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A Journal on Internal Medicine
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,236
HYPERTENSION, DIABETES AND RENAL DISEASES
Minerva Medica 2004 October;95(5):395-410
Renoprotection by blockade of the renin-angiotensin-aldosterone system in diabetic and non-diabetic chronic kidney disease. Specific involvement of intra-renal angiotensin-converting enzyme activity in therapy resistance?
Vogt L., Kocks M. J. A., Laverman G. D., Navis G.
Data of numerous clinical trials show that lowering of blood pressure is prerequisite for reducing the rate of renal function loss in chronic renal disease. There is evidence supporting that blood pressure lowering obtained by intervention in the renin-angiotensin-aldosterone system (RAAS) has an additive renoprotective effect over reduction of blood pressure alone, both in diabetic and non-diabetic renal diseases. The main evidence for renoprotective action of RAAS blockade is provided by its consistent antiproteinuric action, which cannot completely be attributed to the reduction in blood pressure. Indeed, proteinuria reduction during therapy is the single most important factor predicting the renal prognosis, independent from the class of drugs used. Yet, still patients progress to end-stage renal disease. In this review, individual differences in therapy response and possibilities to overcome therapy resistance to RAAS blockade are discussed. Experimental data from studies in rats suggest a specific involvement of intrarenal factors, particularly of preexisting renal damage and renal angiotensin-converting enzyme (ACE) activity, in therapy resistance. Identification of such factors in individual renal patients provides mechanisms by which renoprotective strategies fail to overcome therapy resistance. This prompts for a dual approach to improve renoprotection, namely unravelling these specific intrarenal mechanisms on the one hand, and development of better strategies for early detection of renal risk on the other hand.