Effects of Cilazapril and Amlodipine on Kidney Function in Hypertensive NIDDM Patients

Abstract

Contrasting information has been reported concerning the course of renal function in NIDDM with hypertension alone or in association with renal damage. The aim of the present study was to elucidate the course of the glomerular filtration rate (GFR) in hypertensive NIDDM patients during antihypertensive therapy. Furthermore, we compared the effects of ACE inhibitors (cilazapril, Inibace, Roche, Milan, Italy) and Ca(2+)-channel blockers (amlodipine, Norvasc, Pfizer, Rome, Italy). Of the hypertensive NIDDM patients attending the outpatient's clinic of the internal medicine departments of the University of Padova and Sassari, 44 participated in the present study. Of these patients, 26 were normoalbuminuric and 18 microalbuminuric. They were randomly treated with either cilazapril or amlodipine. The target of antihypertensive treatment was a value < 140 mmHg for systolic and 85 mmHg for diastolic blood pressure (BP). Microalbuminuria was defined as an albumin excretion rate (AER) between 20 and 200 micrograms/min. GFR was measured by plasma clearance of 51Cr-labeled EDTA at baseline and every 6-12 months during a 3-year follow-up interval. A significant decrease was observed in the values of GFR, AER, and systolic and diastolic BP in normoalbuminuric and microalbuminuric patients during antihypertensive therapy. The GFR fall in the overall population of NIDDM patients was significantly and inversely related to the decrease of mean BP (diastolic + 1/3 pulse pressure) (r = -0.80, P < 0.0001) but not to that of HbA1c, triglycerides, and BMI. The GFR decline (mean +/- SE) per year in the normoalbuminuric patient was 2.03 +/- 0.66 ml.min-1 x 1.73 m-2 (95% CI 0.92-3.17) during cilazapril and 2.01 +/- 0.71 ml.min-1 x 1.73 m-2 (95% CI 0.82-3.11) during amlodipine therapy. The GFR decline per year in the microalbuminuric patient was 2.15 +/- 0.69 ml.min-1 x 1.73 m-2 (95% CI 0.86-3.89) during cilazapril and 2.33 +/- 0.83 ml.min-1 x 1.73 m-2 per year (95% CI 1.03-3.67) during amlodipine therapy. Cilazapril and amlodipine lowered AER to a similar extent in normoalbuminuric and microalbuminuric patients. No significant changes were observed concerning other clinical and biochemical features between the two antihypertensive therapies and particularly HbA1c, BMI, triglycerides, and cholesterol plasma values. These results support the tenet that arterial hypertension plays a pivotal role in contributing to renal damage in NIDDM, even when AER is normal. However, the degree of BP control, with both cilazapril and amlodipine, can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy.

Treatment of hypertension in diabetic patients with nephropathy

“…Although the FACET and ABCD trials showed the beneficial cardiovascular effects of ACEIs over dhCCBs, other studies, such as HOT and Syst-Eur [64], showed the substantial safety and efficacy of CCBs in preventing cardiovascular end points in type 2 diabetes. With respect to renal effects, studies by Velussi et al [36] and Fogari et al [25], as well as analysis of renal end points in the ABCD trial [48], showed similar effects of ACEIs and dhCCBs on the course of nephropathy, except for effects on proteinuria. Whether the weaker antiproteinuric effect of dhCCB translates into a worse nephroprotective outcome after a longer follow-up remains to be established.…”

“…Despite optimism about the use of ACEIs raised by placebocontrolled studies by Ravid et al [29], showing renoprotective effects of 7 years of treatment with enalapril in normotensive MA patients, and some other studies (follow-up ≥ 12 months) suggesting that ACEIs could be superior to other regimens in hypertensive patients in various stages of renal involvement [30][31][32][33][34][35], other studies reported similar nephroprotection after ACEIs, to that after nifedipine in normotensive [17], or to that of amlodipine [36], nitrendipine [37], or atenolol [38] in hypertensive patients. In type 2 diabetes, much new information has been recently communicated.…”

The calcium channel blocker controversy in patients with diabetic nephropathy: Is there an issue?

“…Some studies have reported a similar renoprotective capacity of CCBs and ACE inhibitors in diabetic nephropathy [13][14][15]. The results of long-term studies are, nevertheless, required to prove whether or not both classes of drugs can be used as first-step therapy in diabetic nephropathy.…”

“…The good effect of the dihydropyridine could, in this case, be mostly ascribed to a significantly better BP control when nitrendipine, alone or in combination, was administered. The recent presentation of data from the AASK study [17], in which amlodipine in combination with non-ACE inhibitor therapy was significantly worse than an ACE inhibitor-based combination therapy (Data presented at the American Society of Nephrology meeting, Toronto, October [11][12][13][14][15][16]2000 ) in blacks with renal disease of various origins, does not seem to confirm the equality among ACE inhibitors and CCBs. This year data from the IDNT study [18] will be presented, and data comparing amlodipine and irbesartan (in combination in most cases) in type 2 diabetic nephropathy will be revealed and contribute to clarify this issue.…”

Antihypertensive drugs and the kidney

“…Although some small studies have found that CCBs and ACE inhibitors are equally renoprotective [37,38], others have shown an increase in proteinuria and worsening renal function in patients treated with CCBs [39,40].…”