What is the role of omega-3 fatty acids in the prevention of albuminuria in diabetic and cardiovascular disease patients?
Diabetes mellitus (DM) is the main cause of chronic kidney disease (CKD) worldwide. The prevalence of diabetic nephropathy, a type of CKD, has increased among patients with type 2 diabetes. Diabetic CKD (diabetic nephropathy) is the main cause of kidney failure, representing over 50% of cases of terminal stage kidney disease. While albuminuria is common among patients with type 2 diabetes, it also occurs among patients with hypertension and healthy subjects. Furthermore, albuminuria is a marker for general vascular dysfunction and an independent predictor for cardiovascular morbidity and mortality in these groups of patients.
Thus diabetic nephropathy (DN) could be related to chronic inflammation leading to fibrosis and albuminuria. The increased expression of proinflammatory cytokines in different kidney structures and cells and the effects of therapeutic strategies related to modulating the inflammatory response can play a significant role in the pathogeny of DN and might be at least partly responsible for the development and progression of kidney failure in DM if not corrected, leading to the final stage of the disease, dialysis or transplant.
Treatment to prevent the progression of albuminuria currently uses non-steroidal angiotensin-converting enzyme inhibitors (NSAIDs) or angiotensin II receptor blockers (ARBs) to inhibit the renin-angiotensin-aldosterone system (RAAS). Both are considered standard treatments in diabetic patients to reduce albuminuria and associated cardiovascular morbidity and mortality. Current therapies for CKD depend on blocking the RAAS. Although RAAS inhibition delays the progress of CKD, it cannot reverse fibrosis; thus there is a need to develop safe and effective therapies to prevent CKD. Although treatment for hyperlipidemia and hyperglycaemia have managed to reduce the incidence of cerebrovascular accident, myocardial infarction and amputations in diabetic subjects, optimum management of these risk factors has not reduced renal complications, which is a reflection of inadequate treatment to reduce the degree of albuminuria and its associated complications. Among these alternatives, the effect of omega-3 fatty acids has been studied on DN. Various clinical trials have been performed suggesting that omega-3 fatty acids are beneficial in correcting albuminuria in diabetic patients, although the results were not definitive due to a fault in the trial methodology. Welty et al. performed a clinical trial on 262 individuals (diabetics and non-diabetics) and showed that administering eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for a year slowed the progression of albuminuria in early stages of the disease. The trial included diabetic patients with coronary heart disease treated with ACE inhibitors with an albumin/creatinine ratio (ACR) of <30 µg/mg. Subjects treated with EPA/DHA showed a significant drop in their ACR compared to the control patients. Furthermore, significantly more (3 times more) patients treated with EPA/DHA (3.36 g EPA/DHA daily) showed a reduction in their ACR compared to the control group and three patients treated with EPA/DHA changed their category from >30 to <30 μg/mg, while no control patients showed a reduction in their ACR. These results suggest there is a benefit to and even a reduction in the ACR in diabetic patients treated with EPA/DHA at an early stage of the disease in patients with a ACR <30 μg/mg and those with micro-albuminuria (ACR >30).