Abstract

Background: Chronic hypoparathyroidism (HypoPT) managed with conventional therapy (i.e., oral calcium and active vitamin D) may potentially increase the risk of chronic kidney disease (CKD) stage ≥ 3 and accelerate CKD stage progression, including progression to end stage kidney disease (ESKD) (i.e., CKD stage 5 or dialysis). Methods: A retrospective cohort study was conducted to compare the risk of CKD between chronic HypoPT patients (excluding those receiving parathyroid hormone) and randomly selected non-HypoPT patients over 5 years of follow-up using a large US commercial claims database (Q1 2007 - Q2 2017). The first date of follow-up (i.e., index date) for HypoPT patients was the earliest HypoPT diagnosis date at least 6 months after the initial HypoPT diagnosis and for non-HypoPT patients was the date of a randomly selected medical claim. Patient characteristics at baseline (the 6 months prior to index date) were compared between cohorts. CKD stages were identified by diagnosis codes, estimated glomerular filtration rate (eGFR) lab values (calculated using the CKD-EPI formula), and dialysis procedure codes. Among those free of CKD at baseline, the risk of incident CKD stage ≥ 3 was compared between cohorts using Kaplan-Meier analysis and adjusted Cox proportional hazards models. Adjusting parameters included demographic (age, sex, race, region, and index year) and clinical (heart failure, hypertension, diabetes, and medication use) characteristics at baseline. Similar analyses were conducted for CKD progression to a higher CKD stage and to ESKD, among patients with baseline CKD stages 3 or 4. Results: A total of 8,097 chronic HypoPT and 40,485 non-HypoPT patients were included. Compared to non-HypoPT patients, HypoPT patients were older (58.6 vs. 47.3 years), a higher proportion were female (76.2 vs. 54.4%), and a higher proportion had CKD stages 3-5 (16.4 vs. 3.0%) and stages 3-4 (13.6 vs. 2.6%) at baseline. Among those with baseline CKD stages 3-4, HypoPT patients were younger (70.6 vs. 72.1 years) and a higher proportion were female (67.1 vs. 54.8%) compared to non-HypoPT patients. Kaplan-Meier analyses showed that HypoPT patients had significant increased risk of CKD stage 3 and higher, CKD progression, and progression to ESKD compared to non-HypoPT patients (all p<0.001). The adjusted hazard ratios (HRs) associated with HypoPT vs. non-HypoPT were 2.57 (95% confidence interval [CI]: 2.35, 2.82) for CKD stage ≥ 3, 1.62 (1.29, 2.03) for CKD progression, and 1.95 (1.41, 2.70) for progression to ESKD (all p<0.001). Conclusions: Chronic HypoPT was associated with significant increased risk of CKD stage ≥ 3 and CKD stage progression, including progression to ESKD. Further research is warranted to understand the potential mechanisms for the relationship of chronic HypoPT and its management with these observed risks. Funding: Shire

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