Diabetic kidney disease (DKD) remains one of the leading causes of reduced lifespan in diabetes. The quest for both prognostic and surrogate endpoint biomarkers for advanced DKD and end-stage renal disease has received major investment and interest in recent years. However, at present no novel biomarkers are in routine use in the clinic or in trials. This review focuses on the current status of prognostic biomarkers. First, we emphasise that albuminuria and eGFR, with other routine clinical data, show at least modest prediction of future renal status if properly used. Indeed, a major limitation of many current biomarker studies is that they do not properly evaluate the marginal increase in prediction on top of these routinely available clinical data. Second, we emphasise that many of the candidate biomarkers for which there are numerous sporadic reports in the literature are tightly correlated with each other. Despite this, few studies have attempted to evaluate a wide range of biomarkers simultaneously to define the most useful among these correlated biomarkers. We also review the potential of high-dimensional panels of lipids, metabolites and proteins to advance the field, and point to some of the analytical and post-analytical challenges of taking initial studies using these and candidate approaches through to actual clinical biomarker use.
The use of an ACE inhibitor and a statin did not change the albumin-to-creatinine ratio over time. (Funded by the Juvenile Diabetes Research Foundation and others; AdDIT ClinicalTrials.gov number, NCT01581476 .).
Design: In order to characterize whether different degrees of adipose tissue storage may be associated with markers of early atherosclerosis, we evaluated oxidant-antioxidant status and inflammatory markers and determined carotid intima-media thickness (cIMT) in healthy constitutional lean and obese pre-pubertal children. Methods: Eighty healthy pre-pubertal lean and obese children were recruited and compared with 40 age, gender, and pubertal stage-matched normal controls. Anthropometric measurements, oxidant (urinary isoprostanes (PGF-2a), lag phase, and malondialdehyde (MDA)) and antioxidant status (vitamin E), inflammatory markers (high sensitive C-reactive protein (hs-CRP)), and insulin sensitivity (fasting glucose-insulin ratio, homeostasis model assessment of insulin resistance (HOMA-IR)) were investigated. Furthermore, cIMT was measured by high-resolution ultrasound. Results: hs-CRP was not different between lean and control subjects (PZ0.45), while higher values were found in obese compared with lean and control children (P!0.001 and P!0.001 respectively). PGF-2a and MDA were higher while lag phase shorter in lean and obese subjects compared with controls (lean P!0.001; P!0.001; P!0.001 and obese P!0.001; P!0.001; P!0.001 respectively), while no differences were documented between lean and obese subjects (PZ0.78, PZ0.019, and PZ0.53 respectively). Compared with controls, cIMT was increased in lean and in obese subjects (PZ0.001; PZ0.004), while no differences were documented between obese and lean subjects (PZ0.1). In a multiple stepwise linear regression analysis, cIMT was related with PGF-2a (bZ0.641, P!0.001) and HOMA-IR (bZ0.307; P!0.001). Conclusions: Pre-pubertal lean and obese children present increased oxidative stress and impaired inflammation and insulin sensitivity, which in turn seem to result in similar impaired endothelial dysfunction and early signs of atherosclerosis, already in childhood.
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