Effects of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis

Acute intravenous amino acid infusion or a high-protein diet increases renal plasma flow and the glomerular filtration rate in healthy subjects. Conversely, a low-protein diet reduces renal plasma flow and glomerular filtration rate. The aim of this study was to investigate the effect of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis. Protocol 1: renal plasma flow and glomerular filtration rate were measured before and during intravenous administration of a 10% amino acid solution (0.043 ml/kg/min) to eight compensated cirrhotic patients (group 1), nine nonazotemic cirrhotic patients with ascites (group 2) and seven cirrhotic patients with ascites and functional renal failure (group 3). Amino acid administration induced a significant increase in renal plasma flow and glomerular filtration rate in all groups studied. Renal plasma flow and glomerular filtration rate increased by 16% and 14%, respectively, in group 1; 31% and 22% in group 2 and 25% and 21% in group 3. Protocol 2: Renal plasma flow and glomerular filtration rate were measured in nine cirrhotic patients with ascites after 11 days on a low-protein diet (0.5 gm/kg body weight/day) and also after the patients followed for 11 days a moderately high-protein diet (1.5 gm/kg body weight/day). The moderately high-protein diet was associated with a significant increase in renal plasma flow (12%) and glomerular filtration rate (13%) compared with values obtained while the patients followed the low-protein diet. Plasma glucagon levels increased markedly during the intravenous administration of amino acid and the intake of the moderately high-protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Furosemide dynamics in conscious rabbits: Modulation by angiotensin II

Summary The aim of this study was to investigate the effects of an infusion of angiotensin II (50 ng/kg/min) on furosemide pharmacodynamics and kinetics in the conscious rabbit. The protocol included a 90-minute phase to estimate the glomerular filtration rate and the renal plasma flow, followed by a 60-minute phase where 5 mg/kg (n=12) or 10 mg/kg (n=9) of furosemide were administered. During the pre-furosemide phase, compared to control rabbits, angiotensin II increased natriuresis and diuresis. In the presence of angiotensin II, the furosemide-induced natriuresis decreased, that is, it was 174±14 versus 95±25 µmol/min (p<0.05) and 187±17 versus 89±21 µmol/min (p<0.05) for the 5 and the 10 mg/kg doses, respectively. The infusion of angiotensin II decreased renal plasma flow without modifying the glomerular filtration rate, thus the filtration fraction was increased. Angiotensin II increased the area under the furosemide plasma concentrations as a function of time since it decreased its systemic clearance. However, furosemide urinary excretion rate was not altered and its renal clearance decreased slightly without reaching statistical significance. It is concluded that angiotensin II decreases the response to furosemide and the mechanism underlying this effect is related to the pharmacodynamics rather than the kinetics of the diuretic.     

Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: comparison with furosemide

Muzolimine is a loop diuretic with both the dose-dependent increasing effectiveness of loop diuretics and the long-lasting effect of thiazides. This is a potential advantage in the treatment of ascites in advanced cirrhosis since these patients have a low tolerance to sudden reductions of blood volume. Equivalent single, oral doses of furosemide (40 mg) and muzolimine (30 mg) were given to 10 cirrhotic patients with ascites and reduced renal perfusion (glomerular filtration rate = 30 to 75 ml per min). The study was preceded by 4 days of equilibration (dietary sodium 40 mmoles per day), and the drugs were alternated via a single-blind, cross-over protocol after a wash-out period of 3 days. Renal function was monitored under basal conditions and after diuretic administration through 4-hr clearance periods for 24 hr. The renin-aldosterone axis was evaluated before diuretic administration and after 8 and 24 hr. Muzolimine led to a 12-hr cumulative diuresis [AUC0-12 = 2.52 +/- 0.42 (S.E.) ml per min] and natriuresis (5.14 +/- 1.05 mmoles per hr), which were comparable to those of furosemide (2.85 +/- 0.29 ml per min and 6.75 +/- 1.63 mmoles per hr). Its effect, however, was distributed over a longer period (8 hr) than furosemide (4 hr). Muzolimine activity mainly differed from furosemide because of: significantly lower 12-hr potassium excretion (AUC0-12 = 0.28 +/- 0.82 vs. 2.69 +/- 0.46 mmoles per hr; p less than 0.005); greater sodium/chloride excretion ratio (0.45 +/- 0.08 vs. 0.26 +/- 0.06; p less than 0.025), and absence of rebound phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renoprotective effect of small volumes of hypertonic saline solution in chronic heart failure patients with marked fluid retention: results of a case-control study

During intensive therapy of chronic heart failure (CHF) patients with marked fluid retention using high doses of i.v. furosemide the additional effect of agents which might exert osmotic attraction of interstitial fluids has been proposed. They are thought to impede the impairment of renal blood supply and glomerular filtration rate, which may be caused by a combined action of cardiac preload acute reduction, hypotension and neurohormonal activation.We therefore assessed in CHF patients with NYHA class III and BNP values from 900 to 1500 pg/ml, who were treated with i.v. furosemide, the predictors of iatrogenic short term creatinine impairment by means of a case-control observational study from two centers. Patients with CHF had been treated for 6-8 days with intravenous loop diuretics alone or with an additional i.v. administration of other agents (plasma expanders, albumin, mannitol, inotropic support etc.). A rise in serum creatinine ≥ 25% of the basal value was considered as renal impairment.A total of 15 cases and 38 controls were enrolled. At univariate analysis, serum creatinine basal value ≥ 2.2 mg/dl, absence of hypertonic saline solution (HSS) in the therapeutic protocol, hyposodic diet and refractory oligoanuria were associated with an increased risk of worsening renal function precipitated by i.v. diuretic therapy. At multivariate analysis as a predictor of loop diuretic-related renal function impairment, we found a serum creatinine ≥ 2.2 mg/dl at baseline (OR: 63.33, 95% CI: 3.68-1088.73, p=0.0043) and the absence of HSS in the therapeutic regimen (OR: 25.0461, 95% CI: 2.07-302.53, p=0.0113). Moreover, in multivariate analysis ascites had some predictive value of renal deterioration (OR: 13.28, 95% CI: 1.0055-175.41, p=0,0495).     

Glucose-induced changes in renal haemodynamics in proteinuric Type 1 (insulin-dependent) diabetic patients: inhibition by acetylsalicilic acid infusion

Summary The effect of hyperglycaemia on renal function in diabetic nephropathy remains poorly understood. We investigated the renal haemodynamic response to an acute plasma glucose rise from sustained euglycaemia to sustained hyperglycaemia in eight persistently proteinuric Type 1 (insulin-dependent) diabetic patients. Studies were performed in a double-blind cross-over manner after i.v. injection of 450 mg lysine acetylsalicilate (equivalent to 250 mg acetylsalicilic acid) or equal volume of 0.9% NaCl (isotonic saline). In the isotonic saline experiments hyperglycaemia produced a significant rise, by approximately 35%, in glomerular filtration rate in all patients from 41.5±5.2 to 55±6 ml·min^–1·1.73 m^–2 (p<0.005) and an increase in sodium paraminohippurate clearance from 178±22.7 to 220±20.0 ml·min^–1·1.73 m^–2 (p<0.05). These changes took place within the first 30 min of glucose infusion and were maintained for a 90 min hyperglycaemic period. Filtration fraction did not change significantly. Infusion of lysine acetylsalicilate lowered baseline glomerular filtration rate (isotonic saline vs lysine acetylsalicilate 41.5±5.2 vs 30.0±5.7 ml·min^–1·1.73 m^–2; p<0.05) and significantly blunted the rise in glomerular filtration rate during hyperglycaemia (glomerular filtration rate increment: saline vs lysine acetylsalicilate: 13.6±2.8 vs 5.3±1.8 ml·min^–1 ·1.73 m^–2; p<0.005). The effects on renal plasma flow were similarly blunted. In five additional patients, time- and volume-controlled isotonic saline experiments during sustained euglycaemia showed no significant changes in glomerular filtration rate and sodium paraminohippurate clearance. In Type 1 diabetic patients with advanced renal failure, acute hyperglycaemia induces a significant elevation in glomerular filtration rate and renal plasma flow which is likely to be mediated by renal prostaglandin production.     

Effects of cardiac failure on the pharmacokinetics of the diuretic tizolemide

Tizolemide, an alkaline sulphonamide diuretic, was given i.v.in one dose and orally during one week to eight patients withcompensated cardiac failure. They had essentially normal glomerularfiltration rate but reduced renal plasma flow. Tizolemide was almost completely absorbed from the gastrointestinaltract. The drug was mainly eliminated via tubular secretion.Renal clearance of the drug was much lower than in healthy subjectsbecause of low renal plasma flow. As a consequence plasma half–lifewas prolonged considerably in some patients. It was concluded that drugs with mainly tubular renal eliminationmay have a reduced elimination rate in patients with cardiacdiseases despite normal glomerular filtration rate.     

Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites

Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 +/- 27 to 84 +/- 22 mL/min), renal plasma flow (592 +/- 158 to 429 +/- 106 mL/min) and urinary prostaglandin E(2) excretion (3430 +/- 430 to 2068 +/- 549 pg/min) and suppression of the diuretic (urine volume: 561 +/- 128 to 414 +/- 107 mL/h) and natriuretic (urine sodium: 53 +/- 13 to 34 +/- 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% +/- 8% to 47% +/- 8%, P < .05) and thromboxane B(2) production (41 +/- 12 to 14 +/- 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis.     

Diuretic potency of combined hydrochlorothiazide and furosemide therapy in patients with azotemia

The effect of combined hydrochlorothiazide and furosemide therapy was studied in eight hypertensive patients with renal insufficiency who had a poor response to either furosemide or hydrochlorothiazide alone. The study was divided into two parts. In part A, five patients who had an inadequate response to furosemide in doses of 160 to 240 mg/day followed a strict protocol in order to compare the effect of increased doses of furosemide with combined hydrochlorothiazide-furosemide administration. All had azotemia, presumably from nephrosclerosis, and had serum creatinine concentrations ranging from 2.3 to 4.9 mg/dl. Four of the five patients had inadequate arterial pressure control, and the remaining patient had fluid retention from the administration of minoxidil. In all five patients, plasma volume was either increased or normal, despite long-term treatment with furosemide. Increasing the dose of furosemide to between 320 and 480 mg/day had only a modest additional diuretic effect, and plasma volume and arterial pressure were not significantly changed. Adding hydrochlorothiazide, 25 to 50 mg twice a day, produced a marked diuresis, and a significant reduction in weight, plasma volume and mean arterial pressure (p < 0.025 for all three patients). In part B, combined hydrochlorothiazide-furosemide therapy was used to treat three additional patients who had an inadequate response to either diuretic alone. The results indicate that combined hydrochlorothiazide-furosemide is a potent diuretic regimen and is effective in many patients with chronic renal failure who have a poor response to furosemide alone.     

Effects of BG9719 (CVT-124), an A1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure

OBJECTIVES: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF). BACKGROUND: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial. METHODS: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration. RESULTS: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration. CONCLUSIONS: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.     

Effects of somatostatin on renal function in cirrhosis.

To investigate the renal effects of somatostatin in cirrhosis, renal function and plasma and urinary levels of endogenous neurohumoral vasoactive substances were measured in conditions of intravenous water overload (20 mL/kg body wt with 5% glucose) before and during the intravenous infusion of somatostatin (250-500 micrograms/h) in 6 cirrhotic patients without ascites and 17 nonazotemic cirrhotic patients with ascites. Somatostatin induced a significant reduction of renal plasma flow, glomerular filtration rate, and free water clearance in both groups of patients. In patients with ascites, somatostatin also reduced urinary sodium excretion. Changes in renal function were significantly more marked in patients with ascites than in those without ascites and occurred in the absence of changes in mean arterial pressure and plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide. Somatostatin induced a significant reduction in the plasma concentration of glucagon and urinary excretion of prostaglandin E2 that was not related to changes in renal function. These findings indicate that somatostatin administration induces renal vasoconstriction and impairs glomerular filtration rate, free water clearance, and sodium excretion in cirrhosis by a mechanism unrelated to systemic hemodynamics and endogenous neurohumoral vasoactive systems.     

Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function has not been evaluated in patients with congestive heart failure. Therefore, the renal effects of indomethacin were examined in patients with chronic heart failure, and the relation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration was assessed. Twenty-five patients with congestive heart failure and an ejection fraction less than 40% were evaluated. At baseline, renal plasma flow and glomerular filtration rate were measured, using disappearance from the serum of intravenously injected 131I-orthodihippurate and urinary accumulation of intravenously injected technetium-99m diethylenetriamine pentaacetic acid, respectively. After 3 days, 75 mg of sustained release indomethacin were administered, and repeat renal function tests were performed. Mean glomerular filtration rate decreased from 40 +/- 21 to 32 +/- 16 ml/min/1.73 m2 (p less than 0.05), and mean renal plasma flow decreased from 242 +/- 122 to 222 +/- 110 ml/min/1.73 m2 (p less than 0.05). There was no correlation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration. It is concluded that 1 dose of an NSAID may cause marked and clinically important alterations in renal function in patients with heart failure. However, the decrease in glomerular filtration rate does not merely reflect a decrease in renal plasma flow, but probably the effects of NSAIDs on the intraglomerular actions of prostaglandins.     

Renal failure associated with demeclocycline in cirrhosis.

Three patients with cirrhosis, ascites, and dilutional hyponatremia were treated with demeclocycline in an attempt to correct the abnormal water retention. Demeclocycline administration (600 to 900 mg/day for 8 to 9 days) resulted in [a] increased blood urea nitrogen and plasma creatinine concentrations; [b] reduction of the inulin clearance by between 63% to 78% and of paraaminophippurate clearance by 36% to 77%; and [c] an impairment of the renal concentrating ability. Urine osmolality decreased to hypotonic levels, but polyuria did not appear, probably because it was prevented by the reduction of the glomerular filtration rate. Renal failure was reversible on withdrawal of demeclocycline. No other causes than demeclocycline administration could be found to explain the reduction of the glomerular filtration rate and the estimated renal plasma flow.     

Renal failure in minimal change nephrotic syndrome

Renal insufficiency, with serum creatinines ranging from 2.3 to 13.4 mg/dl, was observed in 15 patients with the minimal change nephrotic syndrome. Recovery of renal function occurred in association with diuretic therapy in 13, eight of whom subsequently underwent steroid-induced remission of the nephrotic syndrome. Two patients failed to undergo diuresis or to have a remission of the nephrotic syndrome and died with persistent renal failure.Glomerular filtration rate (C_inulin) was reduced out of proportion to renal plasma flow (C_PAH) as evidenced by remarkably low filtration fractions ranging from 0.03 to 0.095.The invariable association between diuresis and recovery of renal function, the recurrence of renal failure when fluid reaccumulated and the finding of markedly depressed filtration fractions lead us to postulate that renal failure in minimal change nephrotic syndrome may be due to a reversible alteration in glomerular hemodynamics which is related to fluid retention and associated intrarenal edema.     

Effects of single dose of 50mg captopril in patients with liver cirrhosis and ascites

BACKGROUND/AIMS: In patients with liver cirrhosis and ascites, the renin angiotensin system is usually activated. Such a correlation supports the hypothesis that activation of the renin-angiotensin system plays an influential role in the pathogenesis of ascites in liver cirrhosis. METHODOLOGY: In this study, 25 patients with liver cirrhosis and ascites (10 females, 15 males; age: 45-67 years) were enrolled. We evaluated the acute effects of converting enzyme inhibitor (a single dose of 50 mg captopril taken orally) on glomerular filtration rate, effective renal plasma flow, filtration fraction, plasma renin activity, and plasma aldosterone. RESULTS: Oral intake of a single 50 mg dose of captopril significantly decreased glomerular filtration rate (65 +/- 6 mL/min/1.73 m2 vs. 53 +/- 9 mL/min/1.73 m2), filtration fraction (21.2 +/- 2.7% vs. 15.5 +/- 4.1%), and plasma aldosterone (340 +/- 80 pg/mL vs. 247 +/- 42 pg/mL), but increased plasma renin activity (2.65 +/- 2.19 ng/mL/hr vs. 11.58 +/- 2.70 ng/mL/hr) and effective renal plasma flow (312 +/- 41 mL/min/1.73 vs. 356 +/- 60 mL/min/1.73 m2). CONCLUSIONS: We suggest that oral intake of a single dose of 50 mg captopril can block the renin-angiotension system, and result in changes in renal hemodynamics and function in cirrhotic patients with ascites.     

Altered furosemide pharmacokinetics in chronic alcoholic liver disease with ascites contributes to diuretic resistance

Some patients with chronic alcoholic liver disease and ascites have an impaired natriuretic response to furosemide. To elucidate the mechanism of this diuretic resistance, we measured para-aminohippurate and inulin clearances and urinary excretion of electrolytes, prostaglandin E2, and furosemide after intravenous administration of 80 mg of furosemide in 26 patients. The natriuretic response was variable (3.3-172 mEq/h) and was unrelated to basal sodium excretion, renal clearances, or urinary prostaglandin E2. Natriuresis correlated negatively with plasma aldosterone (r = -0.54, p less than 0.01), and strongly with urinary furosemide (range 5.5-76 mg/h, r = 0.71, p less than 0.001). As urinary furosemide excretion reflects the amount of furosemide reaching the active site on the luminal side of the tubule, the data demonstrate markedly reduced amounts of furosemide at its primary site of action in patients with diuretic resistance. Plasma furosemide was higher in patients with reduced furosemide excretion and impaired natriuresis, suggesting that the defect was an impairment of furosemide transport into the tubule. Thus, a major factor in diuretic resistance is altered furosemide pharmacokinetics.     

Unpredictability of clinical evaluation of renal function in cirrhosis: Prospective study

The natural course of renal function in patients with cirrhosis and ascites but without azotemia is unclear. Therefore, a prospective evaluation of 23 non-azotemic cirrhotic patients with ascites was carried out over a three-year interval. Assessment included evaluation of serum electrolyte values, liver function tests, plasma renin levels, and parathyroid hormone levels. Renal function was determined by measurement of clearances of water and solute excretion, and simultaneous clearances of para-amino hippurate, inulin, and creatinine. The initial mean glomerular filtration rate was 66 mi/minute, serum creatinine level was 1.1 mg/dl, and blood urea nitrogen value was 13 mg/dl. The glomerular filtration rate showed marked variability among patients. On the basis of initial glomerular filtration rate, the patients were divided into three groups. Group I consisted of patients with supranormal filtration rates (mean 183 ml/minute), Group II constituted patients with normal filtration rates (mean 92 ml/minute), and Group III comprised patients with severely impaired filtration rates (mean 32 mi/minute). The serum creatinine level was below 1.5 mg/dl in all three groups. Serial measurement of renal function was performed in 18 patients over a mean of 310 days (range four to 1,176 days). Eighty-six percent of patients studied from Groups I and II maintained a normal or supranormal glomerular filtration rate over one year. However, most patients in Group III showed a progressive decline in filtration rate, despite no change in serum creatinine value. Sixty-seven percent of Group III patients died over a mean of one year. The mean 24-hour solute excretion among Group III patients was only 263 mOsm per day, significantly less than the control value of 874 mOsm per day in other hospitalized non-cirrhotic patients. The serum creatinine level frequently failed to rise above normal even when the glomerular filtration rate was very low (less than 25 ml/minute), and creatinine clearance overestimated inulin clearance by a factor of two in Group III patients. However, the creatinine index was an aid in determining true glomerular filtration rate and may be a useful clinical test in the evaluation of renal insufficiency in cirrhotic patients with normal serum creatinine values. Many patients with cirrhosis and ascites will have a glomerular filtration rate of less than 60 ml/minute but a normal serum creatinine level. These patients may constitute a previously unrecognized large group.     

Factors influencing vascular and natriuretic responses to ANP

To explore factors that modulate the magnitude of vasorelaxation and natriuretic/diuretic responses to exogenous ANP, clearance studies were performed in unilateral hydronephrotic rats with renal vasoconstriction complications. An increase in renal plasma flow associated with a decrease in calculated renal vascular resistance in response to ANP (2 micrograms.min-1.kg-1, i.v.) was obtained only in the hydronephrotic kidney. In contrast, the control kidney of the unilateral hydronephrotic rat had a decrease in glomerular filtration rate and an abolished natriuretic response following ANP administration. A prior renal denervation in the control kidney restored the natriuretic effect of ANP and abolished the lowering of glomerular filtration rate. These data suggest that the vasodilatory effect of ANP may depend on the vascular tone itself, and that renal responses to ANP are significantly modified by renal nerve activity.     

Hypertension and stenosis of the graft artery: effects of conversion enzyme inhibition

The use of angiotensin converting enzyme inhibitors may lead to reversible renal insufficiency in transplant patients with transplant renal artery stenosis (TRAS). We assessed acute effects of captopril (50 mg, p. os) in 7 cadaver kidney recipients (mean age: 35.6 +/- 4 yrs) with TRAS, 9 to 46 mo after transplantation. All patients were treated by prednisolone and azathioprine. After captopril administration, mean arterial pressure decreased from 127 +/- 6 to 119 +/- 7 mmHg, effective renal plasma flow from 152 +/- 19 to 118 +/- 19 ml/min/1.73 m2, glomerular filtration rate from 59 +/- 8 to 39 +/- 10 ml/min/1.73 m2 and filtration fraction from 0.39 +/- 0.02 to 0.32 +/- 0.07. Among the 7 patients, 2 developed immediate and transient anuria; 4 presented a net decrease of GFR, only one had stable GFR. This patient was chronically treated by captopril; as BP was not controlled, furosemide (40 mg p. os) was added. Serum creatinine increased from 180 to 250 mumol/l. Percutaneous angioplasty was done without decrease in BP; however, treatment by captopril and furosemide could be reinstitued without deterioration in renal function. We conclude that: acute renal failure in kidney graft recipients with TRAS is frequent, but not mandatory; sodium depletion induced by diuretics enhances the fall in GFR; acute effect of captopril must be assessed in patients with TRAS before the use of this product as long term antihypertensive treatment.     

Effects of converting enzyme inhibition on split renal function in renovascular hypertension

The effects of captopril on effective renal plasma flow and glomerular filtration rate were studied using a noninvasive radioisotopic method on individual kidneys in eight patients with renovascular hypertension and 12 patients with essential hypertension with various renin levels. Four patients with renovascular hypertension had unilateral while three had bilateral renal artery stenosis. The effective renal plasma flow and glomerular filtration rate were determined by using 131I-iodohippurate sodium and 99mTc-diethylenetriamine pentaacetic acid, respectively. Glomerular filtration rate and effective renal plasma flow were significantly reduced in the stenotic kidneys of patients with renovascular hypertension compared with values in nonstenotic kidneys (p less than 0.01). Treatment with captopril, 37.5 to 75 mg/day for 1 to 48 weeks, further reduced the glomerular filtration rate only in stenotic kidneys, and effective renal plasma flow increased in both kidney types. In two of the three renal hypertensive patients with bilateral renal artery stenosis, captopril produced a reversible azotemia that was unrelated to the fall in blood pressure, as evidenced by the lack of azotemia seen after a moderate blood pressure reduction induced by other antihypertensive medications. These results indicate that endogenous angiotensin II is essential in maintaining the glomerular filtration rate in stenotic kidneys and suggest that a reduction in glomerular filtration rate during captopril administration could indicate the presence of renal artery stenosis.     

Attenuated renal excretory response to atrial natriuretic peptide in congestive heart failure in man.

The renal and hormonal effects of atrial natriuretic peptide given as a bolus injection (2.0 micrograms/kg) were studied in 12 patients with congestive heart failure before and after treatment with captopril for 4 weeks and in 13 healthy control subjects. Atrial natriuretic peptide caused a rise in urinary excretion of sodium and urinary flow in the controls, whereas no increases were observed in the patients. Both proximal and distal fractional reabsorption of sodium, as evaluated by the lithium clearance technique, decreased less in the patients than in the controls. Basal plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP), and the basal urinary excretion of cGMP, were elevated in the patients. The increases in both plasma and urinary cGMP after administration of atrial natriuretic peptide were blunted in heart failure. Basal glomerular filtration rate and renal plasma flow were reduced, and filtration fraction increased, in the patients. A positive correlation (r = 0.958, P less than 0.01) was found between renal plasma flow and the relative increase in urinary excretion of sodium in the patients with heart failure. Treatment with captopril did not improve the natriuretic and diuretic effect of exogenous atrial natriuretic peptide, but resulted in an increase in filtration fraction after administration of atrial natriuretic peptide not present before captopril.(ABSTRACT TRUNCATED AT 250 WORDS)