Abstract
Background and objectives Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Design, setting, participants, & measurements Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Results Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13–158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1–9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Conclusions Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 254-261 |
| Number of pages | 8 |
| Journal | Clinical Journal of the American Society of Nephrology |
| Volume | 11 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 5 2016 |
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Keywords
- Diabetes mellitus, type 2
- Diabetic nephropathy
- Epidemiology and outcomes
- Glomerular filtration rate
- Humans
- Indians, North American
- Kidney biopsy
- Kidney diseases
- Renal morphology
Cite this
Structural predictors of loss of renal function in american indians with type 2 diabetes. / Fufaa, Gudeta D.; Weil, E. Jennifer; Lemley, Kevin V.; Knowler, William C.; Brosius, Frank C.; Yee, Berne; Mauer, Michael; Nelson, Robert G.
In: Clinical Journal of the American Society of Nephrology, Vol. 11, No. 2, 05.02.2016, p. 254-261.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural predictors of loss of renal function in american indians with type 2 diabetes
AU - Fufaa, Gudeta D.
AU - Weil, E. Jennifer
AU - Lemley, Kevin V.
AU - Knowler, William C.
AU - Brosius, Frank C.
AU - Yee, Berne
AU - Mauer, Michael
AU - Nelson, Robert G.
PY - 2016/2/5
Y1 - 2016/2/5
N2 - Background and objectives Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Design, setting, participants, & measurements Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Results Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13–158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1–9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Conclusions Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes.
AB - Background and objectives Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Design, setting, participants, & measurements Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Results Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13–158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1–9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Conclusions Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes.
KW - Diabetes mellitus, type 2
KW - Diabetic nephropathy
KW - Epidemiology and outcomes
KW - Glomerular filtration rate
KW - Humans
KW - Indians, North American
KW - Kidney biopsy
KW - Kidney diseases
KW - Renal morphology
UR - http://www.scopus.com/inward/record.url?scp=84957061000&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957061000&partnerID=8YFLogxK
U2 - 10.2215/CJN.05760515
DO - 10.2215/CJN.05760515
M3 - Article
C2 - 26792530
AN - SCOPUS:84957061000
VL - 11
SP - 254
EP - 261
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
SN - 1555-9041
IS - 2
ER -