Effect of lacidipine, a dihydropyridine calcium antagonist on renal function of hypertensive patients with renal insufficiency.

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.