CHANGES IN KIDNEY FUNCTION AND RISK FACTORS FOR CHRONIC KIDNEY DISEASE IN CHILDHOOD CANCER SURVIVORS

Chronic kidney disease (CKD) as a late complication has become a problem since therapeutic advances have improved the life expectancy of patients with childhood cancer. While acute kidney injury (AKI) has been reported to be a risk factor for CKD, there have been few reports on how kidney function changes over time in childhood cancer survivors according to the presence or absence of AKI during treatment and CKD. This study aimed to evaluate the relationship between changes in the creatinine-based estimated glomerular filtration rate (Cr-eGFR) and the development of AKI and CKD in childhood cancer survivors.

From 2021 to 2023, among 175 patients with childhood cancer who visited the University of the Ryukyus Hospital, we identified 85 who had received their initial treatment after 2000 and had annual Cr-eGFR data available for 5 years post-treatment. We excluded two children with chromosomal or genetic abnormalities (one with trisomy 21 and another with Noonan syndrome), two children with no history of chemotherapy, and five children with a baseline eGFR (eGFR₀) <90 mL/min/1.73 m². These patients were classified into four groups on the basis of the presence or absence of AKI and CKD as follows: Group 1 (AKI–/CKD–), Group 2 (AKI+/CKD–), Group 3 (AKI–/CKD+), and Group 4 (AKI+/CKD+). CKD was diagnosed on the basis of a Cr-eGFR < 90 mL/min/1.73 m² at the final follow-up visit.

The 85 survivors had a median age of 6.4 years at initiating treatment, including 30 girls, and were studied for a median of 8.9 years. Forty-six patients developed AKI and 20 developed CKD. No patients required kidney replacement therapy. There were 31, 34, 8, and 12 patients in Groups 1 to 4, respectively. The Figure shows the 5-year changes in the mean Cr-eGFR in each group. Kaplan–Meier curves for the development of CKD were constructed for the four groups, and the Log-rank test revealed no significant differences between Groups 1 and 2, whereas a significant difference was observed between Groups 3 and 4. In contrast, in the univariate Cox proportional hazards model, AKI was not a significant risk factor for CKD (hazard ratios [HR] 1.455, 95% confidence interval [CI]: 0.594–3.564, p = 0.412). In a subanalysis, we evaluated eGFR₀, and ΔeGFR (eGFR₀ – eGFR₁, where eGFR₁ represents eGFR at 1 year after treatment) as potential early predictors of CKD using univariate Cox proportional hazards models. Both variables were significantly associated with CKD development, with HRs of 0.971 (95%CI: 0.946–0.994, p = 0.024) and 1.014 (95%CI: 1.0003–1.027, p = 0.046), respectively. The HRs indicate the relative risk of CKD for each 1-mL/min/1.73 m² increase in eGFR or ΔeGFR. In separate multivariate models that included AKI and each of these eGFR-related parameters, the associations remained significant and independent of AKI. Receiver operating characteristic curve analysis identified cutoff values of 110 and 20 mL/min/1.73 m², respectively, for predicting CKD. Patients were stratified according to these cutoff values (eGFR₀ ≤ 110 vs > 110, and ΔeGFR ≤ 20 vs > 20), and log-rank tests showed significant differences in CKD-free survival for both parameters (p = 0.015 and 0.001, respectively).

eGFR₀ ≤ 110 and ΔeGFR ≥ 20 mL/min/1.73 m² are risk factors for CKD, independent of AKI. Moreover, AKI was associated with accelerated CKD progression.