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Intraglomerular Dysfunction Predicts Kidney Failure in Type 2 Diabetes

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posted on 13.07.2021, 14:11 by Pierre J Saulnier, Helen C Looker, Michael Mauer, Behzad Najafian, Elise Gand, Stephanie Ragot, Robert G Nelson, Petter Bjornstad
No longitudinal data link intraglomerular hemodynamic dysfunction with end-stage kidney disease (ESKD) in people with type 2 diabetes (T2D). Afferent (RA) and efferent (RE) arteriolar tone and intraglomerular pressure (PGLO) 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 RA/RE ratio and PGLO 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 RA/RE ratio (HR: 4.60, 95% CI 2.55-8.31) or elevated PGLO followed by a rapid decline (HR: 2.96, 95% CI 1.45-6.02) strongly predicted incident ESKD. PGLO (R2=21%, p<0.0001) and RA/RE (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.

Funding

Financial support for this work provided by the American Diabetes Association (Clinical Science Award 1-08-CR-42) and by the Intramural Research Program of the NIDDK. P.B. receives salary and research support from NIDDK (DK116720, DK114886), JDRF (2-SRA-2019-845-S-B, 3-SRA-2017-424-M-B), Boettcher Foundation, Center for Women’s Health Research at University of Colorado, the Department of Pediatrics, Section of Endocrinology and Barbara Davis Center for Diabetes at University of Colorado School of Medicine.

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