title: Therapeutic approaches in lowering albuminuria: travels along the renin-angiotensin-aldosterone-system pathway.
abstract: Achieving optimal blood pressure and albuminuria control is a major therapeutic treatment goal in patients with renal insufficiency. Angiotensin-converting enzyme-inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) are the mainstay of therapy in these patients. However, despite these therapies many patients remain at high risk of renal or cardiovascular disease that shows a relationship with albuminuria. Various approaches have been tested to maximize the efficacy of ACEI and ARB. Increasing the dose of an ACEI or ARB beyond the maximal registered antihypertensive dose causes a distinct decrease in albuminuria without additional effects on blood pressure. The combination of an ACEI and ARB is another possibility to further reduce albuminuria. However, the alleged beneficial effects on hard renal and cardiovascular outcome are not unambiguously demonstrated. Adding a direct renin inhibitor to an ACEI or ARB has been shown to lower albuminuria in patients with and without diabetes. Long-term trials are currently under way to determine the effects of direct renin inhibition on clinical outcomes. Volume excess has been shown to blunt the blood pressure and albuminuria response to ACEI or ARB therapy. Intervening in volume status by means of restricting dietary sodium intake or diuretic therapy has convincingly been shown to lower blood pressure and albuminuria. Whether this strategy translates into a reduction in the risk of renal or cardiovascular events has not (yet) been investigated in prospective randomized trials. Various options are at hand which have been shown to maximize the blood pressure and albuminuria response to ACEI and ARB treatment. However, long-term studies supporting the benefits of these strategies on hard renal and cardiovascular outcomes are warranted.
authors.affiliation: Department of Clinical Pharmacology, University Medical Centre Groningen, University of Groningen, the Netherlands. h.j.lambers.heerspink@med.umcg.nl
authors.forename: Hiddo J Lambers
authors.initials: HJ
authors.lastname: Heerspink
mesh_terms: D000419:Albuminuria / Q000188:drug therapy*; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy; D000075202:Contraindications; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012982:Sodium, Dietary; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D012982:Sodium, Dietary; D000092502:Renin Inhibitors