Quantifying the impact of vancomycin on short and long term renal function in a contemporary real-world pediatric stem cell transplant cohort Free

As survival rates after pediatric hematopoietic cell transplant (HCT) continue to improve, reducing toxicity and maximizing organ function outcomes become ever more attainable goals. Since children undergoing HCT are at risk of renal injury due to frequent exposures to nephrotoxic antimicrobials, understanding the impacts of antimicrobials and other nephrotoxic supportive care agents on long term renal outcomes is critical. Commonly used agents such as vancomycin, amphotericin, cidofovir, and others are effective at combating life-threatening infections in transplant recipients, but the tradeoff in short- and long-term renal injury may be significant. The real-world effect of nephrotoxic antimicrobials on renal function outcomes has not been well characterized in a contemporary real-world pediatric transplant cohort. Our study focuses first on one of the most commonly-used nephrotoxins, vancomycin, as we quantify acute kidney injury (AKI) events and long term renal function based on degrees of vancomycin exposure.

We conducted a single center retrospective chart review of consecutive pediatric HCT recipients from 2018-2024, merging detailed clinical records from a REDCap database with infection history, antimicrobial exposures, and serial measures of renal function. Renal function was quantified via estimated glomerular filtration rate (eGFR) using the U25 CKiD calculator. eGFR values were capped at 120 for the purposes of data analysis. Renal function was described at days +100 and +365 post-HCT by the following 2 methods: 1) eGFR within the range of CKD stages 2-5, and 2) a decline in eGFR of at least 50% from the pre-HCT baseline. AKI was defined using both standard KDIGO criteria: 1) an increase in serum creatinine ≥0.3 mg/dL over 48 hours, and 2) a >1.5x increase in serum creatinine from baseline within the first 30 days post-transplant.

Our cohort contained n=99 total patients, but after excluding 11 for incomplete data availability, n=88 patient records were analyzed. The odds ratios for experiencing AKI were calculated for patients with >3 days, 1-3 days, or no vancomycin exposure. Using the AKI definition of a serum creatinine increase by ≥0.3 mg/dL within 48 hours, patients with any vancomycin exposure had an OR of 5.21 (1.48-18.32) for experiencing AKI in the first 30 days post-HCT compared to patients with no vancomycin exposure at all. The odds of AKI were consistent across vancomycin exposure groups, such that patiets with 1-3 days of exposure had OR 5.68 (1.31-24.66) and patients with >3 days had OR 4.81 (1.13-20.49). These results were all consistent, yielding similar ORs, for the other definition of AKI. This finding suggests that any exposure, and not necessarily the duration of therapy, may be predictive of nephrotoxicity in the first 30 days post-HCT.

These acute toxicity events are important because cumulatively they may translate into long term renal impairment. Our cohort revealed that a marker of severely impaired renal function, an eGFR decrement of at least 50%, was seen in 3.4% of patients by day +100 and 9.1% of patients by day +365. This disappointingly high rate of profound renal compromise must be balanced by the real clinical need for vancomycin to treat susceptible bacterial infections in the first 30 days post-HCT, which was seen in 61% of patients the >3 days vancomycin exposure group. Yet these data do challenge the frequent assumption that short courses of vancomycin for “48 hour rule-outs” have a tolerable risk profile, and they underscore the need to rethink empiric antimicrobial strategies in transplant care.

Ongoing analyses of this cohort includes analyzing timing between vancomycin exposore and AKI events, as well as the contributory impact of concomitant nephrotoxin exposures such as chemotherapy, other medications, and IV contrast. Sub-analyses to look separately at allogeneic vs autologous transplant receipients are also underway.

This work highlights the need to quantify toxicities and side effects of therapies and paves the way for future efforts to minimize iatrogenic harm without compromising infection control.