Differentiating True Nephrotoxicity From Pseudo-nephrotoxicity: A Prospective Comparative Study of Vancomycin Plus Piperacillin-Tazobactam vs. Meropenem Using Serum Creatinine and Cystatin-C
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 304
- 试验地点
- 1
- 主要终点
- To assess the incidence of developing true nephrotoxicity in patients receiving vancomycin + piperacillin-tazobactam versus vancomycin + meropenem.
研究概览
简要总结
This prospective comparative observational study will compare the incidence of true nephrotoxicity in adult patients receiving vancomycin in combination with either piperacillin-tazobactam or meropenem.
Vancomycin plus piperacillin-tazobactam has been associated with a higher incidence of kidney injury based mainly on increases in serum creatinine. However, it remains uncertain whether these increases represent true kidney injury or pseudo-nephrotoxicity, in which serum creatinine increases without a corresponding decline in kidney function.
To address this uncertainty, the study will prospectively assess kidney function using both serum creatinine and cystatin C. True nephrotoxicity will be identified when changes in both biomarkers meet the study criteria for acute kidney injury, while an increase in serum creatinine without a corresponding cystatin C increase will be considered pseudo-nephrotoxicity.
The study will compare true nephrotoxicity between patients receiving vancomycin plus piperacillin-tazobactam and those receiving vancomycin plus meropenem. It will also evaluate the timing, persistence, severity, and recovery of kidney injury. The results may help clarify whether the higher rates of nephrotoxicity reported with vancomycin plus piperacillin-tazobactam represent true renal injury and may help guide antibiotic selection when balancing antimicrobial coverage and kidney safety.
详细描述
Vancomycin is commonly administered in combination with broad-spectrum beta-lactam antibiotics for empiric treatment of serious infections. Several studies have reported a higher incidence of nephrotoxicity in patients receiving vancomycin plus piperacillin-tazobactam compared with vancomycin combined with other antipseudomonal beta-lactams. However, most of these studies have defined kidney injury using serum creatinine alone. This has raised concern that the observed increase in nephrotoxicity may, at least in part, represent pseudo-nephrotoxicity caused by an increase in serum creatinine without a corresponding reduction in true kidney function.
This prospective, non-interventional, comparative two-arm cohort study will evaluate adult patients receiving vancomycin in combination with either piperacillin-tazobactam or meropenem. Treatment selection, antimicrobial dosing, vancomycin therapeutic drug monitoring, fluid management, hemodynamic management, and other clinical decisions will remain under the responsibility of the treating clinical team and will not be determined by the study investigators.
The primary objective is to compare the incidence of true nephrotoxicity between the two treatment groups. Kidney function will be assessed prospectively using both serum creatinine and cystatin C. True nephrotoxicity will be defined as fulfillment of the study criteria for acute kidney injury using both serum creatinine and cystatin C, whereas pseudo-nephrotoxicity will be defined as serum creatinine-based acute kidney injury without a corresponding increase in cystatin C.
Serum creatinine and cystatin C will be assessed at baseline and serially during combination antimicrobial therapy, with additional follow-up measurements after discontinuation when available according to the study protocol. This simultaneous biomarker assessment is intended to help distinguish functional changes in serum creatinine from kidney injury supported by a parallel change in cystatin C.
Secondary assessments will include the time to onset of acute kidney injury based separately on serum creatinine and cystatin C, the incidence of transient and persistent acute kidney injury, kidney recovery, and the severity of acute kidney injury. Kidney recovery and progression to acute kidney disease will also be assessed during follow-up when applicable.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Receipt of vancomycin in combination with either piperacillin-tazobactam or meropenem, with both antimicrobial agents prescribed by the treating physician and expected to be administered concomitantly for >48 hours.
排除标准
- •Known advanced chronic kidney disease (CKD), defined as a baseline estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m², or dialysis dependence..
- •Pregnancy.
- •Receipt of renal replacement therapy prior to enrollment.
- •Obstructive uropathy causing AKI.
- •Recipients of solid organ transplant or hematopoietic stem cell transplantation within one year of presentation
- •Concomitant receive of agents known to be nephrotoxins:
- •Amphotericin B Aminoglycosides Calcineurin inhibitors
- •Patients with AKI 30 days prior to vancomycin initiation
- •Admission to the ICU for indication other than postoperative care for > 72 hours
- •Receiving vancomycin therapy within 30 days before the index combination
研究组 & 干预措施
Vancomycin - Meropenem
Patients who will be receiving a combination of vancomycin and meropenem for treating various types of infections
Vancomycin - Piperacillin Tazobactam
Patients who will be receiving a combination of vancomycin and piperacillin-tazobactam for treating various types of infections
结局指标
主要结局
To assess the incidence of developing true nephrotoxicity in patients receiving vancomycin + piperacillin-tazobactam versus vancomycin + meropenem.
时间窗: From enrollment until 72 hours from stopping vancomycin therapy
True nephrotoxicity is defined as both serum creatinine and cystatin-C meet the AKI criteria on 2026 KDIGO criteria. Serum creatinine-based AKI: defined as any of the following: Change in SCr≥0.3 mg/dL within 48 hours OR SCr≥1.5×baseline within 7 days. Cystatin-C-Based AKI is defined as any of the following: ≥50% increase from baseline cystatin-C OR absolute increase ≥0.3 mg/L from baseline
次要结局
- Difference in time to AKI onset based on serum creatinine and cystatin C between the two groups(From enrollment until 72 hours from stopping vancomycin)
- Incidence of Transient and Persistent Acute Kidney Injury According to the 2026 KDIGO Criteria between the two study groups(From enrollment until 72 hours from vancomycin therapy cessation)
- Recovery from AKI according to the 2026 KDIGO Criteria(From AKI onset through 90 days after AKI onset.)
- Severity of AKI staged according to the 2026 KDIGO criteria between the two groups(From AKI onset through 7 days after AKI onset.)
研究者
Hakeam Abdulaziz Hakeam
Clinical Pharmacy Consultant
King Faisal Specialist Hospital & Research Center