SAT-754 - Reversing the Renal Burden: A Systematic Review and Meta-Analysis of Long-Term eGFR Recovery and Safety Outcomes with Palopegteriparatide in Chronic Hypoparathyroidism

Introduction
Hypoparathyroidism with elemental calcium and active vitamin D analogs can result in hypercalciuria and progressive decline in renal function, especially with long-term use. Palopegteriparatide (Yorvipath), a prodrug of PTH (1-34), was approved in 2025 for the management of hypoparathyroidism and appears to offer kidney protection. Moreover, data suggest improvement in kidney function parameters. To confirm these findings beyond the randomized phases, we performed a systematic review and meta-analysis comparing palopegteriparatide with placebo and natural history cohorts receiving conventional therapy.
Methods
This study was registered on PROSPERO under CRD420251272548 and conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Web of Science databases were searched on 23rd December 2025. Inclusion criteria comprised comparative adult cohort studies assessing parathyroidectomy, comparing preoperative bisphosphonates versus non-bisphosphonates. Variables abstracted included baseline features, bisphosphonate administration, and the main outcome measure of incidence of hungry bone syndrome. Random effects of meta-analysis were conducted whenever at least two relevant studies were found.

Results
Ten studies qualified for inclusion. In randomized therapy, palopegteriparatide improved eGFR at week 26 compared with placebo (MD +9.80 mL/min/1.73 m²; 95% CI 5.12 to 14.48). In treated groups, there was a sustained increase in eGFR: week 52, pooled mean difference +9.29 (95% CI 6.43 to 12.15; I²=0%), week 104 +9.00 (95% CI 6.69 to 11.31), week 156 +8.80 (95% CI 6.08 to 11.52), and week 214 +7.60 (95% CI 4.01 to 11.19). The conventional therapy adjusted annual rate of eGFR decline was −0.64 mL/min/1.73 m²/year (95% CI −0.84 to −0.44). At week 52, urine calcium excretion significantly decreased (MD -100.91 mg/day; 95% CI -170.38 to -31.44; P=0.004; I²=92%).

Conclusion
Across available evidence, palopegteriparatide is associated with early and durable improvement in eGFR and lower urine calcium relative to ULN. This significant finding supports not only the safety, but the beneficial renal effects of palopegteriparatide in the treatment of chronic hypoparathyroidism. Larger comparative studies with standardized renal outcome reporting are needed to validate this outcome.

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