Association of Vancomycin Exposure with Short and Long Term Renal Function in a Contemporary Real-World Pediatric Stem Cell Transplant Cohort

Children undergoing Hematopoietic Cell Transplant (HCT) are at risk of renal injury from frequent exposures to nephrotoxic agents. The effect of nephrotoxins on renal function outcomes has not been well characterized in a contemporary real-world pediatric cohort. Our study focuses on one of the most commonly-used nephrotoxins, vancomycin, quantifying acute kidney injury (AKI) and long term renal function based on degrees of vancomycin exposure. We conducted a single center retrospective review of pediatric HCT recipients from 2018-2024. Clinical records including antimicrobial exposures and serial measures of serum creatinine were reviewed. Renal function was quantified via estimated glomerular filtration rate (eGFR) using the U25 CKiD calculator at baseline and at days +100 and +365 post-HCT (Fig 1). AKI was defined by KDIGO criteria as an increase in serum creatinine ≥0.3 mg/dL over 48 hours in the first 30 days post-transplant. The number of patients with eGFR <90mL/min/1.73m2 was quantified and is presented by eGFR range corresponding with CKD stage 2-5. We evaluated the change in eGFR from pre-HCT baseline and identified the number of patients who experienced eGFR decline of at least 50%. The ORs for experiencing AKI were calculated for patients with >3 days, 1-3 days, or no vancomycin exposure. Our cohort contained n=99 total patients, but after excluding 11 for incomplete data availability, n=88 patient records were analyzed. 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 (Fig 1). The odds of AKI were consistent across vancomycin exposure groups, such that patients 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). In our cohort, eGFR decrement of at least 50% was seen in 3.4% of patients by day +100 and 9.1% of patients by day +365 (Fig 1). Our finding that OR of AKI is consistent despite quantity of vancomycin exposure suggests that any exposure, and not necessarily the duration of therapy, is predictive of nephrotoxicity in the first 30 days post-HCT. Furthermore, our finding that nearly 10% of patients had profound long term GFR compromise is notable. These risks must be balanced by the clinical need for vancomycin to treat susceptible bacterial infections in the first 30 days post-HCT, which were seen in 61% of our patients who received >3 days of vancomycin. But importantly, these data challenge the frequent assumption that short courses of vancomycin for “48 hour rule-outs” have a tolerable risk profile, underscoring the need to rethink empiric antimicrobial strategies in transplant care. 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.