Review: Preventing End-Stage Renal Disease in Diabetic Patients — Dual Blockade of the Renin-Angiotensin System (Part II)

Abstract

Diabetic nephropathy is a major cause of diabetes related morbidity and mortality. The first part of the current review was published in the last issue of this journal and discussed the important role of the renin-angiotensin system (RAS) in diabetic nephropathy and the genetic influence on development of endstage renal disease (ESRD) in diabetic patients. This second part of the review focus on the potential improvement of the current treatment strategy to slow down the loss of kidney function using dual blockade of the RAS with both ACE-inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs). Substantial evidence from short-term studies using surrogate endpoints indicates a beneficial impact of dual blockade of the RAS, not obtainable with single agent blockade alone, both in diabetic and non-diabetic renal disease. This conclusion has been confirmed and extended in a longterm trial with regard to prevention of ESRD in non-diabetic renal disease. Results indicate that dual blockade of the RAS may further slow down, but not arrest progressive loss of renal function. However, studies defining the optimal dose of ACE-I / ARBs without additional adverse effects are essential to ensure relevant comparison with dual blockade therapy. Trials using primary renal endpoints in diabetic nephropathy are still needed, and will finally establish the role of dual blockade of the RAS in a clinical setting.

Hydrogen Sulfide: Recent Progression and Perspectives for the Treatment of Diabetic Nephropathy

“…Over-activation of intrarenal RAS aggravates diabetic nephropathy due to a fact that inhibition of RAS retards the progression of diabetic nephropathy in animal models and clinical trials [22,72]. It is likely that intrarenal RAS is activated in patients suffering from diabetes, thereby RAS blockers have the benefits for abnormal glomerular structures in patients with diabetic kidney disease [73,74,75]. Present researches recommend that RAS blockers can relieve the nephropathy for albuminuric patients with diabetes [14].…”

Diabetic threesome (hyperglycaemia, renal function and nutrition) and advanced glycation end products: evidence for the multiple-hit agent?

“…Haemodynamic changes are represented initially by increased intraglomerular pressure, which is independent of systemic blood pressure and can be detected quite early after the onset of the disease. Blockade of the renninangiotensin system (by angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers) has been convincingly shown to delay the onset and progression of diabetic nephropathy, not only by its effect on filtration pressure but also by its non-haemodynamic effects (suppression of ROS production and cytokine release) (100)(101)(102)(103) . All parts of nephron (the vasculature, glomerular filtration barrier, tubuli and also the kidney interticium) undergo pathological changes during the course of diabetic nephropathy.…”

Albuminuria: A Great Risk Marker, but an Underestimated Target in Diabetes

“…The most tested combination is ACE inhibitors plus ARBs. This combination not only shows an enhanced effect on albuminuria lowering (24), but it also shows an enhanced effect on long-term renal outcome in nondiabetic renal disease patients (25). The latter combination needs to be confirmed in other trials.…”