Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis

<div><p>Background</p><p>Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression.</p><p>Study design</p><p>Systematic review and meta-analysis.</p><p>Population</p><p>Adults with DKD (either secondary to type 1 or 2 diabetes mellitus)</p><p>Search strategy and sources</p><p>Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction.</p><p>Intervention</p><p>Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination.</p><p>Outcomes</p><p>Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.</p><p>Results</p><p>From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m²; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking.</p><p>Limitations</p><p>Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.</p><p>Conclusions</p><p>In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.</p></div

Effect of antioxidants vs. control on urinary albumin (2a); sensitivity analyses on separate effects by Vitamin E (2b) and Vitamin C supplements (2c).

<p>Effect of antioxidants vs. control on urinary albumin (2a); sensitivity analyses on separate effects by Vitamin E (2b) and Vitamin C supplements (2c).</p

Effect of antioxidants vs. control on renal function (GFR).

<p>Effect of antioxidants vs. control on renal function (GFR).</p

Summary of findings (GRADE) table.

<p>Summary of findings (GRADE) table.</p

Summary of main characteristics and findings of the included studies.

<p>Summary of main characteristics and findings of the included studies.</p

Publication bias (funnel plot) for urinary albumin.

<p>Publication bias (funnel plot) for urinary albumin.</p

Novel avenues for treating diabetic nephropathy: new investigational drugs

<p><b>Introduction</b>: At present, treatment of diabetic kidney disease (DKD) is still mainly based on drugs acting on glycemic and blood pressure control, as there is no validated therapy able to halt the progression of renal failure. Because of the high incidence of DKD, due to the increase of diabetes mellitus in general population, new therapeutic strategies are needed.</p> <p><b>Areas covered</b>: We analysed ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed, dealing with new therapies for DKD.</p> <p><b>Expert opinion</b>: Among the drugs currently being explored, the most promising molecules are those that interfere with glucose-dependent pathways, in particular polyol, protein kinase, hexosamine and AGEs metabolic pathways, and impaired renal vascular regulation. One of the recent goals achieved by molecular biology is the development of monoclonal antibodies able to interfere with extracellular matrix accumulation and fibrosis. Other interesting therapies are under investigation and further studies with a greater number of patients will establish a better approach for diabetic nephropathy.</p