Renal and cardio-protective effects of direct renin inhibition: a systematic literature review.
BACKGROUND
Blockade of the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step by means of renin inhibition has led to the development of direct renin inhibitors (DRIs). Given the renal and cardioprotective effects of RAAS blockade by angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, DRIs may increase the armamentarium for further organ protection. Over the last two decades the effects of DRIs on biomarkers for renal and cardiovascular disease have been investigated. This systematic review aims to delineate the effects of DRIs on surrogate markers of renal and cardiovascular function.


METHODS
MEDLINE and previous systematic reviews were searched for articles reported between 1980 and 2008. A standardized dataset was extracted from articles describing the effects of DRIs on markers of renal and cardiac damage and hard outcomes.


RESULTS
Fifty-two articles were included. Blood pressure reductions were generally insufficient using early generation DRIs. However, recent DRIs have greater blood pressure-lowering effects. Preclinical and clinical studies showed profound effects of DRIs on markers of renal function, including clear increases in renal plasma flow and reductions in albuminuria. These effects were observed either alone or in combination with other RAAS inhibitors and suggest potential large renal protective benefit. DRIs improved hemodynamic cardiovascular parameters, such as total peripheral resistance, arterial pressure and left ventricular mass index, to a similar extent as those observed with other RAAS inhibitors. Furthermore, addition of DRIs to optimal heart failure treatment resulted in further reductions in B-type natriuretic peptide.


CONCLUSIONS
Evidence from preclinical and clinical studies suggests that DRIs may have renal and cardiovascular effects beyond their ability to lower blood pressure. Results of ongoing hard outcome trials are awaited to definitively assess the renal and cardio-protective effects of these agents.
Lambers Heerspink
Hiddo J
HJ
Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Perkovic
Vlado
V
de Zeeuw
Dick
D
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D016206:Databases, Bibliographic; D004195:Disease Models, Animal; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007677:Kidney Function Tests; D011945:Receptors, Angiotensin / Q000187:drug effects; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D000092502:Renin Inhibitors
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D054316:Biomarkers, Pharmacological; D004338:Drug Combinations; D011945:Receptors, Angiotensin; D012083:Renin; D000092502:Renin Inhibitors