Renoprotective Effects and Timing of Evaluation of SGLT2 Inhibitors in Pediatric CKD

Introduction: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to have renoprotective effects regardless of the presence of diabetes mellitus. However, in children, the causative diseases of CKD differ from those in adults, and the efficacy of SGLT2 inhibitors in children has not been clearly established. Therefore, we report our experience with the renoprotective effects of SGLT2 inhibitors in pediatric CKD. Case Description: We analyzed 6 cases in which SGLT2 inhibitors were administered for more than 18 months. The underlying diseases were reflux nephropathy in 2 cases, renal hypoplasia in 2 cases, familial juvenile hyperuricemic nephropathy in 1 case, and Alport syndrome in 1 case. The median age at the start of administration was 16.0 years. The eGFR at the start of administration was 39.0 mL/min/1.73m2 (21.7-72.6), and the change in eGFR (ΔeGFR) over the 2 years prior to the start of administration was -3.37 mL/min/1.73m2/year (-9.66 to -2.18). Although the ΔeGFR worsened in 5 cases during the first 6 months after the start of administration, the ΔeGFR after 6 months was -1.82 mL/min/1.73m2/year (-2.95 to 2.02), showing improvement in all but 1 case. The median rate of change was 66.1% (-24.4 to 192.4%), and eGFR tended to increase in 2 cases. Adverse events included urinary tract infection in 1 case and mild hypoglycemia in 2 cases. Discussion: SGLT2 inhibitors are known to cause an initial decline in GFR, called the "initial drop," after the start of administration, making it difficult to determine the presence or absence of the initial drop from changes in ΔeGFR. Therefore, when we examined the ΔeGFR after 6 months of administration, which is presumed to be after the initial drop, improvement was observed in 5 out of 6 cases. Furthermore, SGLT2 inhibitors are reported to have a more rapid and significant renoprotective effect in patients with high proteinuria. However, in this study, the 5 cases in which ΔeGFR improved had non-glomerular congenital kidney and urinary tract diseases with negative or mild proteinuria. This study revealed that the ΔeGFR should be evaluated after a certain period from the start of administration to assess the renoprotective effect of SGLT2 inhibitors, and that sufficient renoprotective effects can be expected even in congenital kidney and urinary tract diseases with no or mild proteinuria.