Effects of captopril on renal function in hypertensive patients

Journal of Internal Medicine, 1994

Objectives. To study the importance of the reninangiotensin-I1 system for renal haemodynamics and sodium and water handling in the adapted remnant kidney in healthy uninephrectomized subjects. Design. Case-control study. Setting. All subjects were investigated at laboratory C, Department of Medicine and Nephrology, Skejby Hospital. Subjects. Fourteen healthy uninephrectomized (Unx) and 14 matched healthy control subjects (Cs). Intervention. Captopril, 2 5 mg orally. Main outcome measures. The glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using '251-iothalamate and 1311-hippuran as reference substances, tubular function was evaluated by the lithium clearance technique (CLi), urinary flow rate (V), sodium excretion (U,,V), fractional sodium excretion (FE,,), mean blood pressure (MBP) and heart rate (HR) were measured by conventional methods and plasma levels of angiotensin I1 (Ang-11), aldosterone (Aldo). arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were measured by radioimmunoassay. Results. In both groups captopril ingestion resulted in a significant decrease in the MBP (Unx: 87.1 to 83.5 and Cs: 86.8 to 83.8 mmHg, median values), filtration fraction (Unx: 24.6 to 22.1 and Cs: 24.1 to 22.5%, median values) and Ang-Ll (Unx: 10.5 to 7.7 and Cs: 12 to 7.6 pmol-', median values). Single kidney GFR, V, and C,, were unchanged in both groups. FEN, and single kidney RPF were significantly increased in only the Cs group: F E N , (Unx: 1.81 to 1.91 and Cs: 1.56 and 1.90% median values). The plasma level of ANP was significantly decreased in only the Unx group. Conclusion. The data suggest that sodium handling in the remnant kidney in uninephrectomized subjects could be less sensitive to Ang-I1 than in healthy control subjects, and that this might be as a result of adaptive changes in the distal parts of the nephron.

European Journal of Clinical Investigation, 1981

The effects of Captopril on blood pressure and renal function were evaluated in ten patients with different degrees of hypertension. In seven, blood pressure was reduced after 7 weeks of therapy; in three it remained practically unchanged. No correlation was found between the standing plasma renin activity before treatment and the hypotensive response. Plasma renin activity increased significantly from the median value of 5.4 (range 1-16.7) to 9.5 (range 2.6-19.8) ng ml-' h-' (P<O.O5) and urine aldosterone significantly fell from 13 (range 2.3-52.5) to 7.4 (range 1.614) pg 24 h-' (P<O.OI) during therapy. Renal plasma flow decreased from 534 (range 300-616) to 471 (range 333-606) ml min-I, but the difference was not significant, and glomerular filtration rate fell significantly form 122 (range 64-143) to 88 (range 71-1 16) ml min-' (P<O.O5). N o urinary excretion of alpha?-macroglobulin was observed during Captopril. 24 h proteinuria, albumin and transferrin clearance, alanine-amino transferase, gammaglutamyl transferase and alpha glucosidase excretion rate and malatedehydrogenase clearance remained unaltered throughout the treatment. This indicates that neither glomerular permeability nor renal tubular function were affected by the drug.

Clinics, 2010

2000

In this study we investigated the short-term effects of calcium channel blockers and angiotensin-converting enzyme inhibitors on renal hemodynamics and the urinary excretion of proteins with different relative mass in subjects with mild to moderate essential hypertension and apparently normal glomerular filtration rate but reduced renal functional reserve. Sixteen subjects underwent the following four treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral nifedipine (20 mg), and (4) high-protein meal plus oral captopril (50 mg). Two urine samples were obtained after meals. Blood samples were drawn at the midpoint of each 120-minute urine collection period. Urine and serum were tested for total protein, immunoglobulin G, albumin, a r microglobulin, retinol binding protein, and /3 2 -microglobulin. Glomerular filtration rate and renal plasma flow were assessed by iothalamate and p-aminohippuric clearance, respectively. Compared with the high-protein meal alone, nifedipine elicited a clear-cut increase in the urinary excretion of total protein (+60%, F<.01), immunoglobulin G (+58%, P<.01), albumin (+25%, P<.05), retinol binding protein (+47%, P<.05), and ft-microglobulin (+52%, P<.05); captopril decreased the urinary excretion rate of immunoglobulin G (-26%, P<.05), albumin (-22%, P<.05), and /3 r microglobulin (-34%, P<.05). The ratio between the clearances of immunoglobulin G and albumin was higher after nifedipine (+21%, P<.0l) and unchanged after captopril (-9%, P=NS) compared with the high-protein meal alone. Glomerular filtration rate and renal plasma flow were higher after nifedipine (+10%, P<.05 and +9%, P<.05, respectively) and lower after captopril (-2%, P<.05 and -9%, / ) =NS, respectively) than after the high-protein meal alone. Thus, single doses of nifedipine, preceding a protein load in the form of a meat meal, raise both glomerular filtration rate and renal plasma flow and increase urinary protein excretion rate. Changes in both glomerular selectivity and tubular reabsorption seem to account for increased proteinuria. (Hypertension. 1994;24:763-769.)

1984

Elimination kinetics of captopril in patients with renal failure. Captopril kinetics were determined after a 100-mg oral dose of 4C-captopril in 21 patients with various degrees of renal impairment. Elimination kinetics of captopril were evaluated by model-independent methods. The body clearance (CIB) of captopril decreased steadily with decreasing creatinine clearance (Clr) from 5.2 mI/mm/kg for mild renal failure patients to 1.6 mI/mm/kg for hemodialysis patients during an interdialytic period. In patients with mild renal impairment, renal and nonrenal clearances of captopril averaged 2.2 and 3.0 mI/mm/kg, respectively, and fell (P < 0.001) to 0.2 and 1.5 mI/mm/kg in patients with severe renal impairment. There were no significant differences in the extent of total cumulative excretion (fecal plus urinary) of radioactivity over a 96to 120-hr period between the patients with mild, moderate, and severe renal impairment. The 48-hr renal excretion of captopril averaged 29. 21, and 8% of the dose in the mild, moderate, and severe renally impaired groups. In five additional hemodialysis patients, the mean dialyzer clearance of captopril averaged 120 mI/mm. Approximately 35% of the dose was recovered in the 4-hr dialysate. Based on the above findings, a reduction in the dose of captopril is necessary in patients with renal failure. Cinetique d'élimination du captopril chez les malades en insuffisance rénale. La cinetique du captopril a été déterminée après une dose orale de 100 mg de '4C-captopril chez 21 malades atteints d'insuffisance rénale a des degres divers. La cinétique d'élimination du captopril a éte évaluée par des méthodes indépendants du modéle. La clearance corporelle (CIB) du captopril diminuait progressivement avec Ia baisse de Ia clearance de Ia créatinine (Clr) de 5,2 mg/mm/kg chez les malades en insuffisance rénale modérée a 1,6 mi/mm/kg chez les malades en hemodialyse lors d'une période interdialytique. Chez les malades en insuflisance rénale modérée, les clearances rénales et non rénales du captopril étaient en moyenne de 2,2 et 3,0 mI/mm/kg, respectivement, et chutaient (P < 0,001) a 0,2 et 1,5 mI/mm/kg chez les malades avec une alteration rénale sévére. II n'y avait pas de differences significatives dans l'importance de l'excrétion cumulative totale (fécale et urinaire) de radloactivité sur une période de 96 a 120 heures entre les malades atteints d'une alteration rénale modérée, moyenne ou sévère. L'excrétion rénale de 48 heures du captopril Ctait en moyenne 29, 21, et 8% de Ia dose dans les groupes avec des alterations rénales modérCes, moyennes ou sévéres. Chez cinq malades hémodialysés supplementaires, Ia clearance dialytique moyenne du captopril était de 120 mI/mm. Environ 35% de Ia dose était retrouvee dans un dialysat de 4 heures. D'après ces résultats, une diminution de Ia dose de captopril est nécessaire chez les malades en insuffisance rénale.

American Journal of Kidney Diseases, 1992

• Glomerular hyperfiltration and hypertension induced by extensive loss of renal parenchyma are suspected to accelerate progression of renal failure. Amino acid infusion or protein ingestion also modify renal hemodynamics and increase glomerular filtration rate (GFR). This phenomenon was used to study the influence of two commonly used antihypertensive agents, captopril and nifedipine, on renal hemodynamics at rest and during glomerular hyperfiltration. Thirteen healthy volunteers were studied on three separate days (days A, B, and C) in random sequence: inulin and p-amino hippurate (PAH) clearance were measured first under glucose infusion and afterwards under stimulation by amino acid infusion (0.35 mmol/kg/min; 4 mg/kg/min). Day A served as a control, where no medication was given. On day B, 10 mg nifedipine, and on day C, 25 mg captopril, were administered orally before study. Without premedication (= day A, control) GFR increased from 108.0 ± 6.9 mL/min (SEM)to 131.7 ± 7.0 mL/min (P < 0.05). On day B(nifedipine), GFR before stimulation by amino acids was already elevated to 121.8 ± 4.2 mL/min (P < 0.05 compared with day A) and increased to 132.6 ± 6.3 mL/min with infusion of amino acids, thus to the same range as on day A without medication. On day C, after captopril, GFR did not increase with infusion of amino acids (from 112.5 ± 7.2 to 117.3 ± 6.3 mL/min). Our results indicate the calcium channel antagonist nifedipine and the angiotensin-converting enzyme (ACE) inhibitor captopril differ in their effect on intrarenal hemodynamic parameters. Nifedipine induces hyperfiltration at rest and allows maximal hyperfiltration to develop under amino acid infusion. In contrast, captopril prevents amino acid-induced glomerular hyperfiltration. Since modification of intrarenal hemodynamics supposedly delays the progression of renal insufficiency, blunting of diet-induced glomerular hyperfiltration by ACE inhibitors could contribute to their protective effects on the failing kidney.

European Journal of Clinical Pharmacology, 1993

British Journal of Clinical Pharmacology, 1984

The pharmacokinetic parameters of unchanged plasma captopril and the kinetics of the drug effects on plasma converting enzyme activity (PCEA), plasma renin activity (PRA), plasma aldosterone (PA) and mean blood pressure (MBP) were studied over 24 h after oral administration in three groups of hypertensive patients: with normal renal function (group 1, plasma creatinine < 110 pumolIl, n = 10), with moderate chronic renal failure (group 2, 135 < plasma creatinine < 450 pumolIl, n = 10) and with severe chronic renal failure (group 3, plasma creatinine > 500 ,umol/l, n = 10). 2 Renal impairment had no effect on plasma captopril Cmax, CLtot and relative bioavailability (AUC). In contrast, captopril kei decreased while T,/2 increased progressively from group 1 to group 3. 3 PCEA blockade (T,/2 and AUC) was increased significantly and proportionally to the degree of renal impairment. However, there were no differences between the three groups regarding captopril-induced modifications of PRA and PA. 4 Although the maximal reduction in MBP was identical in the three groups, the overall antihypertensive effect (AUC) of captopril increased significantly and progressively from group 1 to group 3, especially in duration. 5 There was no correlation between basal plasma creatinine values and unchanged captopril relative bioavailability (AUC) and between unchanged captopril relative bioavailability (AUC) and the drug effects (AUC) on PCEA, PRA, PA and MBP. However there was a correlation between basal plasma creatinine values and plasma captopril TI,, PCEA blockade (AUC) and overall antihypertensive effect (AUC). 6 The apparent discrepancy between the lack of effects of chronic renal failure on plasma unchanged captopril bioavailability and its potentiating effects on PCEA blockade and MBP reduction may be accounted for by the renal impairment-induced accumulation of captopril metabolites.

Journal of Nuclear Medicine

context, a noninvasive test that could detect functionally significant renal artery stenosis and identify beneficial or detrimental renal effect of ACE inhibitors in kidney failure wouldbe very useful.

Clinical science. Supplement (1979), 1982

activity of the renin-angiotensin system L2-41. 1. Systemic, humoral and renal responses to isotonic volume expansion (1800 ml in 3 h) were assessed in normal subjects and patients with normal renin essential hypertension before and during captopril administration. 2. Essential hypertensive subjects had a greater natriuretic and diuretic response to volume expansion than had normotensive subjects. 3. Captopril induced a fall in pre-saline mean arterial pressure more marked in hypertensive (20 f 3 mmHg) than in normotensive subjects (9 f 2 mmHg) and did not produce any change in sodium balance. 4. Captopril exaggerated the response of arterial pressure to volume expansion since mean arterial pressure increased more markedly after than before captopril in both normotensive (18.7 k 3.8%) and hypertensive subjects (16.9 f 3-7%). 5. Captopril blunted the exaggerated natriuretic response to volume expansion observed in patients with essential hypertension, whereas the renal response was unchanged in normotensive subjects.