Tubular Injury Biomarkers to Predict CKD and Hypertension at 3 Months Post-Cisplatin in Children.

Key Points: Tubular injury biomarkers are not individually strong predictors of 3-month post-cisplatin CKD. When combined with clinical measures, tubular injury biomarkers can predict post-therapy hypertension and identify high-risk patients.

Background: Urine kidney injury biomarkers measured during cisplatin therapy may identify patients at risk of adverse subsequent kidney outcomes. We examined relationships between tubular injury biomarkers collected early (early visit [EV]: first econd cisplatin cycle) and late (late visit: last second-last cisplatin cycle) during cisplatin therapy, with 3-month post-cisplatin CKD and hypertension (HTN).

Methods: We analyzed data from the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment Nephrotoxicity study, a 12-center prospective cohort study of 159 children receiving cisplatin. We measured urine neutrophil gelatinase-associated lipocalin (NGAL)/creatinine, kidney injury molecule-1/creatinine, tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP-7) (TIMP-2 and IGFBP-7 expressed as their product, ng/ml/1000) at an EV and late visit during cisplatin therapy with preinfusion, postinfusion, and hospital discharge sampling. Area under the curve (AUC) was calculated for biomarkers to detect 3-month post-cisplatin CKD (Kidney Disease Improving Global Outcomes guidelines: low eGFR or elevated urine albumin-to-creatinine ratio for age) and HTN (three BPs; per American Academy of Pediatrics guidelines).

Results: At median follow-up of 90 days, 52 of 118 patients (44%) and 17 of 125 patients (14%) developed CKD and HTN, respectively. Biomarker prediction for 3-month CKD was low to modest; NGAL combined with kidney injury molecule-1 at EV discharge yielded the highest AUC (0.67; 95% confidence interval, 0.57 to 0.77). Biomarker prediction of 3-month HTN was stronger, but modest; the highest AUC was from combining EV preinfusion NGAL and TIMP-2×IGFBP-7 (0.71; 95% confidence interval, 0.62 to 0.80). When EV preinfusion NGAL and TIMP-2×IGFBP-7 were added to the 3-month HTN clinical predictive model, AUCs increased from 0.81 (0.72 to 0.91) to 0.89 (0.83 to 0.95) ( < 0.05).

Conclusions: Tubular injury biomarkers we studied were individually not strong predictors of 3-month post-cisplatin kidney outcomes. Adding biomarkers to existing clinical prediction models may help predict post-therapy HTN and identify higher kidney-risk patients.