Hypocitraturia Is an Untoward Side Effect of Synthetic Human Parathyroid Hormone (hPTH) 1-34 Therapy in Hypoparathyroidism That May Increase Renal Morbidity

Subcutaneous human parathyroid hormone (hPTH) therapy can effectively manage hypocalcemia in hypoparathyroidism, with varying effects on hypercalciuria. However, little is known about its ability to decrease the renal comorbidities of hypoparathyroidism: nephrocalcinosis (NC), nephrolithiasis (NL), and renal insufficiency. Urinary citrate (Ucit) promotes the solubility of urinary calcium (UCa); hypocitraturia is a risk factor for NC/NL. Twenty-four-hour UCa, Ucit, and UCa/Ucit were determined in 31 hypoparathyroid subjects receiving hPTH 1-34 therapy for up to 5 years. Before hPTH 1-34, the geometric least squares mean UCa was 346mg/day (normal <250) and Ucit was 500mg/day (normal 250-1190); UCa/Ucit was 0.67mg/mg. After 6 months of hPTH 1-34, UCa decreased (238, p<0.001), but with a greater decrease in Ucit (268, p<0.001), increasing UCa/Ucit, which became significant over time (p<0.001). After stopping hPTH 1-34 and resuming conventional therapy (follow-up; FU), compared to the last measures on hPTH 1-34, Ucit rose to 626 (p<0.001), reducing UCa/Ucit to 0.44, (p<0.05); UCa also rose (273), but was still lower than baseline (p<0.05). Daily hPTH 1-34 dose did not correlate with UCa, but was inversely related to Ucit, and directly related to UCa/Ucit (p<0.01). Mean blood bicarbonate decreased significantly on hPTH 1-34 and remained lower than baseline at FU (p<0.01). Mean eGFR increased on hPTH 1-34 (86 to 96mL/min/1.73m(2), p<0.001) and returned to baseline at FU. On renal imaging, 6 subjects did not have NC/NL, 8 had NC/NL prior to hPTH 1-34 that remained unchanged, and 16 developed new-onset (n=10) or progressive (n=6) NC/NL while on hPTH 1-34. Our data demonstrate that treatment with subcutaneous hPTH 1-34 may have an untoward effect of hypocitraturia and high UCa/Ucit ratio that may increase renal morbidity. With increasing use of PTH therapy in hypoparathyroidism, close monitoring and exploration for treatment of hypocitraturia seem warranted. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.