lacidipine and Albuminuria

This study was carried out to assess whether with a similar degree of blood pressure reduction, Lisinopril compares favorably or otherwise with lacidipine in respect of effects on urinary albumin excretion and renal function as assessed by creatinine clearance, plasma creatinine, urea and electrolytes. Thirty hypertensive diabetic nephropathy patients with moderate hypertension were studied. After a 2-week washout period, they were allocated into two groups matched at baseline for age, sex, weight, blood pressure, and urinary albumin excretion rate as well as creatinine clearance. There were 8 males and 7 females in each group. One group received lisinopril (with furosemide if needed to control BP) and the other group received lacidipine. Staged increases in doses of antihypertensives were used until BP was controlled or maximum dose of 40 mg/day lisinopril or 8 mg/day lacidipine was reached. Furosemide was added to lisinopril if BP was not controlled at 40 mg/day. These medications were given for 12 weeks at the end of which measurements done at baseline were repeated. Comparison of baseline and end of study values of these parameters within the groups and between the two groups were made. Lisinopril group and lacidipine group achieved similar and highly significant reduction in blood pressure levels P < 0.001. There was reduction in urinary albumin excretion rate in both groups but this only reached statistical significance in the lisinopril group [480] [269] mg/day vs. 315 [202] mg/day P < 0.05] while for the lacidipine group it was not significant [491] [257] mg/day vs. 335 [182] mg/day P > 0.05]. However, comparison of albumin excretion rate between both groups at baseline and at end of the study did not show any significant difference, P > 0.1. With both drugs there is a tendency for creatinine clearance to increase and plasma creatinine to drop while plasma potassium tended to rise more with lisinopril than lacidipine but differences within and between both groups, did not reach statistical significance P > 0.05. In conclusion, blood pressure reduction was comparable in both drugs; both drugs reduced albuminuria but lisinopril appeared superior. Treatment with both drugs tended to increase creatinine clearance but both had no significant effects on blood sugar.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Blood Pressure; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dihydropyridines; Disease Progression; Female; Humans; Hypertension; Lisinopril; Male; Metabolic Clearance Rate; Middle Aged; Potassium; Prospective Studies; Treatment Outcome; Urea

There are few studies on the use of dihydropyridine calcium antagonists in hypertensive patients with moderate renal insufficiency. We undertook an open study on the effects on renal function, albumin excretion and blood pressure of the slow-onset, long-acting dihydropyridine calcium antagonist, lacidipine, in 14 patients with stable, chronic renal insufficiency (mean assessed GFR 0.78 ml/s, range 0.50-1.17 ml/s) and moderate hypertension. Following a 2 week washout phase, lacidipine was administered for 24 weeks in a dose of 2 mg/day with the dose being titrated at 2 weekly intervals to a maximum of 6 mg/day in order to achieve adequate blood pressure control. Frusemide was introduced if blood pressure was not controlled on the maximum lacidipine dose. Blood pressure, creatinine clearance, 24 h urinary albumin excretion and plasma creatinine and albumin concentrations were measured at regular intervals throughout the study. Isotopic GFR was determined at the end of the washout period and at week 24. Lacidipine was not very effective in controlling blood pressure and had an adverse effect on renal function. In 3 patients with an incipient nephrotic syndrome this necessitated withdrawal from the study. Mean GFR of the 10 patients who completed the study decreased from 0.69 ml/s/1.73 m2 at baseline to 0.56 ml/s/1.73 m2 at week 24 (p = 0.006) with a decline in GFR being observed in 9 of these patients. The decrease in GFR was greatest in patients with poorly controlled blood pressure. An insignificant increase in mean urinary albumin excretion occurred during the study with this increase being observed only in patients with albuminuria > 1 g/24 h at baseline. These findings indicated that systemic hypertension altered glomerular hemodynamics and that the vasodilatation of pre-glomerular vessels which followed introduction of the calcium antagonist may have exacerbated this situation. The withdrawal of an angiotensin converting enzyme inhibitor during the washout period may have contributed to these changes. We suggest that renal function should be monitored closely in patients with renal insufficiency when a calcium antagonist is being used to control blood pressure, particularly in those with either marginal blood pressure control, significant albuminuria or an incipient nephrotic syndrome.

Topics: Adult; Aged; Albuminuria; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; Furosemide; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Renal Insufficiency; Serum Albumin

The contributions of hypertension and diabetes to microvascular dysfunction in the kidney and eye were investigated. Two indices of microvascular dysfunction, urinary albumin excretion rate (AER) and albumin vascular clearance (AVC) in the eye, were studied in control and streptozocin diabetic Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).. Studies were performed on four groups of untreated rats--nondiabetic and diabetic WKY and nondiabetic and diabetic SHR--and on three groups of diabetic SHR treated with a converting enzyme inhibitor (perindopril), a calcium-channel blocker (lacidipine), or triple therapy (hydrochlorothiazide, reserpine, and hydralazine). In all rats, AER and AVC were measured at 16 weeks.. There was a progressive increase in both parameters in the order WKY, diabetic WKY, SHR, and diabetic SHR. When compared with nondiabetic WKY, diabetic SHR showed an approximately 30-fold increase in AER and an approximately threefold increase in AVC. Treatment of diabetic SHR with perindopril or triple therapy normalized AER compared to an equihypotensive dose of lacidipine, which had no effect. By contrast, the three antihypertensive regimens showed a different order of efficacy in preventing increases in ocular AVC. In diabetic SHR, the increase in retinal AVC was prevented largely by lacidipine, whereas the other two antihypertensive regimens showed lesser effects [AVC expressed as percentage nondiabetic WKY: untreated diabetic SHR 278% +/- 47%, lacidipine 93% +/- 10% (P < 0.001), triple therapy 132% +/- 37% (P < 0.05), and perindopril 167% +/- 9% (P < 0.05)]. Lacidipine also prevented the increase in AVC of the anterior and posterior uvea. By contrast, increases in AVC observed in the diabetic SHR were not prevented by perindopril in the posterior uvea or by triple therapy in the anterior uvea. Thus, hypertension and diabetes increased ocular AVC and AER, and effective antihypertensive therapy substantially prevented changes in both parameters. However, despite equivalent levels of blood pressure control for each regimen, discordant effects were noted on AVC and AER. Perindopril was associated with significantly lower AER than lacidipine, whereas lacidipine was more potent in preventing increases in ocular AVC.. Results of this study suggest that different antihypertensive regimens in the diabetic rat may exert organ-specific effects on the retina and kidney despite equivalent effects on systemic blood pressure. These data also raise the possibility that retinal microvascular dysfunction in diabetes is ameliorated more readily by calcium-channel blockade than by converting-enzyme inhibition, whereas the reverse applies to renal microvascular dysfunction, as reflected by albuminuria.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Capillary Permeability; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dihydropyridines; Drug Therapy, Combination; Hydralazine; Hydrochlorothiazide; Hypertension, Renal; Indoles; Kidney; Male; Organ Specificity; Perindopril; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reserpine; Retina; Serum Albumin

The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.

Topics: Albuminuria; Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Dihydropyridines; Disease Models, Animal; Hypertension; Indoles; Kidney Diseases; Male; Perindopril; Random Allocation; Rats; Rats, Inbred SHR; Renin

1. It has been suggested that hypertension may be an important determinant of the rate of progression of diabetic microangiopathy. 2. Renal microvascular disease as assessed by urinary albumin excretion and glomerular ultrastructure was evaluated in a model in which streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). 3. Diabetes was associated with increases in urinary albumin excretion, and hypertension resulted in a further increase in albuminuria. 4. Various antihypertensive regimens were administered to diabetic SHR, with the angiotensin-converting enzyme inhibitor perindopril and triple therapy (hydralazine, reserpine and hydrochlorothiazide) being more effective than the calcium antagonist (lacidipine) in retarding the increase in albuminuria in diabetic SHR. 5. Antihypertensive therapy appears to ameliorate the development of diabetic renal disease.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Nephropathies; Dihydropyridines; Hypertension, Renovascular; Indoles; Kidney Glomerulus; Male; Perindopril; Rats; Rats, Inbred SHR; Rats, Inbred WKY