Study: Natpara Prevents Kidney Insufficiency Long-term in Hypoparathyroidism
While people with hypoparathyroidism receiving conventional treatment with supplements experience significant declines in kidney function over time, the replacement therapy Natpara appears to preserve kidney function in the long-term, a five-year analysis shows.
The study, “5-Year Estimated Glomerular Filtration Rate in Patients with Hypoparathyroidism Treated with and Without rhPTH(1-84),” was published in The Journal of Clinical Endocrinology and Metabolism.
The conventional treatment for hypoparathyroidism consists of calcium and vitamin D supplementation to restore calcium back to normal levels, but evidence suggests that raising calcium levels without increasing PTH may cause kidney insufficiency in the long run.
Natpara, sold as as Natpar in Europe, is a synthetic form of PTH that is approved in the U.S. in combination with calcium and vitamin D supplements for people whose hypoparathyrodism cannot be controlled effectively with supplements only.
Developed by Shire — now part of Takeda — the therapy helps patients maintain acceptable calcium levels while reducing their supplement doses, but studies to date have not assessed the impact of Natpara on long-term kidney function.
To address this gap in knowledge, a team including researchers at Shire compared changes in kidney function over five years between people with chronic hypoparathyroidism receiving Natpara and a group not taking the therapy.
The Shire-funded study included 69 patients who received Natpara in four open-label trials and 53 controls from the Geisinger Healthcare Database who were not treated with Natpara.
The four Natpara studies were REPLACE (NCT00732615) and RELAY (NCT01268098), their extension Phase 3 study, RACE (NCT01297309), and a Phase 4 trial (NCT02910466) that examined the long-term safety of Natpara, as well as its effect on calcium control and quality of life.
Compared to controls, Natpara patients were younger (48.2 vs. 55.8 years), and had history of hypocalcemia — low calcium levels — type 2 diabetes, and cardiac diseases less frequently. Use of concomitant medications also was less common in the Natpara group. Kidney function and calcium levels, however, were similar between the two groups.
Over the five years of follow-up, people on Natpara had a median of 17 readings of their estimated glomerular filtration rate (eGFR, a measure of kidney function). Controls had a median of 58 eGFR measures.
After adjusting for confounding measures, such as age, sex, medical history, medication use and initial eGFR scores, the researchers found that controls experienced a decline in kidney function by 8 milliliters per minute (8 mL/min) and 1.73 m² (correction for body surface area), while kidney function increased by 2.8 mL/min/1.73 m² over five years among those taking Natpara.
Overall, patients not receiving Natpara experienced an annual 1.7 mL/min/1.73 m² decline in kidney function scores compared to people given the medication — a significant difference.
“eGFR was preserved over 5 years among patients with chronic HypoPT [hypoparathyroidism] receiving rhPTH(1-84) [Natpara] treatment, contrasting with an eGFR decline among those not receiving rhPTH(1-84),” the researchers wrote.
“Further research with a prospective experimental design is needed to substantiate these findings and to reveal putative underlying mechanisms for how PTH replacement may preserve kidney function in HypoPT,” they concluded.