Pharmacokinetics of Zoledronic Acid in Patients on Dialysis

Summary

Osteoporosis is a frequent complication of chronic kidney disease (CKD) on dialysis, with an estimated prevalence of approximately 40%. It is associated with increased fracture risk, reduced quality of life, and higher mortality. Despite available therapies, management often remains suboptimal, partly due to limited evidence on the safety and pharmacokinetics of bisphosphonates in this population. Objectives: To understand the pharmacokinetics of zoledronic acid in CKD patients on dialysis, as well as to analyze its effects on biomarkers of bone metabolism, bone mineral density (BMD), and clinical outcomes. Materials and Methods: This prospective clinical study involves 24 adult individuals, 8 with CKD-associated osteoporosis (control group; estimated glomerular filtration rate (eGFR) ≥ 35 mL/min/1.73 m²) and 16 with CKD-associated osteoporosis anuric on dialysis patients. Individuals undergoing dialysis will be assigned to receive zoledronic acid at doses of 2.5 mg or 5 mg intravenously (single dose, at the beggining of dialysis session), while patients with CKD-associated osteoporosis (control group; estimated glomerular filtration rate (eGFR) ≥ 35 mL/min/1.73 m²) will receive 5 mg, also in a single dose. Serial blood samples will be collected after infusion, during dialysis session and again up to 96h after dialysis session initiation. The dialysate will be continuously sampled in a tank and aliquots collected for further analysis. The plasma levels of zoledronic acid will be calculated from blood and dialysate samples using liquid chromatography mass spectrometry. The primary outcome is the plasma concentration-time curve of zoledronic acid during a regular dialysis session. Secondary outcomes are: (i) plasma concentration of zoledronic acid up to 96h;(ii) the total mass of zoledronic acid extracted by the dialysate; (iii) the dialytic clearance of zoledronic acid. Evaluation of bone biomarkers (e.g., PTH, alkaline phosphatase, calcium, phosphorus, CTX, and P1NP) and BMD (assessed by bone densitometry) will be performed at baseline and at 12 months. The study will be conducted at the UNICAMP Clinical Hospital, with the participation of one participating center, subject to prior approval from the respective Research Ethics Committees. All participants will be included only after signing the Informed Consent Form. Data will be anonymized and processed in accordance with the General Data Protection Law (LGPD). Expected results: To characterize the pharmacokinetic profile and establish the best dosage regimen of zoledronic acid in patients with CKD on dialysis; to observe the impact of the drug on biomarkers of bone metabolism and BMD.

Conditions

• Chronic Kidney Disease
• Osteoporosis
• Dialysis

Interventions

DRUG

Zoledronic Acid Injection, 5.0 mg, single dose

Zoledronic Acid Injection, 5.0 mg, single dose for patients with CKD-associated osteoporosis with eGFR \>= 35 mL/min.

DRUG

Zoledronic Acid Injection, 2.5 mg, single dose

Zoledronic Acid Injection, 2.5 mg, single dose, for patients with CKD-associated osteoporosis on dialysis, at the beginning of dialysis session.

DRUG

Zoledronic Acid Injection, 5.0 mg, single dose

Zoledronic Acid Injection, 5.0 mg, single dose, for patients with CKD-associated osteoporosis on dialysis, at the beginning of dialysis session.

Sponsors & Collaborators

• São Paulo State University

  collaborator OTHER

• University of Campinas, Brazil

  lead OTHER

Principal Investigators

• Rodrigo B de Oliveira, PhD · University of Campinas

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-15

Primary Completion

2027-08-15

Completion

2028-08-15

Countries

• Brazil

Study Locations