Advanced glycation end products predict loss of renal function and correlate with lesions of diabetic kidney disease in American indians with type 2 diabetes

Pierre Jean Saulnier, Kevin M. Wheelock, Scott Howell, E. Jennifer Weil, Stephanie K. Tanamas, William C. Knowler, Kevin V. Lemley, Michael Mauer, Berne Yee, Robert G. Nelson, Paul J. Beisswenger

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Abstract

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ‡40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA1c 9.2%, GFR 164 mL/min, and albumin-To-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08-2.37]) ormethylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02-1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = 20.26, P = 0.01; and partial r = 20.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates.

Original languageEnglish (US)
Pages (from-to)3744-3753
Number of pages10
JournalDiabetes
Volume65
Issue number12
DOIs
StatePublished - Dec 1 2016

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Advanced Glycosylation End Products
North American Indians
Diabetic Nephropathies
Type 2 Diabetes Mellitus
Kidney
Glomerular Filtration Rate
Pyruvaldehyde
Lysine
Biopsy
Losartan
Albumins
Creatinine
Observation
Clinical Trials
imidazolone
Serum

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Saulnier, P. J., Wheelock, K. M., Howell, S., Weil, E. J., Tanamas, S. K., Knowler, W. C., ... Beisswenger, P. J. (2016). Advanced glycation end products predict loss of renal function and correlate with lesions of diabetic kidney disease in American indians with type 2 diabetes. Diabetes, 65(12), 3744-3753. https://doi.org/10.2337/db16-0310

Advanced glycation end products predict loss of renal function and correlate with lesions of diabetic kidney disease in American indians with type 2 diabetes. / Saulnier, Pierre Jean; Wheelock, Kevin M.; Howell, Scott; Weil, E. Jennifer; Tanamas, Stephanie K.; Knowler, William C.; Lemley, Kevin V.; Mauer, Michael; Yee, Berne; Nelson, Robert G.; Beisswenger, Paul J.

In: Diabetes, Vol. 65, No. 12, 01.12.2016, p. 3744-3753.

Research output: Contribution to journalArticle

Saulnier, PJ, Wheelock, KM, Howell, S, Weil, EJ, Tanamas, SK, Knowler, WC, Lemley, KV, Mauer, M, Yee, B, Nelson, RG & Beisswenger, PJ 2016, 'Advanced glycation end products predict loss of renal function and correlate with lesions of diabetic kidney disease in American indians with type 2 diabetes' Diabetes, vol. 65, no. 12, pp. 3744-3753. https://doi.org/10.2337/db16-0310
Saulnier, Pierre Jean ; Wheelock, Kevin M. ; Howell, Scott ; Weil, E. Jennifer ; Tanamas, Stephanie K. ; Knowler, William C. ; Lemley, Kevin V. ; Mauer, Michael ; Yee, Berne ; Nelson, Robert G. ; Beisswenger, Paul J. / Advanced glycation end products predict loss of renal function and correlate with lesions of diabetic kidney disease in American indians with type 2 diabetes. In: Diabetes. 2016 ; Vol. 65, No. 12. pp. 3744-3753.
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