Methods of cardio-renal protection in non-diabetic chronic nephropathies.
Angiotensin II (AII), the main effector of the Renin Angiotensin System (RAS), plays a central role in the hemodynamic and non-hemodynamic mechanisms of chronic renal disease and is currently the main target of interventions aimed to prevent the onset and progression of chronic nephropathies to end stage renal disease (ESRD). In addition to ameliorate glomerular hyperfiltration and size-selectivity, reduce protein traffic and prevent glomerular and tubulo-interstitial toxicity of ultrafiltered proteins, RAS inhibitors also limit the direct nephrotoxic effects of AII. Thus, both ACE inhibitors (ACEi) and AII antagonists (ATA) exert a specific nephroprotective effect in both experimental and human chronic renal disease. This effect is time-dependent and is observed across degrees of renal insufficiency. Forced ACEi or ATA up-titration above doses recommended to control arterial hypertension and combined treatment with both agents allow to optimise A II inhibition and maximize renoprotection. Multifactorial interventions combining RAS inhibition to treatments targeted also to non-RAS mechanisms may even achieve regression of glomerulosclerosis and chronic tubulo-interstitial injury. Studies are needed to assess whether renal damage can be reverted to such a point that renal function may be fully prevented from worsen, and possibly improve. The economic impact of even a partial improvement would be enormous. Moreover, chronic renal insufficiency is an independent risk factor for cardiovascular disease and effective nephroprotection may also decrease the excess cardiovascular morbidity and mortality associated with chronic nephropathies. In patients with renal insufficiency ACEi are even more cardioprotective than in those without, and are well tolerated. Thus, RAS inhibitor therapy should be offered to all renal patients without specific contraindications, including those closer to renal replacement therapy.
Ruggenenti
P
P
Department of Medicine and Transplantation, Azienda Ospedaliera Ospedali Riuniti, Bergamo, Italy.
Remuzzi
G
G
D000804:Angiotensin II / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000517:prevention & control*; D005921:Glomerulonephritis / Q000150:complications / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II