Urinary proteomics in diabetes and CKD.

Steno Diabetes Center, Niels Steensens Vej 2, DK 2820 Gentofte, Denmark.
Journal of the American Society of Nephrology (Impact Factor: 9.47). 08/2008; 19(7):1283-90. DOI: 10.1681/ASN.2007091025
Source: PubMed

ABSTRACT Urinary biomarkers for diabetes, diabetic nephropathy, and nondiabetic proteinuric renal diseases were sought. For 305 individuals, biomarkers were defined and validated in blinded data sets using high-resolution capillary electrophoresis coupled with electrospray-ionization mass spectrometry. A panel of 40 biomarkers distinguished patients with diabetes from healthy individuals with 89% sensitivity and 91% specificity. Among patients with diabetes, 102 urinary biomarkers differed significantly between patients with normoalbuminuria and nephropathy, and a model that included 65 of these correctly identified diabetic nephropathy with 97% sensitivity and specificity. Furthermore, this panel of biomarkers identified patients who had microalbuminuria and diabetes and progressed toward overt diabetic nephropathy over 3 yr. Differentiation between diabetic nephropathy and other chronic renal diseases reached 81% sensitivity and 91% specificity. Many of the biomarkers were fragments of collagen type I, and quantities were reduced in patients with diabetes or diabetic nephropathy. In conclusion, this study shows that analysis of the urinary proteome may allow early detection of diabetic nephropathy and may provide prognostic information.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic nephropathy (DN) is the leading cause of end stage renal disease in the Western world. Microalbuminuria (MA) is the earliest and most commonly used clinical index of DN and is independently associated with cardiovascular risk in diabetic patients. Although MA remains an essential tool for risk stratification and monitoring disease progression in DN, a number of factors have called into question its predictive power. Originally thought to be predictive of future overt DN in 80% of patients, we now know that only around 30% of microalbuminuric patients progress to overt nephropathy after 10 years of follow up. In addition, advanced structural alterations in the glomerular basement membrane may already have occurred by the time MA is clinically detectable.Evidence in recent years suggests that a significant proportion of patients with MA can revert to normoalbuminuria and the concept of nonalbuminuric DN is well-documented, reflecting the fact that patients with diabetes can demonstrate a reduction in glomerular filtration rate without progressing from normo-to MA. There is an unmet clinical need to identify biomarkers with potential for earlier diagnosis and risk stratification in DN and recent developments in this field will be the focus of this review article.
    World journal of diabetes. 12/2014; 5(6):763-76.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mass spectrometry (MS) is currently the most promising tool for studying proteomics to investigate largescale proteins in a specific proteome. Emerging MS-based proteomics is widely applied to decipher complex proteome for discovering potential biomarkers. Given its growing usage in clinical medicine for biomarker discovery to predict, diagnose and confer prognosis, MS-based proteomics can benefit study of personalized medicine. In this review we introduce some fundamental MS theory and MS-based quantitative proteomic approaches as well as several representative clinical MS-based proteomics issues in Chest Medicine, Gerontology, and Nephrology.
    BioMedicine. 11/2014; 4:25.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypertension is a prevalent disorder in the world representing one of the major risk factors for heart attack and stroke. These risks are increased in salt sensitive individuals. Hypertension and salt sensitivity are complex phenotypes whose pathophysiology remains poorly understood and, remarkably, salt sensitivity is still laborious to diagnose. Here we present a urinary proteomic study specifically designed to identify urinary proteins relevant for the pathogenesis of hypertension and salt sensitivity. Despite previous studies that underlined the association of UMOD gene variants with hypertension, this work provides novel evidence showing different uromodulin protein level in the urine of hypertensive patients compared to healthy individuals. Notably, we also show that patients with higher level of uromodulin are homozygous for UMOD risk variant and display a decreased level of salt excretion, highlighting the essential role of UMOD in the regulation of salt reabsorption in hypertension. Additionally, we found that urinary nephrin 1, a marker of glomerular slit diaphragm, may predict a salt sensitive phenotype and positively correlate with increased albuminuria associated with this type of hypertension.
    BBA Clinical. 12/2014;


Available from
May 21, 2014