Kidney Injury in Children after Hematopoietic Stem Cell Transplant

**Background:** Hematopoietic cell transplant (HCT) is a life-saving therapy for many malignant and non-malignant pediatric diseases but is associated with serious complications, including acute kidney injury (AKI). AKI occurs in 21–84% of pediatric HCT patients and contributes significantly to morbidity and mortality. The etiology is often multifactorial, involving kidney hypoperfusion, nephrotoxicity from immunosuppressive and antimicrobial agents, and transplant-specific complications such as transplant-associated thrombotic microangiopathy (TA-TMA) and sinusoidal obstruction syndrome (SOS).

**Methods:** This is a narrative review summarizing the current literature on AKI in children after HCT. The authors synthesize findings from multiple cohort studies, meta-analyses, and clinical trials to describe the incidence, risk factors, diagnostic criteria, associated conditions, management strategies, and long-term outcomes of AKI in this population.

**Key Results:** The reported incidence of AKI after pediatric HCT ranges from 21% to 84%, varying partly due to non-standardized definitions. In a meta-analysis of 571 children, AKI developed in 124 (21.7%) within the first 100 days post-transplant, with a median onset of 4–6 weeks. Risk factors include myeloablative conditioning (45.7% incidence vs. 17.1% with reduced intensity conditioning), acute graft versus host disease (GVHD), and SOS. TA-TMA occurs in 16% of children (median onset 47 days post-transplant); among 98 children with TA-TMA, AKI developed in 66%, 15% required renal replacement therapy, and overall survival was significantly lower (78% vs. 93%, p=0.001). Proteinuria was present in 80% of children with TA-TMA and was associated with higher 6-month mortality (27% vs. 5%, p=0.04). Eculizumab improved 1-year survival in high-risk TA-TMA to 66% vs. 16.7% in untreated historical controls. SOS occurs in 20–60% of patients and is associated with high mortality; defibrotide reduces mortality and reverses organ dysfunction. Fluid overload (FO) >10% is common and associated with worse outcomes; each 1% increase in FO increases odds of mortality by 6%. In mechanically ventilated pediatric HCT patients, each 1% increase in cumulative fluid balance on day 3 was associated with a 3% increase in ICU mortality (adjusted OR 1.03; 95% CI 1.00–1.07). CKRT is required in nearly one-third of patients with AKI; ICU mortality in children post HCT requiring CKRT is 52–65%, and 1-year overall survival is 27.4% (95% CI 16–40.5%, p<0.0001). Biomarkers such as NGAL can detect AKI up to 48 hours before serum creatinine rises. CKD develops in up to 48% of pediatric HCT survivors, with incidence 10-fold higher than the healthy population. Albuminuria at day 100 was associated with CKD at 1 year (OR 4.0; 95% CI 1.1–14.6), and proteinuria at day 100 conveyed a six-fold increase in risk of non-relapse mortality by 1 year.

**Clinical Implications:** Early recognition of AKI using standardized KDIGO criteria and novel biomarkers (NGAL, cystatin C, KIM-1) is crucial for timely intervention. Management should focus on identifying etiology, preventing hypoperfusion, adjusting nephrotoxic medications, and preventing fluid overload. CKRT should be considered when FO exceeds 10% and diuretics fail. Regional citrate anticoagulation is preferred over heparin for CKRT due to lower bleeding complications (5.1% vs. 16.9%) and longer filter lifespan (47 h vs. 26 h). Long-term follow-up is essential, including monitoring of GFR, microalbuminuria, and blood pressure. ACE inhibitors or ARBs are recommended for hypertension and proteinuria. A multidisciplinary approach involving nephrology is recommended for children with any degree of CKD post HCT.