Clinical significance of renal function in hypertensive patients at high risk: results from the INSIGHT trial.
BACKGROUND
Increasing evidence suggests renal involvement in hypertension-related cardiovascular and cerebrovascular complications. To assess this role of renal function in more detail, we studied the evolution of renal function and the relationship of renal function with mortality and morbidity in the Intervention as a Goal in Hypertension Treatment (INSIGHT) study.


METHODS
The INSIGHT study was a double-blind, randomized, multicenter trial in patients with hypertension and at least 1 additional cardiovascular risk factor. Treatment consisted of nifedipine gastrointestinal therapeutic system, 30 mg/d, or hydrochlorothiazide-amiloride (25 mg/d of hydrochlorothiazide and 2.5 mg/d of amiloride hydrochloride). Primary outcome was a composite of cardiovascular death, myocardial infarction, heart failure, and stroke. Renal function was assessed by measuring creatinine clearance, serum creatinine level, and serum uric acid level and by the presence of proteinuria.


RESULTS
Creatinine clearance fell more in nifedipine recipients than in hydrochlorothiazide-amiloride recipients. Renal insufficiency developed in 2% of nifedipine recipients and 5% of hydrochlorothiazide-amiloride recipients. Primary outcomes occurred in 15% of patients with increased serum creatinine levels and 6% of patients with normal levels (odds ratio [OR] 2.89; 95% confidence interval [CI], 1.92-4.36; P<.001). Primary outcomes were more likely in patients with low creatinine clearance (<60 mL/min) than in those with higher clearances (9% vs 5%, respectively [OR, 1.51, 95%CI, 1.22-1.88; P<.001]).


CONCLUSIONS
Renal function is an important predictor of risk in hypertensive patients at high risk. Antihypertensive treatment with a long-acting dihydropyridine calcium channel blocker may better preserve renal function than would treatment with diuretics.
de Leeuw
Peter W
PW
Department of Medicine, University Hospital Maastricht, Maastricht, The Netherlands. p.deleeuw@intmed.unimaas.nl
Ruilope
Luis M
LM
Palmer
Christopher R
CR
Brown
Morris J
MJ
Castaigne
Alain
A
Mancia
Giuseppe
G
Rosenthal
Talma
T
Wagener
Gilbert
G
D000368:Aged; D000584:Amiloride / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000517:prevention & control; D012307:Risk Factors; D014665:Vasodilator Agents / Q000627:therapeutic use
D014665:Vasodilator Agents; D006852:Hydrochlorothiazide; D000584:Amiloride; D003404:Creatinine; D009543:Nifedipine