Article

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

Harvard University, Cambridge, Massachusetts, United States
Diabetes care (Impact Factor: 8.57). 03/2007; 30(3):638-43. DOI: 10.2337/dc06-1656
Source: PubMed

ABSTRACT 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.
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.
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 nephropathy (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.
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.

0 Followers
 · 
172 Views
  • Source
    Nephrology Dialysis Transplantation 12/2014; 30(2). DOI:10.1093/ndt/gfu372 · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the current era of large-scale biology, proteomics has evolved as a powerful, new technique that aims to identify, quantify, and analyze a large number of proteins in a functional context. Therefore, proteomics can be used to study cellular pathways and identify disease biomarkers. In this review, we first outline the principles of two important proteomics techniques that either use difference gel electrophoresis (DIGE) or liquid chromatography (LC) for protein separation, followed by tandem mass spectrometry (MS/MS). The advantages and limitations of each technique are discussed, emphasizing the ability of DIGE to perform quantitative proteomics and the high-throughput and high-sensitivity characteristics of LC-MS/MS. We have employed both techniques to unravel the molecular machinery of vasopressin signaling, which governs water homeostasis by recruiting aquaporin-2 (AQP2) water channels after activation of the vasopressin-2 receptor by vasopressin. Several aspects of vasopressin signaling in the inner medullary collecting duct (IMCD) were investigated, including the short- and long-term regulation of AQP2, phosphoproteomics, signaling during vasopressin escape, and the proteomes of AQP2-bearing vesicles and the IMCD plasma membranes. We also emphasize that proteomics of body fluids will be the strategy to identify disease biomarkers, and therefore conclude the review by highlighting the perspectives of biomarker discovery in urinary exosomes.
    Contributions to nephrology 02/2008; 160:172-85. DOI:10.1159/000125981 · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An important issue in congenital unilateral ureteropelvic junction (UPJ) obstruction, a frequent pathology in newborns, is whether infants should undergo surgery. Non-invasive biomarkers to reduce or replace the current invasive clinical exploration are not available. The objective of this study was to identify urinary markers of UPJ obstruction. We compared a number of proteome technologies to study the urinary proteome in UPJ obstruction and selected online capillary electrophoresis coupled to mass-spectrometry for the selection of non-invasive prognostic biomarkers. We selected 53 urinary biomarkers that were able to distinguish between different levels of UPJ obstruction. In a prospective study using these 53 biomarkers, we predicted with 97% accuracy, and several months in advance, the clinical outcome of 36 UPJ-obstruction patients. Some of the discriminating biomarkers were identified. A newly identified marker, proSAAS (proprotein convertase subtilisin/kexin type 1 inhibitor), generated a new hypothesis in the physiopathology of UPJ obstruction. These results show that analysis of urinary polypeptides in newborns with UPJ obstruction can predict their clinical outcome.
    Contributions to nephrology 02/2008; 160:127-41. DOI:10.1159/000125956 · 1.53 Impact Factor