of an eligible, randomly selected claim for the cohort of patients without hypoparathyroidism. In both cohorts, the baseline period was defined as the 6 months before the index date

Fig. 2

Time to first instance of a CKD stages 3–5^a, b CKD stage progression^b, and c progression to ESKD^c. CKD chronic kidney disease, eGFR estimated glomerular filtration rate, ESKD end-stage kidney disease, HypoPT hypoparathyroidism. ^aDefined as the first instance of CKD stages 3–5 defined by diagnosis codes and by ≥ 2 eGFR measurements < 60 ml/min/1.73 m² at least 3 months apart on or after the index date among patients without CKD stage 3 or 4, ESKD, or unspecified CKD during the baseline period. ^bDefined as CKD stage progression in those with CKD stages 3 and 4 at baseline to a higher CKD stage, as indicated by either a diagnosis code for a higher CKD stage or ≥ 2 eGFR measurements at least 3 months apart both representing a higher CKD stage. ^cDefined as the first instance of ESKD by either a diagnosis code for CKD stage 5 or ≥ 2 eGFR measurements < 15 ml/min/1.73 m² at least 3 months apart on or after the index date among patients with CKD stage 3 or 4 during the baseline period

Fig. 3

Time to first eGFR decline ≥ 30% from baseline for all patients. eGFR estimated glomerular filtration rate, HypoPT hypoparathyroidism

Fig. 4

Time to first eGFR decline ≥ 30% from baseline for patients with eGFR a < 60 ml/min/1.73 m² and b ≥ 60 ml/min/1.73 m² at baseline. eGFR estimated glomerular filtration rate, HypoPT hypoparathyroidism