title: Individual titration for maximal blockade of the renin-angiotensin system in proteinuric patients: a feasible strategy?
abstract: Agents that interfere with the renin-angiotensin system (RAS) reduce proteinuria and afford renal protection. The combination of different measures that serve maximization of RAS blockade is thought to improve the antiproteinuric efficacy. The feasibility and the efficacy of such a combination strategy were studied in nondiabetic patients with residual proteinuria during previous RAS blockade by individual antiproteinuric titration. Previous medication was replaced by irbesartan 300 mg combined with a diuretic. Lisinopril was added in increasing doses until a maximal dose of 40 mg/d. Titration stopped when target proteinuria (< 1 g/d) was reached or further dose titration was not tolerated because of side effects. Residual proteinuria (median, 3.2 g/d; 95% confidence interval, 1.8 to 5.2 g/d) was significantly reduced with 55.6% (95% confidence interval, 16.0 to 73.2%; P < 0.02) on the maximal additional tolerated dose of lisinopril. The maximal dose of lisinopril was 10 mg in two of eight, 20 mg in two of eight, 30 mg in one of eight, and 40 mg in three of eight patients. At this dose, target proteinuria of < 1 g/d was reached in two of eight patients. The number of patients with adverse events during dose titration was five of eight patients: two had cough; two had hyperkalemia (> 5.5 mmol/L), one of whom had > 50% increase of serum creatinine; and one had dizziness. In conclusion, individual titration for maximal RAS blockade, entailing dose titration of angiotensin-converting enzyme inhibitors on top of high-dose angiotensin II antagonists with diuretic, induces further reduction of residual proteinuria. However, this occurs at the expense of adverse events. To further improve renoprotective treatment strategies, it is important to explore other modes of antiproteinuric intervention in patients with residual proteinuria during RAS blockade.
authors.affiliation: Division Nephrology, Department of Medicine, Groningen University Medical Center, Groningen, The Netherlands. l.vogt@int.azg.nl
authors.forename: Liffert
authors.initials: L
authors.lastname: Vogt
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077405:Irbesartan; D007674:Kidney Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D007677:Kidney Function Tests; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018579:Patient Selection; D011336:Probability; D011507:Proteinuria / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D018570:Risk Assessment; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D016482:Urinalysis
chemical_list: D001713:Biphenyl Compounds; D013777:Tetrazoles; D017706:Lisinopril; D000077405:Irbesartan