Dual Blockade of the Renin-Angiotensin System

Abstract

The prevalence of chronic renal diseases is increasing worldwide. There is a great need to identify therapies that arrest disease progression to end-stage renal failure. Inhibition of the renin-angiotensin system both by angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists is probably the best therapeutic option available. Several large, multicenter studies have indeed shown a significant reduction in the risk for doubling baseline serum creatinine or progression toward end-stage renal failure in patients who do and do not have diabetes and have chronic nephropathies that are treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists. However, the number of patients who reach end-stage renal failure is still considerably high. Significant reduction of the incidence of ESRD is likely to be achieved in the near future for chronic nephropathies, provided that the degree of renoprotection can be improved. This goal may be attainable with a more complex strategy than with a single or dual pharmacologic intervention on the renin-angiotensin system. Strict control of BP and protein excretion rate, lowering of blood lipids, tight glucose control for individuals with diabetes, and lifestyle changes form part of the future multimodal protocol for treatment of patients with chronic nephropathies.

Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines

“…However, renal protection of drug faces the challenge of side effect (dry cough), as well as patient resistance. Renal protection for DN benefits from combination of drugs (Codreanu et al, 2005) and multifactoral treatment (Fioretto and Solini, 2005), therefore development of a new drug or food supplement that acts on multiple factor of DN, is very much needed.…”

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction

“…Impaired renal function inhibits the production of various metabolites in the body and aggravates renal fibrosis in CKD. The uremic toxins that accumulate during the early stages of CKD promote renal cell apoptosis via transforming growth factor-␤1 (TGF-␤1) (6). Renal dysfunction in CKD is further promoted by signaling via the renin-angiotensin-aldosterone system (7).…”

The potential of small chemical functional groups for directing the differentiation of kidney stem cells

“…For this reason, the mainstay of treatment for diabetic and some non-diabetic nephropathies is RAAS inhibition with ACEIs (angiotensin-converting-enzyme inhibitors) and/or ARBs (AngII receptor blockers). Although these drug therapies are limited in their ability to reverse chronic renal disease, especially in cases where scarring has already occurred, they are very effective at preventing further damage, and can thus significantly delay the onset of ESRD [15][16][17]. However, not all patients respond to ACEI/ARB therapy, and some continue to secrete high levels of aldosterone [18], whereas others are unable to continue treatment due to hyperkalaemia and other side effects.…”