Effect of Lisinopril on the progression of renal insufficiency in mild proteinuric non-diabetic nephropathies.
BACKGROUND
The aim of the study was to determine whether Lisinopril, an ACE-inhibitor (ACEi), was more effective than other antihypertensive agents in slowing the progression of non-diabetic chronic renal diseases in patients with baseline proteinuria < or =1.0 g/day.


METHODS
In an open, multicentre study all eligible patients entered a 3 months run-in phase during which antihypertensive therapy (with exclusion of ACEi) was adjusted in order to obtain a supine diastolic blood pressure < or =90 mmHg and urinary protein excretion and renal function stability were verified. One hundred and thirty-one patients with chronic renal insufficiency (Clcr between 20-50 ml/min) because of primary renoparenchymal diseases and proteinuria < or =1.0 g/day, were randomized to Lisinopril (L=66) or alternative antihypertensive therapy (C=65). Changes in renal function were assessed by inulin (Clin) clearance.


RESULTS
During the follow-up period of 22.5+/-5.6 months, Clin did not change significantly in group L (-1.31+/-0.6 ml/min/1.73 m(2)) differing significantly from group C in which it declined markedly (-6.71+/-3.6 ml/min/1.73 m(2)) (P<0.04). Seven patients experienced adverse events that prompted discontinuation of treatment: four in group L and three in group C; in addition seven patients showed severe deterioration in renal function requiring dialysis: two in group L and five in group C. The overall risk of the combined end-points: need for dialysis or halving of GFR was significantly higher in group C versus group L. During the study the mean value for systolic blood pressure was 137.8+/-14.6 SD mmHg in group L and 140.8+/-14.1 SD mmHg in group C; the mean difference between groups, during and at the end of the study, was 2 mmHg (NS). The mean diastolic blood pressure during the study was 83.8+/-8.6 SD mmHg in group L and 84.3+/-7.56 SD mmHg in group C; during and at the end of the study the mean diastolic difference between groups was 1 mmHG:


CONCLUSIONS
This study, employing a sensitive measurement of renal function and with similar blood pressure in both groups, provides support to the hypothesis that ACEi have a specific renoprotective effect, in addition to blood pressure control, also in patients with mild proteinuria.
Cinotti
G A
GA
Division of Nephrology, Dipartimento de Scienze Cliniche, University of Roma La Sapienza, Policlinico Umberto I, R-00161 Rome, Italy.
Zucchelli
P C
PC
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003971:Diastole; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000652:urine*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020011:Protective Agents / Q000627:therapeutic use*; D011507:Proteinuria / Q000209:etiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D020011:Protective Agents; D017706:Lisinopril