Intraglomerular Dysfunction Predicts Kidney Failure in Type 2 Diabetes

No longitudinal data link intraglomerular hemodynamic dysfunction with end-stage kidney disease (ESKD) in people with type 2 diabetes (T2D). Afferent (R_A) and efferent (R_E) arteriolar tone and intraglomerular pressure (P_GLO) are not directly measurable in humans but are estimable from glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure, hematocrit, and plasma oncotic pressure. We examined the association of the R_A/R_E ratio and P_GLO with ESKD incidence in 237 Pima Indian persons with T2D who underwent serial measures of GFR (iothalamate) and RPF (p-aminohippurate). Their association with kidney structural lesions was also examined in a subset of 111 participants. Of the 237 participants (mean age 42 years, diabetes duration 11 years, GFR 153 ml/min, median ACR 36 mg/g), 69 progressed to ESKD during median follow-up of 17.5 years. In latent class analysis, distinct trajectories characterized by increasing R_A/R_E ratio (HR: 4.60, 95% CI 2.55-8.31) or elevated P_GLO followed by a rapid decline (HR: 2.96, 95% CI 1.45-6.02) strongly predicted incident ESKD. P_GLO (R²=21%, p<0.0001) and R_A/R_E (R²=15%, p<0.0001) also correlated with mesangial fractional volume, a structural predictor of DKD progression. In conclusion, intraglomerular hemodynamic parameters associated strongly with incident ESKD and correlated with structural lesions of DKD.