ESPE Yearbook of Paediatric Endocrinology

Brief Summary: The authors performed exploratory analyses to identify distinct eGFR trajectories associated with risk of albuminuria in 377 adolescents with T2D. The findings underscore the importance of annual GFR assessments in young people with T2D.

Comment: Diabetic kidney disease (DKD) is the primary microvascular complication in adolescents with T2D, and is a leading cause of morbidity and mortality. Albuminuria is the earliest clinical indicator of DKD. Data from adults with T2D indicate that the natural history of DKD often begins with hyperfiltration—an elevated glomerular filtration rate (GFR) exceeding 120 mL/min/1.73 m²—due to obesity and impaired glucose tolerance. This hyperfiltration stage predicts kidney function decline even before other clinical signs emerge. The second stage in the progression of kidney dysfunction, still asymptomatic, involves a mild reduction in GFR (60-89 mL/min/1.73 m²). During this phase, structural changes in the kidney are common but often reversible, highlighting a crucial window for risk factor modification.

The understanding of early DKD progression in adolescents with youth-onset T2D is still limited. This study delineated distinct hyperfiltration trajectories and their association with albuminuria in youth-onset T2D, with a follow-up duration of at least 10 years. GFR trajectories and eGFR peaks were analyzed to more accurately capture glomerular hyperfiltration patterns. It included 377 adolescents (63%) with T2D. At baseline, the median age was 14 years, the median diabetes duration was 6 months, the mean BMI was 34.9 kg/m², the mean HbA1c was 6.0%, and the mean eGFR was 120 mL/min/1.73 m².

Five distinct eGFR trajectories were identified. The first 3 groups showed relatively stable eGFR levels, differing mainly in their baseline eGFR values of 108, 118, and 131 mL/min/1.73 m², respectively. The fourth group began with a baseline eGFR of 141 mL/min/1.73 m², which increased to 176 mL/min/1.73 m² by year 10. In contrast, the fifth group showed a progressive decline in eGFR, dropping below 60 mL/min/1.73 m² by the end of the study. There were no major differences in stratification of eGFR when data was restricted to those with albuminuria (n=150).

These data suggest that in young people with T2D, a continuous and increasing filtration rate might be a warning sign of DKD. However, we need more time to see if this increased filtration will eventually lead to a decline in kidney function. Notably, the group with progressively increasing eGFR, which showed the highest peak eGFR and albuminuria levels, tended to be female. This contrasts with observations in adult-onset T2D, where males typically have higher risk of albuminuric DKD. Patients who showed the greatest peak hyperfiltration also showed the highest degree of albuminuria both at baseline and after 10 years of follow-up. The median time to peak eGFR in this group was 8 years.