TY - JOUR
T1 - Intraglomerular Dysfunction Predicts Kidney Failure in Type 2 Diabetes
AU - Saulnier, Pierre J.
AU - Looker, Helen C.
AU - Mauer, Michael
AU - Najafian, Behzad
AU - Gand, Elise
AU - Ragot, Stephanie
AU - Nelson, Robert G.
AU - Bjornstad, Petter
N1 - Publisher Copyright:
© 2021 by the American Diabetes Association.
PY - 2021/10
Y1 - 2021/10
N2 - 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 resistance 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-to-RE ratio and PGLO with ESKD incidence in 237 Pima Indian individuals 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, and GFR 153 mL/min and median urine albumin–to–creatinine ratio 36 mg/g), 69 progressed to ESKD during a median follow-up of 17.5 years. In latent class analysis, distinct trajectories char-acterized by increasing RA-to-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 5 21%, P < 0.0001) and RA-to-RE ratio (R2 5 15%, P < 0.0001) also correlated with mesangial fractional volume, a structural predictor of DKD pro-gression. In conclusion, intraglomerular hemodynamic parameters associated strongly with incident ESKD and correlated with structural lesions of DKD.
AB - 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 resistance 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-to-RE ratio and PGLO with ESKD incidence in 237 Pima Indian individuals 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, and GFR 153 mL/min and median urine albumin–to–creatinine ratio 36 mg/g), 69 progressed to ESKD during a median follow-up of 17.5 years. In latent class analysis, distinct trajectories char-acterized by increasing RA-to-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 5 21%, P < 0.0001) and RA-to-RE ratio (R2 5 15%, P < 0.0001) also correlated with mesangial fractional volume, a structural predictor of DKD pro-gression. In conclusion, intraglomerular hemodynamic parameters associated strongly with incident ESKD and correlated with structural lesions of DKD.
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U2 - 10.2337/DB21-0154
DO - 10.2337/DB21-0154
M3 - Article
C2 - 34257069
AN - SCOPUS:85115295638
SN - 0012-1797
VL - 70
SP - 2344
EP - 2352
JO - Diabetes
JF - Diabetes
IS - 10
ER -