Safety data on zoledronic acid (ZA) administration for osteoporosis suggest potential kidney toxicity; indeed, it is not indicated in patients with impaired renal function. Patients clinical monitoring usually includes glomerular filtration rate (GFR) evaluation; no study addressed the issue of the early kidney injury. We evaluated the early (within 3 months) effect of iv ZA on renal function defining the potential role of AKI biomarkers in unveiling subtle damage.
Five mg i.v. ZA infusion was administered for the first time to 23 patients with osteoporosis and normal renal function (17 women and six men, mean age 73±7 S.D. years). AKI biomarkers (urinary (u) NGAL, KIM-1, and MCP-1; serum (s) MCP-1 and IL-18) were assessed at baseline and at day (d) 2 and 30 after administration. Creatinine clearance (CrCl), plasma C-terminal FGF-23, sKlotho, calcium excretion (CaEx) and renal threshold phosphate concentration/GFR (TmPO4/GFR) were also measured.
No significant changes in mean levels of urinary markers were detected. Mean values of sIL-18 and sMCP-1 significantly increased at d 2 (44±88%; P<0.01 and 198±237%; P<0.001) and returned to baseline levels at d 30. Mean CrCl values did not significantly change at d 30. We observed no difference in mean levels of plasma C-terminal FGF-23 and sKlotho at any time. There was a 28±59 and 26±43% decrease in CaExcr at d 2 (P<0.05) and d 30 (P<0.01), respectively. TmPO4/GFR significantly decreased at d 2 and d 30 (−8.6±15.9%, P<0.05 and −11.3±13.5%, P<0.001).
Our data show that there is an acute renal damage as early as 24 h after ZA infusion in osteoporotic patients with normal renal function. Renal injury is apparently reversible after 1 month. Secondary hyperparathyroidism could be responsible for reduction in TmPO4/GFR and calcium excretion.
14 May 2016 - 17 May 2016