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PubMed2002

Podocytopenia and disease severity in IgA nephropathy.

BACKGROUND: IgA nephropathy is a common form of progressive glomerular disease, associated with proliferation of mesangial cells and mesangial deposition of IgA. The present study was designed to investigate functional and morphological covariates of disease severity in patients with IgA nephropathy. METHODS: Glomerular hemodynamics, permselectivity and ultrastructure were studied in 17 adult patients with IgA nephropathy using inulin, para-aminohippuric acid (PAH) and 3H-Ficoll clearances and morphometric methods. A mathematical model of macromolecule permeation through a heteroporous membrane was used to characterize glomerular permselectivity. Controls consisted of 14 healthy living kidney donors and 12 healthy volunteers. RESULTS: The patients were heterogeneous in their disease severity, but as a group had a decreased glomerular filtration rate (GFR) and increased urinary protein excretion compared to controls [63 +/- 29 SD vs. 104 +/- 23 mL/min/1.73 m2, P < 0.001, and (median) 1.34 vs. 0.11 g/day, P < 0.0001, respectively). A multivariate analysis of structural and functional relationships revealed GFR depression to be most strongly correlated with the prevalence of global glomerular sclerosis (t = -4.073, P = 0.002). Those patients with the most severe glomerular dysfunction had a reduced number of glomerular visceral epithelial cells (podocytes) per glomerulus. The degree of podocytopenia was related to the extent of glomerular sclerosis and of impairment of permselectivity and GFR, with worsening injury below an apparent threshold podocyte number of about 250 cells per glomerulus. There were no corresponding correlations between these indices of injury and the number of mesangial and endothelial cells. CONCLUSIONS: Our findings show that podocyte loss is a concomitant of increasing disease severity in IgA nephropathy. This suggests that podocyte loss may either cause or contribute to the progressive proteinuria, glomerular sclerosis and filtration failure seen in this disorder.

Adult↗
PubMed2002

Dynamic renal blood flow measurement by positron emission tomography in patients with CRF.

BACKGROUND: Positron emission tomography (PET) is a functional imaging device that allows dynamic regional blood flow measurements. We performed a study to test whether PET could detect acute changes in renal blood flow (RBF) in patients with chronic renal failure (CRF). METHODS: RBF was measured by means of PET (PET-RBF) using oxygen 15-labeled water (H2(15)O) in eight men with hypertension and moderate CRF before and 5, 40, 80, and 120 minutes after the injection of quinaprilat (10 mg intravenously). Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured simultaneously by para-aminohippuric acid (PAH-ERPF) and inulin clearances before and 20, 60, 100, and 140 minutes after quinaprilat injection. RESULTS: Baseline RBF and ERPF were decreased in all patients (221 +/- 20 mL/min/100 g and 225 +/- 38 mL/min/1.73 m2, respectively). PET-RBF increased significantly after quinaprilat injection (+15%, +26%, +19%, and +23% versus baseline; P < 0.003). PAH-ERPF did not increase significantly (-6%, +12%, +20%, and +15% versus baseline; P = 0.15). GFR (50.1 +/- 8.9 mL/min/1.73 m2 at baseline) did not change significantly after quinaprilat injection; however, filtration fraction (GFR-ERPF ratio) decreased significantly from 0.23% +/- 0.02% to 0.20% +/- 0.02% (P = 0.0004). Mean arterial pressure decreased significantly after quinaprilat injection (P < 0.005). CONCLUSION: This study dynamically measured RBF by means of PET in patients with CRF for the first time. It showed that RBF rapidly increased after quinaprilat injection. PET using H2(15)O is a powerful method for the noninvasive measurement of dynamic changes in RBF that remain undetected by PAH clearance.

Adolescent↗
PubMed1991

Renal hemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with hypertensive and normotensive parents.

BACKGROUND AND METHODS: The kidney is important in blood-pressure regulation, but its role in the development of essential hypertension is still subject to debate. We compared renal hemodynamics, measured in terms of the clearance of para-aminohippuric acid and inulin, and the characteristics of the renin-angiotensin-aldosterone system in three groups of normotensive subjects at different degrees of risk for hypertension: 41 subjects with two normotensive parents, 52 with one normotensive and one hypertensive parent, and 61 with two hypertensive parents. The subjects ranged in age from 7 to 32 years. RESULTS: The mean renal blood flow was lower in the subjects with two hypertensive parents than in those with two normotensive parents (mean difference [+/- SE], 198 +/- 61 ml per minute per 1.73 m2 of body-surface area; P = 0.002). Moreover, both the filtration fraction and renal vascular resistance were higher in the subjects with two hypertensive parents (filtration fraction: mean difference, 3.0 +/- 1.1 percentage points; P = 0.006; renal vascular resistance: mean difference, 2.7 +/- 0.8 mm Hg per deciliter per minute per 1.73 m2; P = 0.006). The subjects with two hypertensive parents had lower plasma concentrations of renin (mean difference, 3.3 +/- 1.6 mU per liter; P = 0.03) and aldosterone (mean difference, 111 +/- 36 pmol per liter; P = 0.003) than those with two normotensive parents. The differences could not be explained by the small differences in blood pressure between the groups. The values in the subjects with one hypertensive and one normotensive parent fell between those for the other two groups. CONCLUSIONS: Renal vasoconstriction is increased and renin and aldosterone secretion is decreased in young persons at risk for hypertension. These findings support the hypothesis that alterations in renal hemodynamics occur at an early stage in the development of familial hypertension.

Adolescent↗
PubMedDate not supplied

Effects of drugs which influence renal transport systems on the urinary excretion of the beta 2-adrenoceptor agonist clenbuterol and the anabolic steroids ethinylestradiol and methyltestosterone.

The aim of this study was to determine whether the illegal application of clenbuterol, ethinylestradiol and methyltestosterone in cattle as growth promoters can be concealed by co-treatment with drugs that affect urinary excretion. Six male veal calves were fed with 0.8 micrograms clenbuterol kg-1 of body weight (BW), 3.5 micrograms ethinylestradiol kg-1 BW and 35 micrograms methyltestosterone kg-1 BW together twice daily for 28 days. At the eighth day of clenbuterol, ethinylestradiol and methyltestosterone treatment each calf was additionally fed either with probenecid, para-aminohippuric acid, trimethoprim, famotidine or cimetidine at three different doses which were increased in weekly intervals. During the treatment 24 h-urine and blood samples (once daily) were obtained and analysed for clenbuterol, ethinylestradiol and methyltestosterone by specific enzyme immunoassay. By high performance liquid chromatography/enzyme immunoassay it was determined whether these drugs or their metabolites interfered with the immunological detection of the growth promoters. Clenbuterol, ethinylestradiol and methyltestosterone could be detected in plasma and urine throughout the whole experiment. Co-treatment with probenecid led to a five-fold reduction in urinary excretion of ethinylestradiol and co-treatment with trimethoprim led to a three-fold reduction in urinary excretion of clenbuterol. None of the drugs reduced urinary excretion of the growth promoters to concentrations below the limit of detection. The detection of these three growth promoters in urine samples from calves which were co-treated with the drugs tested in this study can thus not be prevented.

Adrenergic beta-Agonists↗
PubMed2001

Sodium and water homeostasis in children with shigellosis.

UNLABELLED: Studies in Bangladesh have shown that the mortality in shigellosis is significantly higher in hyponatraemic (HN) than in normo- (NN) or hypernatraemic children. The aim of this study was to describe the effect of shigellosis on renal haemodynamics and sodium and water homeostasis before treatment was started. Twenty-one moderately ill children infected with Shigella dysenteriae type I were studied. Eight of them had a serum sodium concentration below 130 mmol/L. Renal function was determined by glomerular filtration rate measured by clearances of inulin and iohexol. Effective renal plasma flow was estimated by clearance of para-aminohippuric acid. Plasma renin, aldosterone and anti-diuretic hormone were also studied. The HN children had significantly higher haemoglobin and haematocrit levels than the NN group. There was an inverse correlation between serum sodium and haemoglobin, and a direct correlation between serum sodium and urinary sodium and urinary chloride. Direct correlations were found between serum aldosterone and haemoglobin, plasma renin and systolic blood pressure and an inverse correlation between serum aldosterone and serum sodium. Clearances of inulin and iohexol were normal. Detectable levels of ADH were found in both groups, despite low serum osmolalities. CONCLUSION: The HN state seems to be triggered by multiple factors. The normal glomerular filtration rate excludes a volume expansion secondary to reduced renal function. Inappropriate or a physiological increase of anti-diuretic hormone secretion may be of importance. The higher sodium losses in stools of the HN children might also be a factor contributing to the HN.

Body Mass Index↗
PubMed2005

In vivo evidence for the efflux transport of pentazocine from the brain across the blood-brain barrier using the brain efflux index method.

The efflux transport of pentazocine (PTZ) from the brain across the blood-brain barrier (BBB) was investigated using the Brain Efflux Index method. PTZ was eliminated with the apparent elimination half-life of 13.0 min after microinjection into the parietal cortex area 2 region of the rat brain. The apparent efflux clearance of PTZ across the BBB was 137 microl/min/g brain, which was calculated from the elimination rate constant (5.35 x 10(-2) min(-1) and the distribution volume in the brain (2.56 ml/g brain). The efflux transport of PTZ was decreased in the presence of unlabeled PTZ, suggesting that PTZ is eliminated by a carrier-mediated transport system across the BBB. To characterize the efflux transport of PTZ from the brain in vivo, the effects of several compounds on the efflux transport of PTZ were investigated. P-glycoprotein (P-gp) inhibitors (verapamil and quinidine) reduced the PTZ efflux transport. In addition, the efflux transport of PTZ was inhibited by organic cations such as l-carnitine and tetraethylammonium (TEA), whereas organic anions such as p-aminohippuric acid, probenecid and taurocholate did not affect the PTZ efflux transport. The present results suggest that PTZ is transported from the brain across the BBB via l-carnitine/TEA-sensitive carrier-mediated efflux transport system(s) in addition to P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

An ESR contrast agent is transported to rat liver through organic anion transporter.

Carboxy PROXYL is a useful extracellular paramagnetic contrast reagent in electron spin resonance (ESR) and magnetic resonance imaging (MRI). Active transfer of the probe was investigated using an in situ liver model in rats. Carboxy PROXYL, a nitroxyl spin probe, was perfused into in situ liver perfusion system from Wistar rats. Concentration of nitroxyl form of the spin probe in effluent increased gradually after introducing perfusate with the spin probe and reached a plateau. The disappearance of Carboxy PROXYL from the perfusate was 40%, which could not be explained with its partition coefficient. Administration of non-selective inhibitors of organic anion transporters, p-aminohippuric acid and penicillin G, inhibited competitively and in a dose dependent manner the transfer of Carboxy PROXYL into rat liver in situ, resulting in increases of Carboxy PROXYL in the effluent. The results demonstrate that there is an active transfer system of an ESR contrast reagent into in situ rat liver through organic anion transporters.

Animals↗
PubMed1958

Renal tubular transport of inorganic divalent ions by the aglomerular marine teleost, Lophius americanus.

A characterization was attempted of the mechanisms involved in the tubular transport of inorganic divalent ions by the aglomerular kidney of Lophius, attention being paid particularly to the possible existence of transport maxima (Tm) and to competition for transport among related substances undergoing tubular excretion. Excretory rates of divalent ions in non-treated fish during standard laboratory conditions paralleled spontaneous changes in urine flow. Tm rates of excretion were reached for magnesium, sulfate, and thiosulfate with corresponding plasma levels of 2 to 5, 5 to 17, and 4 to 12 microM/ml. respectively. Elevation of magnesium chloride levels in plasma markedly depressed calcium excretion; sodium thiosulfate similarly depressed sulfate excretion. Experimental observations suggest the existence of a transport system for divalent cations separate from another for divalent anions. Within each transport system the ion with the higher excretion rate depressed competitively transfer of the other ion. Neither system was influenced by probenecid (benemid) in doses which markedly depressed the simultaneous excretion rate of p-aminohippuric acid.

Animals↗
PubMed1982

Sex-related differences in the susceptibility of rats to gentamicin nephrotoxicity.

Age-matched male and female Fischer 344 rats were treated with gentamicin, 40 mg/kg of animal body weight per day, for three to 21 days. Renal dysfunction was less severe in females as measured by concentrations of blood urea nitrogen and creatinine and by cortical slice uptake of p-aminohippuric acid and N1-methylnicotinamide chloride. Also, cortical concentrations of gentamicin in females were lower than in males. Neither exogenous testosterone administered to adult females nor castration of prepubertal males changed the pattern of dysfunction. These results show that sex affects susceptibility to aminoglycoside nephrotoxicity by mechanisms that are undefined but that are apparently unrelated to testosterone. The variable of sex needs to be considered in interpreting the results of studies of experimental aminoglycoside nephrotoxicity.

Animals↗
PubMed1980

Glucose and lactate absorption and metabolic interrelationships in lambs switched from low to high concentrate diets.

Two experiments were conducted to measure glucose and lactate absorption and metabolic interrelationships in lambs either switched gradually (experiment 1) or abruptly (experiment 2) from hay to a high concentrate diet. In experiment 1, seven lambs were given primed, continuous, 3-hour infusions of 2-0[3H]glucose, U-[14C]L-lactate and para-aminohippuric acid (portal blood flow indicator) before and after switching from a pelleted hay to a pelleted, 85% concentrate diet. Blood samples were collected at 20-minute intervals during infusions. In experiment 2, four lambs were abruptly switched from a pelleted hay to an all-concentrate diet. Portal and arterial blood samples were collected before and up to 1 week after the diet switch. As a result of increased concentrate intake (experiment 1) net portal absorption and turnover of L-lactate and glucose increased. Percentage of glucose derived from L-lactate decreased. Net portal D-lactate absorption, L-lactate absorption as a percentage of turnover and conversion of L-lactate to glucose were not affected by diet. Lambs in experiment 2 did not become acutely acidotic. The insult to acid-base status peaked 12-16 hours after the diet switch, concurrent with maximum arterio-venous differences in plasma L-lactate and glucose. Arterio venous differences in plasma D-lactate were not significantly affected.

Absorption↗
PubMed1981

Glucose and lactate absorption and metabolic interrelationships in steers changed from low to high concentrate diets.

Cannulas were surgically implanted in the portal and mesenteric veins and femoral artery of eight crossbred steers averaging 270 kg. They were given primed, continuous 3-hour infusions of U-[14C]-L-lactate and 2-[3H]- or 6-[3H]-glucose into the jugular vein and para-aminohippuric acid (portal blood flow indicator) into the mesenteric vein before and after being changed from a pelleted alfalfa hay to a pelleted 85% concentrate diet. Blood samples were collected at 20-minute intervals during infusions. Reliable blood flow data were obtained on four of the eight steers during the first infusion; the other four were not infused the second time. Dry matter intake, portal blood flow, net portal D-lactate absorption (P less than 0.10), net portal glucose absorption and L-lactate turnover rate (P less than 0.10) increased as a result of increased concentrate (energy) intake. Glucose turnover rate (P less than 0.10), L-lactate absorbed as a percentage of turnover rate, L-lactate converted to glucose and glucose derived from L-lactate concomitantly decreased. Net portal L-lactate absorption was not affected. The direction of the response for portal blood flow, net portal D-lactate absorption, net portal glucose absorption, L-lactate turnover and L-lactate absorbed as a percentage of turnover was the same as that previously observed in lambs under similar experimental protocol. Differences in responses between lambs and steers for glucose turnover and L-lactate converted to glucose may be attributable to differences in dry matter or energy intake or both.

Absorption↗
PubMed1986

Glucose absorption and hepatic gluconeogenesis in dairy cows fed diets varying in forage content.

One dry and four lactating Holstein cows were prepared with chronic catheters in the mesenteric, hepatic and portal veins and used to study glucose absorption and hepatic gluconeogenesis. The dry cow was used in a preliminary assessment of the methods. In the main experiment high concentrate and high forage diets, providing equal energy intake, were delivered in hourly portions from an automatic feeder as total mixed rations. A few data were collected with the high concentrate ration fed ad libitum in early lactation. A few additional observations were made with limited feed intake by using the same cows subsequent to the main experiment. Portal and hepatic vein blood flow rates were determined by using para-aminohippuric acid. Glucose entry rates were significantly higher during ad libitum feeding of the high concentrate diet than during feeding of the two diets with restricted intake. There was no difference between high concentrate and high forage diets when fed at equal energy intakes. Net glucose appearance in portal blood was demonstrated. Data from this study and from the literature were used to develop general relationships between digestible energy intake and 1) portal vein blood flow, 2) rate of portal appearance of glucose and 3) total splanchnic glucose entry rate.

Absorption↗
PubMed1997

Is endogenous erythropoietin a pathogenetic factor in the development of essential hypertension?

BACKGROUND: Recent experimental studies have found that erythropoietin elicits vasoconstriction and proliferation of endothelial cells. We conducted the following study to assess the possible interactions between endogenous erythropoietin, systemic and renal haemodynamics at different stages of essential hypertension. METHODS: We examined 47 patients with borderline essential hypertension (age 26 +/- 3 years) and 49 patients with established essential hypertension WHO stage I-II (age 52 +/- 10 years), and compared them to 42 normotensive individuals (age 26 +/- 3 years). The concentration of erythropoietin (radioimmunoassay), 24-h ambulatory blood pressure (Spacelab 90207), systemic haemodynamics (Doppler sonography) and renal haemodynamics (para-aminohippuric acid and inulin clearance) were determined. RESULTS: Erythropoietin was within normal range and similar among the three groups. In patients with established essential hypertension, a close correlation was found between erythropoietin and systolic (r = 0.45, P < 0.002) and diastolic (r = 0.51, P < 0.001) ambulatory blood pressure. In contrast, ambulatory blood pressure was not correlated with erythropoietin in subjects with borderline hypertension. Total peripheral resistance (r = 0.41, P < 0.02) was linked to erythropoietin in established but not in borderline hypertension. However, erythropoietin was inversely correlated with renal plasma flow in both established and borderline hypertension (r = -0.33, P < 0.05, and r = -0.34, P < 0.05 respectively). In normotensive subjects, in contrast, erythropoietin was not correlated with any of the determined variables. In neither group erythropoietin was linked to the haematocrit or hemoglobin concentration. CONCLUSION: The correlation between erythropoietin and renal vascular changes which is already present in borderline hypertension and is confirmed in established hypertension indicates an involvement of erythropoietin in the development of essential hypertension. The presence of normal concentrations of endogenous erythropoietin in all groups suggests a dysregulation of erythropoietin in patients with essential hypertension as the pathophysiological link between erythropoietin and vascular changes.

Adult↗
PubMed2000

Renal function of children exposed to cyclosporin in utero.

BACKGROUND: The use of cyclosporin (CsA) has improved graft survival in transplant (Tx) patients despite its potential nephrotoxicity. Children born to transplanted women may present with intrauterine growth retardation (IUGR). On the basis of potential reduced nephron mass both in IUGR and in newborn experimental animals exposed to CsA in utero, we investigated the renal function of children >1 year of age born to women under maintenance immunosuppression, including CsA. METHODS: Fourteen children born to 12 Tx women (nine kidney, one pancreas-kidney, one heart, one liver) were investigated using inulin clearance (C(in)), para-aminohippuric acid clearance (C(PAH)), microalbuminuria, and electrolyte reabsorption rate. RESULTS: Gestational age of the 14 infants was 34+/-3 weeks and birth weight 2018+/-620 g. During pregnancy, CsA trough blood level was 234+/-115 microg/l and plasma creatinine range was 96-136 micromol/l. Two children were excluded from the study because renal investigation led to a diagnosis of hereditary nephritis (one Alport syndrome, one familial dominant focal segmental glomerulosclerosis) that was retrospectively completed in the mother. Renal function tests were finally performed in 12 children at 2.6+/-1.8 years of age: BP 94+/-7/55+/-5 mmHg, C(in) 117+/-28 ml/min/1.73 m(2), C(PAH) 545+/-124 ml/min/1.73 m(2), filtration fraction 0.23+/-0.03, microalbuminuria 4.2+/-3.5 mg/mmol. Electrolyte tubular reabsorption rates and urine concentrating capacity were normal. CONCLUSION: These results suggest that in children born to transplanted women taking CsA, renal function develops normally despite prolonged exposure in utero.

Child↗
PubMed2001

Erythropoietin enhances recovery after cisplatin-induced acute renal failure in the rat.

BACKGROUND: Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not only of erythroid progenitor cells but also of certain other cell types. We attempted to establish whether Epo enhances the recovery from acute renal failure induced by cisplatin. METHODS: Sprague-Dawley rats were randomized into three groups. In the cisplatin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group, animals received intrapertoneal cisplatin and a daily injection of Epo (100 IU/kg) for 9 days. In the control group, animals received both placebo preparations alone. Para-aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate. In addition, light microscopy and immunohistochemistry examinations were performed, and in situ proliferating cell nuclear antigen (PCNA) staining was done to estimate the degree of renal tubular cell regenerative activity. The potential role of epithelial growth factor (EGF) was evaluated by semi-quantitative assessment of EGF immunostaining. RESULTS: Renal blood flow and glomerular filtration rate decreased significantly in cisplatin and cisplatin+Epo groups versus control group at day 4. However, at day 9, they both were significantly greater in cisplatin+Epo-treated animals than in rats that had received cisplatin alone. Tubular cell regeneration was significantly enhanced at day 4 in cisplatin+Epo group, compared with cisplatin and control groups respectively. EGF immunostaining was not significantly different between the three groups. CONCLUSION: Epo significantly enhanced the rate of recovery from acute renal failure induced by cisplatin. PCNA staining indicated that Epo might act directly via stimulation of tubular cell regeneration.

Acute Kidney Injury↗
PubMed1994

Misoprostol in renal transplant recipients: a prospective, randomized, controlled study on the prevention of acute rejection episodes and cyclosporin A nephrotoxicity.

The aim of this prospective and randomized study was to determine whether misoprostol, an analogue of PGE1, could decrease the incidence and the number of rejection episodes and could improve the renal function over a 12-month follow-up, when given at 400 micrograms/day for 12 months in renal transplant patients. Given the known side-effects and the additive cost of misoprostol, a benefit of the therapy should be a decrease of at least 50% in the incidence of rejection episodes in the treated group. Therefore, 60 consecutive renal transplant patients were randomized to receive misoprostol or to receive aluminium and magnesium hydroxide. Patients received steroids, azathioprine, antithymocyte globulins, and cyclosporin A (CsA). CsA was randomly started on day 0 or on day 8. At 12 months, no difference in the incidence of rejection episodes was observed: 63.3% in the 30 patients of the misoprostol + group versus 70.0% in the misoprostol-group (P = 0.558 Mantel-Cox). The renal function, assessed by plasma creatinine, inulin, and para-aminohippuric acid clearances, was not significantly different between misoprostol + and misoprostol-groups. No episode of CsA nephrotoxicity was observed in any patient of group one or group two. At 12 months, the mean dosage of CsA was 4.9 +/- 0.28 mg/kg/day in the misoprostol + group versus 4.52 +/- 0.23 mg/kg/day in the misoprostol-group and the trough level was not significantly different between the two groups. The graft survival rate at 12 months was 86.7% in the Misoprostol + group and 83.33% in the misoprostol-group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1996

Renal effects of captopril, indomethacin and nifedipine in nephrotic patients after an oral protein load.

BACKGROUND: In this study we investigated whether the increase in proteinuria induced by an oral protein load may be prevented by the angiotensin-converting enzyme inhibitor (ACEI) captopril in patients with nephrotic syndrome, and whether the effects of captopril on renal haemodynamics and/or glomerular selectivity are comparable to those obtained with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin and the calcium-channel blocker (CaCB) nifedipine. METHODS: Twelve subjects underwent the following 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 captopril (50 mg), (4) high-protein meal plus oral nifedipine (10 mg), (5) high-protein meal plus oral indomethacin (50 mg). Urine and blood samples were obtained after meals and tested for total protein, immunoglobulin G and albumin. GFR and renal plasma flow (RPF) were calculated from iothalamate and p-aminohippuric acid clearances respectively. RESULTS: Mean arterial pressure decreased significantly after both captopril (-4%, P = 0.001) and nifedipine (-5%, P = 0.0019). Compared with the low-protein meal, mean values of GFR and RPF increased significantly after the high-protein meal alone (+21%, P = 0.0002; +10%, P = 0.0491 respectively), and after captopril (+18%, P = 0.0025; +24%, P = 0.0034 respectively) or nifedipine administration (+30%, P = 0.0001; +21%, P = 0.0036 respectively), whereas they remained unchanged after the high-protein meal plus indomethacin administration. FF did not change significantly under the five experimental conditions. The increase in urinary protein excretion induced by the meat load (total protein +18%, P = 0.0102; albumin +26%, P = 0.0316; IgG +28%, P = 0.0203) was entirely blocked by both captopril and indomethacin, whereas it was further increased by nifedipine administration. CONCLUSIONS: Both captopril and indomethacin, but not nifedipine, are able to prevent the increase in urinary protein excretion rate following a meat meal. The antiproteinuric effect of captopril is comparable to that of indomethacin, but the renal haemodynamic changes induced by these drugs differ considerably, because the filtration capacity and the renal functional reserve were preserved by captopril and decreased by indomethacin. The reduction in systemic blood pressure following administration of both captopril and nifedipine does not account for changes in proteinuria, since, with a similar degree of blood pressure lowering, urinary protein excretion is reduced by captopril and increased by nifedipine.

Adolescent↗