Progression of diabetic nephropathy in normotensive type 1 diabetic patients

Progression of diabetic nephropathy in normotensive type 1 diabetic patientsBackgroundThe first aim of our long-term study was to describe the natural history of diabetic nephropathy in 59 normotensive type 1 diabetic patients. Secondly, we evaluated genetic and nongenetic progression promoters.MethodsThe following progression promoters were determined: the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene, blood pressure, albuminuria, hemoglobin A1c, cholesterol, smoking, height, and gender. We studied the natural history by measuring 51Cr-EDTA plasma clearance at yearly intervals at least three times during [median (range)] 5.5 (2.2 to 18.3) years.ResultsAt baseline the three groups (II, N = 11; ID, N = 25, and DD, N = 23) had comparable GFR (103 ± 16; 99 ± 19; 113 ± 22 ml/min/1.73 m2, respectively; mean ± SD), arterial blood pressure, albuminuria, and hemoglobin A1c. During the follow-up there was a median rate of decline in GFR in all 59 patients of 1.2 (range 12.9 to –4.4) ml/min/year. During the study period no significant differences were observed in: the rate of decline in glomerular filtration rate [median (range) 0.9 (10.6 to –1.9); 2.5 (12.9 to –4.4); 1.4 (10.8 to –1.9 ml/min/year)], arterial blood pressure, albuminuria, hemoglobin A1c or cholesterol between the three groups (II, ID and DD), respectively. At baseline, multiple linear regression analysis including the above-mentioned putative risk factors revealed that albuminuria, short stature, and male gender independently predict an enhanced decline in GFR [R2 (adjusted) = 0.33; P < 0.002]. During the follow-up period, only albuminuria acted as an independent progression promoter [R2 (adjusted) = 0.37; P < 0.0001].ConclusionsOur study revealed a rather slow progression of kidney disease in normotensive type 1 diabetic patients with diabetic nephropathy. Albuminuria, short stature, and male gender act as progression promoters in such patients

Metformin and cardiorenal outcomes in diabetes : a reappraisal

The guidance issued to the pharmaceutical industry by the US Food and Drug Administration in 2008 has led to the publication of a series of randomised, controlled cardiovascular outcomes trials with newer therapeutic classes of glucose‐lowering medications. Several of these trials, which evaluated the newer therapeutic classes of SGLT2 inhibitors and GLP‐1 receptor agonists have reported a reduced incidence of major adverse cardiovascular and/or renal outcomes, usually relative to placebo and standard of care. Metformin was the first glucose‐lowering agent reported to improve cardiovascular outcomes in the UK Prospective diabetes Study (UKPDS) and thus became the foundation of standard care. However, as this clinical trial reported more than 20 years ago, differences from current standards of trial design and evaluation complicate comparison of the cardiovascular profiles of older and newer agents. Our article revisits the evidence for cardiovascular protection with metformin and reviews its effects on the kidney.Publisher PDFPeer reviewe

Urinary proteome analysis enables assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria

<p>Abstract</p> <p>Background</p> <p>Previously the angiotensin II receptor blocker Irbesartan has been demonstrated to reduce the risk for progression from microalbuminuria to macroalbuminuria in type 2 diabetic patients. The purpose of this study was to evaluate the effect of treatment with Irbesartan in type 2 diabetic patients with microalbuminuria on the urinary proteome.</p> <p>Methods</p> <p>High-resolution capillary-electrophoresis coupled to mass-spectrometry (CE-MS) was used to profile the low-molecular-weight proteome in urine of a subgroup of patients from a two year randomized irbesartan versus placebo therapy trial, which included hypertensive type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication (IRMA2-substudy).</p> <p>Results</p> <p>We demonstrate that the therapy with 300 mg Irbesartan daily over a period of two years results in significant changes of the urinary proteome. Both, a classifier developed previously that consists of urinary peptides indicative of chronic kidney disease, as well as several individual peptides changed significantly after treatment. These changes were not observed in the placebo-treated individuals. Most prominent are changes of urinary collagen fragments associated with progression of diabetic nephropathy, indicating normalization in urinary peptides.</p> <p>Conclusion</p> <p>CE-MS analysis of urine enabled identification of peptides as potential surrogate markers for renoprotection in microalbuminuric type 2 diabetic patients, which show persistent improvement after longterm treatment with Irbesartan. The results suggest that a major benefit of treatment by Irbesartan may be improvement of collagen turnover, reduction of fibrosis. They further suggest that urinary proteome analysis could be utilized to assess potential benefit of therapeutic intervention, providing statistically significant results even on a small population.</p