Prediction of diabetic nephropathy using urine proteomic profiling 10 years prior to development of nephropathy

Hasan H. Otu, Handan Can, Dimitrios Spentzos, Robert G. Nelson, Robert L. Hanson, Helen C. Looker, William C. Knowler, Manuel Monroy, Towia A. Libermann, S. Ananth Karumanchi, Ravi Thadhani

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - We examined whether proteomic technologies identify novel urine proteins associated with subsequent development of diabetic nephropathy in subjects with type 2 diabetes before evidence of microalbuminuria. RESEACH DESIGN AND METHODS - In a nested case-control study of Pima Indians with type 2 diabetes, baseline (serum creatinine <1.2 mg/dl and urine albumin excretion <30 mg/g) and 10-year urine samples were examined. Case subjects (n = 31) developed diabetic nephropathy (urinary albumin-to-creatinine ratio >300 mg/g) over 10 years. Control subjects (n = 31) were matched to case subjects (1:1) according to diabetes duration, age, sex, and BMI but remained normoalbuminuric (albumin-to-creatinine ratio <30 mg/g) over the same 10 years. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on baseline urine samples, and training (14 cases:14 controls) and validation (17:17) sets were tested. RESULTS - At baseline, A1C levels differed between case and control subjects. SELDI-TOF MS detected 714 unique urine protein peaks. Of these, a 12-peak proteomic signature correctly predicted 89% of cases of diabetic nepropathy (93% sensitivity, 86% specificity) in the training set. Applying this same signature to the independent validation set yielded an accuracy rate of 74% (71% sensitivity, 76% specificity). In multivariate analyses, the 12-peak signature was independently associated with subsequent diabetic nephropathy when applied to the validation set (odds ratio [OR] 7.9 [95% CI 1.5-43.5], P = 0.017) and the entire dataset (14.5 [3.7-55.6], P = 0.001), and A1C levels were no longer significant. CONCLUSIONS - Urine proteomic profiling identifies normoalbuminuric subjects with type 2 diabetes who subsequently develop diabetic nephropathy. Further studies are needed to characterize the specific proteins involved in this early prediction.

Original languageEnglish (US)
Pages (from-to)638-643
Number of pages6
JournalDiabetes Care
Volume30
Issue number3
DOIs
StatePublished - Mar 1 2007

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Diabetic Nephropathies
Proteomics
Urine
Type 2 Diabetes Mellitus
Mass Spectrometry
Creatinine
Lasers
Potassium Iodide
Sensitivity and Specificity
Proteins
Case-Control Studies
Albumins
Multivariate Analysis
Odds Ratio
Technology
Serum

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Otu, H. H., Can, H., Spentzos, D., Nelson, R. G., Hanson, R. L., Looker, H. C., ... Thadhani, R. (2007). Prediction of diabetic nephropathy using urine proteomic profiling 10 years prior to development of nephropathy. Diabetes Care, 30(3), 638-643. https://doi.org/10.2337/dc06-1656

Prediction of diabetic nephropathy using urine proteomic profiling 10 years prior to development of nephropathy. / Otu, Hasan H.; Can, Handan; Spentzos, Dimitrios; Nelson, Robert G.; Hanson, Robert L.; Looker, Helen C.; Knowler, William C.; Monroy, Manuel; Libermann, Towia A.; Karumanchi, S. Ananth; Thadhani, Ravi.

In: Diabetes Care, Vol. 30, No. 3, 01.03.2007, p. 638-643.

Research output: Contribution to journalArticle

Otu, HH, Can, H, Spentzos, D, Nelson, RG, Hanson, RL, Looker, HC, Knowler, WC, Monroy, M, Libermann, TA, Karumanchi, SA & Thadhani, R 2007, 'Prediction of diabetic nephropathy using urine proteomic profiling 10 years prior to development of nephropathy', Diabetes Care, vol. 30, no. 3, pp. 638-643. https://doi.org/10.2337/dc06-1656
Otu, Hasan H. ; Can, Handan ; Spentzos, Dimitrios ; Nelson, Robert G. ; Hanson, Robert L. ; Looker, Helen C. ; Knowler, William C. ; Monroy, Manuel ; Libermann, Towia A. ; Karumanchi, S. Ananth ; Thadhani, Ravi. / Prediction of diabetic nephropathy using urine proteomic profiling 10 years prior to development of nephropathy. In: Diabetes Care. 2007 ; Vol. 30, No. 3. pp. 638-643.
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AU - Otu, Hasan H.

AU - Can, Handan

AU - Spentzos, Dimitrios

AU - Nelson, Robert G.

AU - Hanson, Robert L.

AU - Looker, Helen C.

AU - Knowler, William C.

AU - Monroy, Manuel

AU - Libermann, Towia A.

AU - Karumanchi, S. Ananth

AU - Thadhani, Ravi

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N2 - OBJECTIVE - We examined whether proteomic technologies identify novel urine proteins associated with subsequent development of diabetic nephropathy in subjects with type 2 diabetes before evidence of microalbuminuria. RESEACH DESIGN AND METHODS - In a nested case-control study of Pima Indians with type 2 diabetes, baseline (serum creatinine <1.2 mg/dl and urine albumin excretion <30 mg/g) and 10-year urine samples were examined. Case subjects (n = 31) developed diabetic nephropathy (urinary albumin-to-creatinine ratio >300 mg/g) over 10 years. Control subjects (n = 31) were matched to case subjects (1:1) according to diabetes duration, age, sex, and BMI but remained normoalbuminuric (albumin-to-creatinine ratio <30 mg/g) over the same 10 years. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on baseline urine samples, and training (14 cases:14 controls) and validation (17:17) sets were tested. RESULTS - At baseline, A1C levels differed between case and control subjects. SELDI-TOF MS detected 714 unique urine protein peaks. Of these, a 12-peak proteomic signature correctly predicted 89% of cases of diabetic nepropathy (93% sensitivity, 86% specificity) in the training set. Applying this same signature to the independent validation set yielded an accuracy rate of 74% (71% sensitivity, 76% specificity). In multivariate analyses, the 12-peak signature was independently associated with subsequent diabetic nephropathy when applied to the validation set (odds ratio [OR] 7.9 [95% CI 1.5-43.5], P = 0.017) and the entire dataset (14.5 [3.7-55.6], P = 0.001), and A1C levels were no longer significant. CONCLUSIONS - Urine proteomic profiling identifies normoalbuminuric subjects with type 2 diabetes who subsequently develop diabetic nephropathy. Further studies are needed to characterize the specific proteins involved in this early prediction.

AB - OBJECTIVE - We examined whether proteomic technologies identify novel urine proteins associated with subsequent development of diabetic nephropathy in subjects with type 2 diabetes before evidence of microalbuminuria. RESEACH DESIGN AND METHODS - In a nested case-control study of Pima Indians with type 2 diabetes, baseline (serum creatinine <1.2 mg/dl and urine albumin excretion <30 mg/g) and 10-year urine samples were examined. Case subjects (n = 31) developed diabetic nephropathy (urinary albumin-to-creatinine ratio >300 mg/g) over 10 years. Control subjects (n = 31) were matched to case subjects (1:1) according to diabetes duration, age, sex, and BMI but remained normoalbuminuric (albumin-to-creatinine ratio <30 mg/g) over the same 10 years. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on baseline urine samples, and training (14 cases:14 controls) and validation (17:17) sets were tested. RESULTS - At baseline, A1C levels differed between case and control subjects. SELDI-TOF MS detected 714 unique urine protein peaks. Of these, a 12-peak proteomic signature correctly predicted 89% of cases of diabetic nepropathy (93% sensitivity, 86% specificity) in the training set. Applying this same signature to the independent validation set yielded an accuracy rate of 74% (71% sensitivity, 76% specificity). In multivariate analyses, the 12-peak signature was independently associated with subsequent diabetic nephropathy when applied to the validation set (odds ratio [OR] 7.9 [95% CI 1.5-43.5], P = 0.017) and the entire dataset (14.5 [3.7-55.6], P = 0.001), and A1C levels were no longer significant. CONCLUSIONS - Urine proteomic profiling identifies normoalbuminuric subjects with type 2 diabetes who subsequently develop diabetic nephropathy. Further studies are needed to characterize the specific proteins involved in this early prediction.

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