Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155/101 (20.6/13.5) +/- 11/4 (1.5/0.5) to 139/88 (18.5/11.7) +/- 16/9 (2.1/1.2) mmHg (kPa) (means +/- SD; P less than 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates were also unchanged, as were potassium clearance, urine flow and body weight. 3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment caused a redistribution of tubular sodium reabsorption without a change in overall sodium excretion or body fluid compartments.     

Hypertension and renal dysfunction in primary hyperparathyroidism: effect of parathyroidectomy

1. Twenty-four patients with primary hyperparathyroidism were studied before and 18 restudied 6.5 months (mean) after parathyroidectomy, to investigate the pathogenesis of the hypertension which may accompany this condition. Comparison was made with age-matched patients with essential hypertension and with normotensive control subjects. 2. There was a significant inverse relationship between mean arterial pressure and 51Cr-labelled ethylene-diaminetetra-acetate (51Cr-EDTA) clearance in patients with hyperparathyroidism both before and after parathyroidectomy, but not in patients with essential hypertension. 3. Creatinine clearance appeared to overestimate glomerular filtration rate in some patients with hyperparathyroidism, falling significantly after surgery while 51Cr-EDTA clearance was unchanged. This observation may explain the failure of some previous studies to relate hypertension to impairment of renal function. 4. Plasma renin activity, plasma aldosterone and whole-body exchangeable sodium did not differ between normotensive and hypertensive patients with primary hyperparathyroidism and were unchanged after surgery. 5. Parathyroidectomy did not result in any change in blood pressure or in glomerular filtration rate measured by 51Cr-EDTA clearance.     

阻塞性睡眠呼吸暂停综合征与高血压的相关性

目的 探讨阻塞性睡眠呼吸暂停综合征(OSAS)与高血压的相关性.方法 按照睡眠资料和24 h血压资料,分为单纯高血压组与合并OSAS高血压组,口服药物治疗4周,比较治疗前后血压变化,OSAS组降压效果差的患者同时接受持续气道正压(CPAP)治疗,观察血压控制情况.结果 30例单纯高血压患者,常规药物降压治疗4周后,血压较治疗前明显下降(P<0.05);OSAS组药物治疗前后无明显变化,再同时用CPAP治疗4周后晨起血压明显下降.结论 合并有OSAS的高血压患者多为难治性,单纯降压药物治疗效果欠佳,需要同时应用CPAP治疗.     

Effects of packed cell volume reduction on renal haemodynamics and the renin-angiotensin-aldosterone system in patients with secondary polycythaemia and hypoxic cor pulmonale

Polycythaemia was corrected by erythrapheresis in ten patients with hypoxic cor pulmonale who were stable on regular diuretic therapy. Renal haemodynamics, renal function and the renin-angiotensin-aldosterone system were assessed before and afterwards. Before erythrapheresis effective renal plasma flow (ERPF) was reduced (63% predicted) but glomerular filtration rate (GFR) was preserved (88% predicted) by a rise in filtration fraction (FF) (138% predicted). A negative correlation existed between ERPF and packed cell volume (r = -0.723; P less than 0.02) and also between ERPF and PaCO2 (r = -0.710; P less than 0.05). Polycythaemia was sufficient to maintain renal oxygen delivery (97% predicted). After erythrapheresis systemic blood pressure, blood volume and blood viscosity all decreased. ERPF increased by 18% (P less than 0.02). FF fell by 11% (P less than 0.05) and GFR was unchanged. Renal oxygen delivery diminished by 25% (P less than 0.001). Plasma renin activity was increased in five patients and plasma aldosterone increased in two patients before erythrapheresis. No sustained fall occurred in plasma renin activity or plasma aldosterone, possibly because the haemodynamic consequences of the procedure had opposing actions on renin secretion. Although the reduction in FF would per se tend to enhance renal sodium and water excretion, a diuresis or natriuresis did not occur consistently.     

Feedback-mediated reduction in glomerular filtration during acetazolamide infusion in insulin-dependent diabetic patients.

1. A sustained high glomerular filtration rate in diabetes mellitus is associated with increased proximal reabsorption, suggesting alterations in the tubuloglomerular feedback system. To test this hypothesis, renal function was studied in eight control subjects and 14 recent-onset euglycaemic insulin-dependent diabetic patients before and after infusion of the carbonic anhydrase inhibitor, acetazolamide (5 mg/kg body weight). 2. Acetazolamide induced a dramatic fall in glomerular filtration rate in both diabetic patients and control subjects (from 138 +/- 5 to 114 +/- 4 and from 127 +/- 3 to 113 +/- 2 ml min-1 1.73 m-2, respectively, P less than 0.0001). This fall in glomerular filtration rate was strongly correlated with the acetazolamide-induced decrease in absolute proximal reabsorption calculated by using lithium clearance. 3. To further assess the potential role of angiotensin II in the acetazolamide-induced tubulo-glomerular feedback response, 11 additional diabetic patients were investigated before and after the administration of acetazolamide plus the angiotensin-converting enzyme inhibitor, enalaprilat (1.25 mg intravenously). Despite the effective blockade of angiotensin II formation and a slight decrease in renal vascular resistance, the glomerular filtration rate fell significantly and by a similar magnitude as seen with acetazolamide alone. 4. These results indirectly suggest that there is an altered basal tubulo-glomerular feedback system in diabetic patients but a normal response to the increase in distal delivery. No convincing role for an angiotensin II-mediated effect on the afferent limb of the tubuloglomerular feedback response could be demonstrated.     

The acute effect of acetazolamide on glomerular filtration rate and proximal tubular reabsorption of sodium and water in normal man

The acute effects on kidney function of acetazolamide (250 mg) given intravenously were evaluated in seven healthy subjects. Glomerular filtration rate was measured as the renal clearance of 51Cr-EDTA, and fluid flow rate out of the proximal tubules was assessed by measurement of the renal lithium clearance. An 18% decline in glomerular filtration rate (ml/min) was observed after acetazolamide administration (109 +/- 16 vs 89 +/- 14, p less than 0.02), while lithium clearance (ml/min) increased by 35% (30 +/- 5 vs 38 +/- 8, p less than 0.02). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one third (79 +/- 12 vs 51 +/- 9, p less than 0.02), and fractional proximal reabsorption of water and sodium (%) declined (73 +/- 2 vs 58 +/- 6, p less than 0.02). Renal sodium clearance and absolute distal reabsorption of sodium increased, while fractional distal reabsorption of sodium declined. Acetazolamide reduces absolute and fractional proximal tubular reabsorption of sodium and water, and glomerular filtration rate. Primarily, this induces an increase in the output of fluid from the proximal tubules accounting for the diuretic effect of the drug. The acute fall in glomerular filtration rate is probably mediated by a temporary increase in proximal intratubular pressure and activation of the tubuloglomerular feedback mechanism.     

Renal tubular site of action of felodipine

The renal tubular site of action of felodipine was localized using renal clearance and recollection micropuncture techniques in the anesthetized rat. In initial renal clearance experiments, felodipine (2.75 nM/kg/min i.v. X 60 min) had no effect on mean arterial pressure or glomerular filtration but significantly increased urinary flow rate, sodium and potassium excretion. In subsequent recollection micropuncture experiments, felodipine decreased mean arterial pressure but did not affect renal blood flow or renal vascular resistance or glomerular filtration rate; absolute and fractional urinary excretion of sodium and water, but not potassium, were increased. Proximal tubular and loop of Henle sodium, potassium and water reabsorption were not affected but distal tubular and collecting duct sodium and water (not potassium) reabsorption were decreased by felodipine. Felodipine is a vasodilator antihypertensive agent which, in doses which decrease mean arterial pressure in normotensive rats, increases urinary flow rate and sodium excretion by inhibiting distal tubular and collecting duct sodium and water reabsorption; potassium reabsorption or excretion is not affected. As a vasodilator antihypertensive agent, felodipine possesses beneficial natriuretic rather than detrimental sodium retaining properties.     

Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs

OBJECTIVE: It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. DESIGN: Prospective, randomized, controlled experiment. SETTING: University-based animal laboratory and research unit. SUBJECTS: Eight female beagle dogs. INTERVENTIONS: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. MEASUREMENTS AND MAIN RESULTS: Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). CONCLUSIONS: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.     

The Renal Handling of Insulin

The renal handling of insulin was studied by insulin immunoassay in arterial blood, renal venous blood, and urine of fasting patients with normal renal function and in peripheral venous blood and urine of normal subjects and patients with renal disease before and after an oral glucose load. A renal arteriovenous insulin concentration difference of approximately 29% was found and suggests that in normal subjects renal insulin clearance is significantly in excess of glomerular filtration rate. The insulin excreted in the urine of normal individuals at no time exceeded 1.5% of the load filtered at the glomerulus. This contrasts with the finding of a urinary insulin clearance approaching glomerular filtration rate in patients with severely impaired renal tubular function.It is suggested that insulin is normally filtered at the glomerulus and then almost completely reabsorbed or destroyed in the proximal tubule. If reabsorption occurs, as seems more likely, reabsorbed insulin does not return to the renal vein and is presumably utilized in renal metabolism together with insulin taken up directly from the blood.Caution is advised in the use of urinary insulin concentration or excretion as an index of serum insulin level or insulin secretion because a very small and variable proportion of filtered insulin appears in the urine in normal subjects, and major changes in urinary insulin excretion may arise as a result of minor tubular defects.     

Acute effects of captopril and ibuprofen on proteinuria in patients with nephrosis

Captopril decreases protein excretion in patients with nephrosis. To evaluate whether captopril has an acute antiproteinuric effect and to evaluate the role of changes in renal hemodynamics or glomerular permselectivity on this effect, renal clearance studies were performed in patients without diabetes but with nephrosis. Protein excretion and renal hemodynamics were measured at baseline and after the administration of captopril. To measure the contribution of renal prostaglandins, patients were restudied on a separate day, after the combined administration of captopril and the prostaglandin synthetase inhibitor ibuprofen. Both treatments significantly reduced mean protein excretion, but the change was greater with combined therapy than with captopril alone (40.6% vs 20.0%). Mean glomerular filtration rate (GFR) decreased by 4.8% (not significant) and 16.5% (p less than 0.001), and filtration fraction (FF) decreased by 13.6% (p less than 0.001) and 14.9% (p less than 0.001) after captopril alone and combined therapy, respectively. No significant correlation was found between changes in proteinuria and changes in GFR or FF after treatment with captopril alone. In contrast, the decrease in proteinuria correlated with the change in GFR after combined drug administration (r = 0.68, p = 0.06). The ratio of immunoglobulin G to albumin clearance, an index of glomerular permselectivity, was unaffected by captopril but decreased significantly (by 43%) after combined drug administration. The results suggest that the acute antiproteinuric effect of captopril is not due to changes in FF, GFR, or glomerular perselectivity. The addition of ibuprofen enhances the antiproteinuric effect of captopril by decreasing the GFR as well as by enhancing the permselectivity of the glomerular capillary membrane.     

Effect of sympathetic blocking agents on the antinatriuresis of reflex renal nerve stimulation.

To evaluate the effects of reflex renal sympathetic nerve stimulation on renal tubular sodium handling, clearance studies were performed in anesthetized dogs. With renal perfusion pressure held constant, baroreceptor reflex renal sympathetic nerve stimulation was produced by controlled arterial hemorrhage or carotid sinus perfusion. Significant decreases in urinary sodium excretion occurred in the presence of minor insignificant alterations in renal blood flow and no changes in glomerular filtration rate. Renal alpha adrenergic receptor blockade (phenoxybenzamine) or adrenergic blockade (guanethidine) completely reversed the fall in urinary sodium excretion; this could not be attributed to alterations in glomerular filtration rate or renal blood flow. These studies support the interpretation that adrenergic innervation of the renal tubules is involved in the regulation of renal tubular sodium reabsorption.     

Effects of Felodipine on the dog kidney: a lithium clearance study.

This study was performed in order to investigate the possible influence of sympathetic nerve activity on the effects of the dihydropyridine calcium antagonist felodipine on absolute and fractional reabsorption rates of sodium and water in proximal and distal tubular segments in the dog kidney. Clearance of 51Cr-EDTA was used as a measure of glomerular filtration rate (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance (C-Li) were used for assessing the absolute and fractional tubular reabsorption rates. Felodipine infusion into the right renal artery increased renal vascular conductance (renal blood flow divided by renal arteriovenous pressure gradient) significantly (by 9%) while GFR remained unchanged. Calculated absolute proximal reabsorption rates remained unchanged while distal sodium reabsorption rate increased significantly from 2.1 +/- 0.3 to 2.7 +/- 0.4 mmol min-1. Sodium clearance (C-Na) increased from 0.22 +/- 0.08 to 0.40 +/- 0.07 ml min-1. The alpha-adrenergic blockade with phentolamine did not affect renal haemodynamic or excretory variables, nor did it influence the haemodynamic response to felodipine. After alpha-adrenergic blockade felodipine caused an increase in C-Na from 0.28 +/- 0.06 ml min-1 to 0.63 +/- 0.04 ml min-1, which was significantly greater than that measured after felodipine alone. The distal load (C-Li) was not significantly different from that obtained after felodipine alone, but distal sodium reabsorption rate increased less significantly after alpha-adrenergic blockade. The results suggest that felodipine, by its effect on tubular flow and/or composition, activates local alpha-adrenergic reflex mechanism(s), which stimulates distal sodium reabsorption, thereby attenuating the natriuretic effect.     

Systemic and Renal Haemodynamics, Body Fluids and Renin in Benign Essential Hypertension with Special Reference to Natural History

Abstract. Forty patients with uncomplicated essential hypertension were investigated with respect to diurnal variability of arterial pressure (indirect recordings), intra-arterial pressure, cardiac output, plasma volume, renal plasma flow and glomerular filtration rate. Extracellular volume was estimated in 17, plasma renin concentration in 33 and vector-cardiograms were recorded in 27 patients. Treatment was discontinued at least a fortnight before and sodium intake was standardized.—Blood pressure varied across a wide range. Variability (lability) of blood pressure was quantified by expressing the difference between highest and lowest automatic blood pressure readings as a percentage of the highest reading. Cardiac output correlated with variability of blood pressure, blood volume and renal blood flow.—Plasma renin concentration was correlated with renal vascular resistance and filtration fraction.— QRS magnitude appeared to be related with the level of arterial pressure.—Haemodynamic variables exhibited a definite relationship with age, deviating in part from distribution according to age in normal populations.     

High-dose amino acid infusion preserves diuresis and improves nitrogen balance in non-oliguric acute renal failure

INTRODUCTION: The effects of protein-enriched diets on glomerular filtration have been described in normal subjects and in patients with chronic renal failure. In acute renal failure, the effects of administration of high rates of protein on renal function and nitrogen balance have not been studied in critically ill patients. The present study examines the effects of large doses of amino acids on the glomerular filtration rate and nitrogen balance in critically ill patients with acute renal failure. METHODS: Fourteen critically ill patients with a creatinine clearance below 50 ml/min and conserved diuresis above 2,000 ml/day received 2000 non-protein kcal/day and either 75 g (Group 1) or 150 g (Group 2) of amino acids parenterally. Renal function tests, fluid balance, sodium and nitrogen balances, and furosemide administration were assessed on day 1 (baseline day when dextrose 5% was administered) and days 2, 3 and 4. RESULTS: The two groups were comparable in terms of severity indices, sex and creatinine clearance. Group 2 was significantly older (p < 0.05). Blood urea nitrogen increased significantly in Group 1 but not in Group 2; creatinine clearance remained unchanged in the two groups. Group 2 patients had a significantly more positive cumulative nitrogen balance (-10.5 +/- 17 g/day vs. 9 +/- 8.3 g/day) (p < 0.01), less positive fluid balance (2003 +/- 1336 ml vs. -2407 +/- 1990 ml) and lower furosemide requirement (1003 +/- 288 mg vs. 649 +/- 293 mg) (p < 0.05). CONCLUSION: A high amino acid regimen administered as a part of parenteral nutrition improves nitrogen balance, reduces furosemide requirements and ameliorates water balance in acute renal failure patients with conserved diuresis.     

Role of the renal nerves in modulating renin release during pressure reduction at the feline kidney

Experiments were undertaken in pentobarbitone-anaesthetized cats to determine how reflex activation of the renal nerves altered the responsiveness of the kidney to release renin during reductions in renal perfusion pressure. Reflex activation of the renal nerves was achieved by reducing carotid sinus perfusion pressure by 30 mmHg, which increased systemic blood pressure. During this period renal perfusion pressure was regulated at control levels and neither renal blood flow nor glomerular filtration rate changed, but there was a significant decrease in sodium excretion and increase in renin secretion. Renal denervation abolished both these latter responses. Renal perfusion pressure reduction, by 25-30 mmHg, had no effect on renal blood flow or glomerular filtration rate but significantly decreased sodium excretion and increased renin secretion. Simultaneous reduction of carotid sinus and renal perfusion pressures had no effect on renal blood flow or glomerular filtration rate, decreased sodium excretion, and the magnitude of the increase in renin secretion was significantly greater than that obtained with reduction in renal perfusion pressure alone. Renal denervation abolished the increase in renin secretion during these manoeuvres. During atenolol administration, renal haemodynamics and sodium excretion responses to renal pressure reduction were similar to those obtained in the absence of the drug. Renin secretion was increased, but significantly less than in the absence of atenolol. Simultaneous carotid sinus and renal pressure reductions during atenolol administration had no effect on renal haemodynamics, reduced sodium excretion and increased renin secretion, the magnitude of which was significantly greater than that recorded with only renal pressure reduction in the presence of atenolol. Direct electrical stimulation of the renal nerves, at frequencies which caused a 5-10% reduction in renal blood flow, did not change glomerular filtration rate, decreased sodium excretion by 30% and increased the rate of renin secretion twofold. In the presence of atenolol, such renal nerve stimulation reduced renal blood flow to the same degree, did not change filtration rate, decreased sodium excretion by 37% but did not change renin secretion. These results show that the magnitude of the release of renin in response to renal pressure reduction is dependent on activity within the renal nerves, being blunted after denervation, and enhanced during reflex activation of the renal nerves.     

Effect of a kinin antagonist on renal function and haemodynamics during alterations in sodium balance in conscious normotensive rats

1. To evaluate whether sodium intake can modulate the action of endogenous kinins on renal function and haemodynamics, a receptor antagonist of bradykinin was infused in conscious normotensive rats maintained on either a normal or a low sodium diet. 2. The antagonist inhibited the hypotensive effect of exogenously administered bradykinin. It did not change the vasodepressor effect of acetylcholine, dopamine or prostaglandin E2. 3. The antagonist did not affect mean blood pressure, glomerular filtration rate, renal blood flow or urinary sodium excretion, in rats on sodium restriction. It did not change mean blood pressure, glomerular filtration rate or urinary sodium excretion, but decreased renal blood flow, in rats on a normal sodium intake. 4. The kallikrein-kinin system has a role in the regulation of renal blood flow in rats on a normal sodium diet.     

Intrarenal effects of ecadotril during acute volume expansion in dogs with congestive heart failure

Neutral endopeptidase 24.11 (NEP) inhibitors are known to have vascular, diuretic, and natriuretic effects that may be helpful in the treatment of congestive heart failure (CHF). Most NEP inhibitors may act principally through intrarenal mechanisms, which are not completely understood. The purpose of this study was to determine the principal renal effects of the NEP inhibitor ecadotril in dogs with progressive CHF induced by rapid ventricular pacing. Renal function was measured before, during, and after acute i.v. infusion of normal saline in a total of six dogs during normal cardiac function, early left ventricular dysfunction, and overt CHF. During overt CHF, each dog was treated with either ecadotril or placebo orally for 1 week. Parameters measured included glomerular filtration rate, renal blood flow, urine output, sodium clearance, sodium fractional excretion, and proximal and distal sodium reabsorption. Ecadotril treatment resulted in increased urine output, sodium clearance, and renal sodium excretion relative to placebo-treated controls. The principal intrarenal effect of ecadotril was decreased distal renal tubular sodium reabsorption. Both glomerular filtration rate and renal blood flow declined during overt CHF and were unaffected by ecadotril treatment. The results of this study are consistent with the principal action of ecadotril occurring by way of intrarenal events as opposed to changes in renal hemodynamics. The principal effect of ecadotril on distal tubular sodium reabsorption suggests that inhibition of NEP activity in the proximal renal tubules may allow increased binding of filtered atrial natriuretic peptide to natriuretic peptide receptor sites in the distal renal tubules and collecting ducts.     

Effects of probucol in renal function and structure in rats with subtotal kidney ablation.

Probucol is a bisphenolic compound that lowers serum cholesterol and also has potent antioxidant properties. The present studies examined the effects of probucol administration on renal function and structure in a rat model of subtotal renal ablation. After subtotal nephrectomy, rats were fed an isocaloric rat chow diet containing 22.8% protein with or without the addition of 1% probucol. After 4 weeks, clearance studies were performed for determination of glomerular filtration rate (inulin clearance) and effective renal plasma flow (paraaminohippurate clearance). After completion of clearance studies and measurements of arterial blood pressure, the animals were exsanguinated and renal tissue was obtained for histologic evaluation. There were no differences in body weight, hematocrit, and blood pressure between the two groups of rats 4 weeks after subtotal nephrectomy. Rats with a remnant kidney given probucol had a significantly lower serum cholesterol level (47.4 +/- 5.3 mg/dl vs 87.2 +/- 10.4 mg/dl) and urea nitrogen level (40.7 +/- 3.2 mg/dl vs 63.6 +/- 8.1 mg/dl) than the control group. Rats given probucol also had significantly greater values for inulin clearance and clearance of paraaminohippurate and significantly less proteinuria than control rats. Also, rats with a remnant kidney given probucol had a significantly greater number of normal glomeruli (6.2% +/- 2.1% vs 1.1% +/- 0.9%) and a lesser number of severely affected glomeruli, grades III and IV (26.0% +/- 5.9% vs 50.9% +/- 9.1%) than rats with a remnant kidney not given probucol. Tubulointerstitial changes also were significantly less in rats with a remnant kidney given probucol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lomefloxacin pharmacokinetics in subjects with normal and impaired renal function.

Lomefloxacin pharmacokinetics were investigated in 6 normal subjects and 24 uremic patients after a single oral dose of 400 mg. In subjects with normal renal function, the peak level in plasma averaged 3.5 +/- 0.9 micrograms/ml (mean +/- standard deviation) and was obtained at 1.3 +/- 0.9 h. The absorption rate constant was 3.8 +/- 1.6 h-1. The terminal half-life was 7.77 +/- 0.95 h. The apparent volume of distribution was 2.54 +/- 0.66 liters/kg. Total body and renal clearances were 259 +/- 83 and 200 +/- 55 ml/min per 1.73 m2, respectively. The percentage of the dose recovered unchanged in 48-h urine was 80.6 +/- 2.8. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 38 h in severely uremic patients (glomerular filtration rate, less than 10 ml/min). Renal insufficiency did not significantly modify the peak level in plasma, the time to peak, the apparent volume of distribution, or the nonrenal clearance of lomefloxacin. The dialysis clearance of lomefloxacin was 54 +/- 13 ml/min. Linear relationships were found between lomefloxacin pharmacokinetic parameters and glomerular filtration rate data. Dosage adjustments are necessary in uremic patients.     

Effects of exercise on glomerular passage of macromolecules in patients with diabetic nephropathy and in healthy subjects.

The effects of exercise on glomerular permeability were investigated in 12 proteinuric insulin-dependent diabetic patients and in 12 healthy controls by measuring the fractional protein and dextran clearances at rest and after exercise. Exercise significantly reduced the glomerular filtration rate (GFR) and the renal plasma flow (RPF) and markedly increased the filtration fraction (FF) in both diabetics and controls. The fractional clearances of albumin and IgG increased significantly during exercise in diabetics. Exercise also significantly increased the fractional clearance of albumin in healthy controls. The changes in the fractional protein clearances correlated significantly with the changes in the FF. In diabetics the fractional dextran clearances of molecules with a radius greater than or equal to 4.8 nm were significantly elevated after exercise. This was not found in healthy controls. It is concluded that exercise increases glomerular permeability by influencing the renal haemodynamics. Probably partial depletion of negative charges on the glomerular capillary wall plays a role in exercise-induced proteinuria in both healthy and diabetic subjects. In addition, the altered glomerular permeability during exercise is associated with increased size of the filtering pores in diabetic nephropathy.