Urinary collagen IV and πGST: potential biomarkers for detecting localized kidney injury in diabetes--a pilot study.
ABSTRACT Urinary biomarkers can identify damage to specific parts of the nephron. We performed a cross-sectional study to characterise the pattern of diabetic nephropathy using urinary biomarkers of glomerular fibrosis (collagen IV), proximal tubular damage (α-glutathione-S-transferase, GST) and distal tubular damage (πGST).
Clinical data from 457 unselected patients attending a hospital diabetes clinic were collected. Spot urine samples were analysed for albumin and creatinine. Biomarkers were measured by enzyme-linked immunosorbent assay, and corrected to urinary creatinine.
All 3 biomarkers correlated weakly with albumin/creatinine ratios (Pearson correlation <0.2, p values <0.001). The most common abnormality was elevated urinary collagen IV (glomerular, 35%) compared to αGST (proximal tubule, 18%) or πGST (distal tubule, 15%). The proportion of patients with abnormal biomarker results increased across the normo-, micro- and macroalbuminuria groups, with collagen IV (26, 58, 65%) and πGST (11, 25, 35%) but not αGST.
In patients with diabetes, these urinary biomarkers appear to identify renal damage that is related to, but distinct from, urine albumin/creatinine ratios. The markers of glomerular fibrosis and distal tubular damage related most closely to the degree of albuminuria. Longitudinal studies are now required to assess whether these biomarkers can detect early renal disease with greater specificity and sensitivity than the albumin/creatinine ratio.
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ABSTRACT: PURPOSE OF REVIEW: A focused review of the nature, source, physiological role and rapidly expanding evidence for glutathione S-transferase (GST) subtypes π and α as biomarkers of acute kidney injury (AKI) in patients undergoing cardiac surgery. Expanded insights into the site-specific expression of the GSTs in defined parts of the nephron during renal damage are presented, with particular emphasis on the pathogenesis of cardiac surgery and cardiopulmonary bypass (CPB)-associated AKI and the role of GSTs in oxygen radical disposal. RECENT FINDINGS: Recent developments have highlighted a potential role of urinary α-GST and π-GST in the diagnostic evaluation of cardiac surgery-associated AKI. Both urinary α-GST and π-GST are detected in the postoperative period. π-GST performed best at predicting AKI severity at the time of the initial diagnosis of AKI. α-GST was able to predict the future development of both stage 1 and stage 3 AKI. SUMMARY: The current data from a small number of patients suggest a potential role of urinary GSTs in the clinical diagnostic evaluation of AKI following cardiac surgery. The performance of the GSTs for the early diagnosis of AKI needs to be validated in larger multicentre studies and in other patient populations at increased risk of AKI (e.g. patients with acute transplant rejection, septic patients). Comparison with other emerging AKI biomarkers is required to continue the development of π-GST and α-GST. Finally, additional studies examining the pathophysiological role of the GSTs in minimizing oxygen free radical exposure in the renal tubules during CPB may shed further light into their role as promising biomarkers of cardiac surgery-associated AKI.Current opinion in critical care 10/2010; 16(6). DOI:10.1097/MCC.0b013e32833fdd9a · 3.18 Impact Factor
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ABSTRACT: Both type 1 and type 2 diabetes are associated with severe complications including diabetic nephropathy. With the rapidly rising number of patients with diabetes worldwide, diabetic nephropathy is becoming one of the most common causes of renal disease. Much research effort is being put into how to identify diabetic nephropathy in patients with diabetes. A considerable number of biomarker studies were recently published on markers in plasma or urine, either with the aim to distinguish patients with or without diabetic nephropathy, or with the aim to predict renal outcome in those patients with diabetic nephropathy. We review the most recent findings on this subject and discuss the lack of histologically proven diabetic nephropathy in the majority of these studies. Most conspicuous in the field of diabetic nephropathy was the recent identification of a number of biomarkers used either in the diagnosis of diabetic nephropathy or in the evaluation of therapies meant to prevent, slow down, or reverse the processes causing diabetic nephropathy. For the histopathology of diabetic nephropathy, a new classification system was launched in 2010, which will be discussed together with future perspectives. Combining histopathological grading of and biomarkers for diabetic nephropathy will further our understanding of this complex disease manifestation.Current opinion in nephrology and hypertension 03/2011; 20(3):285-9. DOI:10.1097/MNH.0b013e328345bc1c · 3.96 Impact Factor
Chapter: Post-Inflammatory NephropathyUrinary Tract Infections, 09/2011; , ISBN: 978-953-307-757-4