Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial

Abstract

Aims/hypothesis The purpose of this study was to evaluate the optimal renoprotective effect of ultrahigh doses of lisinopril, as reflected by short-term changes in urinary albumin excretion rate (UAER), in type 1 diabetic patients with diabetic nephropathy. Methods At the Steno Diabetes Center, 49 type 1 diabetic patients with diabetic nephropathy completed this doublemasked randomised crossover trial consisting of an initial washout period followed by three treatment periods each lasting 2 months, where all patients received lisinopril 20, 40 and 60 mg once daily in randomised order in addition to slow-release furosemide. Allocation was concealed by sequentially numbered opaque sealed envelopes. UAER, 24 h ambulatory blood pressure (ABP) and estimated GFR were determined at baseline and after each treatment period. Reductions in UAER from baseline were 63%, 71% and 70%, respectively, with the increasing doses of lisinopril (p<0.001). Compared with lisinopril 20 mg there was a further reduction in UAER of 23% with lisinopril 40 mg and 19% with 60 mg, p<0.05. ABP was reduced from baseline by 10/5, 13/7 and 12/7 mmHg (p<0.001 vs baseline, p<0.05 for diastolic ABP 20 vs 40 mg, otherwise NS between doses). The difference in UAER between 20 and 40 mg lisinopril was significant after adjustment for changes in ABP (p<0.01). Two patients were excluded from the study because of an increase in plasma creatinine and one because of high BP; otherwise the study medication was well tolerated with few, mild, dose-independent adverse effects. Conclusions/interpretation Lisinopril 40 mg once daily is generally safe and offers additional reductions in BP and UAER in comparison with the currently recommended dose of 20 mg. Lisinopril 60 mg offers no further beneficial effect.Trial registration: ClinicalTrials.gov NCT00118976 Funding: This study was financed out of local funds and was not supported by the medical industry.

Optimal antiproteinuric dose of aliskiren in type 2 diabetes mellitus: a randomised crossover trial

“…Dosing of antiproteinuric RAAS blockade was recently discussed [8] and has so far been investigated in a fraction of the treatments used today [3,9].…”

“…The trials used antihypertensive doses not necessarily optimal for renoprotection. Several dosage studies [3,4] have demonstrated dosedependent antiproteinuric effects. After the introduction of the renin inhibitor aliskiren and evidence of its antiproteinuric effects [2,5] we aimed to investigate the antiproteinuric effect of increasing doses of aliskiren, by comparing urinary albumin excretion rate (UAER) during placebo and after 2 months of treatment with aliskiren 150 mg, 300 mg or 600 mg once daily.…”

Optimal dose of angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker for renoprotection

“…More recently, 13 in a single centre, double-blind, randomized cross-over trial, 49 patients with type 1 diabetes and nephropathy received three treatment periods with 20, 40 or 60 mg/day of lisinopril. Each period lasted for 2 months.…”

Diabetes und Niere – Update 2009

“…Es stellt sich immer wieder die Frage, ob möglicherweise höhere Dosen von ACE-Hemmern zusätzliche nephroprotektive Effekte haben. Diese Fragestellung wurde bei Patienten mit Typ-1-Diabetes, die an einer Nephropathie litten, für den ACE-Hemmer Lisinopril in einer randomisierten "Cross-over-Studie" untersucht [30]. Hierbei zeigte sich, dass Lisinopril 40 mg einmal täglich im Vergleich zu Lisinopril 20 mg einmal täglich zu einer zusätzlichen Reduktion des Blutdrucks sowie der Albuminurieausscheidung ohne Zunahme der Nebenwirkung führte [30].…”