Structural predictors of loss of renal function in american indians with type 2 diabetes

Gudeta D. Fufaa, E. Jennifer Weil, Kevin V. Lemley, William C. Knowler, Frank C. Brosius, Berne Yee, Michael Mauer, Robert G. Nelson

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)254-261
Number of pages8
JournalClinical Journal of the American Society of Nephrology
Volume11
Issue number2
DOIs
StatePublished - Feb 5 2016

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North American Indians
Type 2 Diabetes Mellitus
Kidney
Confidence Intervals
Clinical Trials
Hemoglobins
Iothalamic Acid
Biopsy
Podocytes
Glomerular Basement Membrane
Losartan
Sclerosis
Research
Observational Studies
Renal Insufficiency
Albumins
Creatinine
Cell Count
Placebos

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

Fufaa, G. D., Weil, E. J., Lemley, K. V., Knowler, W. C., Brosius, F. C., Yee, B., ... Nelson, R. G. (2016). Structural predictors of loss of renal function in american indians with type 2 diabetes. Clinical Journal of the American Society of Nephrology, 11(2), 254-261. https://doi.org/10.2215/CJN.05760515

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 journalArticle

Fufaa, Gudeta D. ; Weil, E. Jennifer ; Lemley, Kevin V. ; Knowler, William C. ; Brosius, Frank C. ; Yee, Berne ; Mauer, Michael ; Nelson, Robert G. / Structural predictors of loss of renal function in american indians with type 2 diabetes. In: Clinical Journal of the American Society of Nephrology. 2016 ; Vol. 11, No. 2. pp. 254-261.
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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.",
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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

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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

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