Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients.

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66-0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66-0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = -0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.

Long-term complications of acute kidney injury in children.

PURPOSE OF REVIEW: The current review will describe the current evidence and mechanisms of acute kidney injury (AKI) as a risk factor for long-term kidney complications, summarize the rationale for AKI follow-up and present an approach to monitoring children with AKI. Despite emerging evidence linking AKI with risk for long-term kidney and cardiovascular outcomes, many children who develop AKI are not followed for kidney disease development after hospital discharge. Better understanding of long-term complications after AKI and practical algorithms for follow-up will hopefully increase the rate and quality of post-AKI monitoring. RECENT FINDINGS: Recent evidence shows that pediatric AKI is associated with long-term renal outcomes such as chronic kidney disease (CKD) and hypertension, both known to increase cardiovascular risk. The mechanism of AKI progression to CKD involves maladaptive regeneration of tubular epithelial and endothelial cells, inflammation, fibrosis and glomerulosclerosis. Many AKI survivors are not followed, and no guidelines for pediatric AKI follow-up have been published. SUMMARY: Children who had AKI are at increased risk of long-term renal complications but many of them are not monitored for these complications. Recognizing long-term outcomes post-AKI and integration of follow-up programs may have a long-lasting positive impact on patient health.