Influence of posture on haemodynamics, sodium and hormonal homeostasis in cirrhotic patients with and without ascites

BACKGROUND/AIMS: Previous studies in preascitic cirrhosis demonstrated sodium retention during upright posture and sodium hyperexcretion during bed-rest. In patients with ascites, sodium excretion and creatinine clearance decreased during upright posture. Head-down tilting (HDT) accentuated the natriuretic effect of bed-rest in short term studies. The aim of this study was to evaluate the effects of prolonged change in posture on sodium homeostasis and on haemodynamics in cirrhotic patients. METHODS: Eighteen cirrhotic patients (9 with, 9 without ascites), were studied during 12 h upright, supine and HDT position (-10 degrees). During each position, 12 h urine collections were performed and blood samples were obtained before and after change in position. Non-invasive systemic hemodynamic measurements were performed. RESULTS: There was no significant difference between HDT and supine position in both ascitic and preascitic groups for urinary volume, fractional sodium excretion, creatinine clearance, urinary and plasma hormones and hemodynamics. Urinary volume (in supine and HDT) and fractional sodium excretion (in supine) were significantly higher and urinary noradrenaline and plasma renin (in supine and HDT) significantly lower in the preascitic group compared with the ascitic patients. Cardiac output and heart rate decreased after 12 h supine and HDT, suggesting a deactivation of sympatic nervous system and catecholamines. CONCLUSION: Our results demonstrate that prolonged HDT had no advantage over normal bed-rest in both patient groups. Possibly, a short-term beneficial effect of HDT was lost after several hours.     

The Effects of Chronic Administration of Indomethacin and Misoprostol on Renal Function in Cirrhotic Patients with and without Ascites

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) often cause renal dysfunction in cirrhotic patients with ascites through inhibition of prostaglandin synthesis. However, their renal effects in cirrhotic patients without ascites are controversial. In addition, the role of prostaglandins in cirrhotic patients with ascites and in non-ascitic cirrhotic patients receiving NSAIDs also remains elusive. Thus we evaluated the chronic renal effects of indomethacin and misoprostol in 9 cirrhotic patients with ascites (protocol 1) and 21 cirrhotic patients without ascites (protocol 2).

Methods: The patients of protocol I received 200 μg of misoprostol every 6 h for 7 consecutive days. In protocol 2, 11 patients received 25 mg indomethacin three times a day for 7 consecutive days. The other 10 patients received 25 mg indomethacin three times a day plus 200 μg misoprostol every 6 h for 7 consecutive days. Renal function tests, plasma renin activity, and plasma aldosterone concentration were measured before and after treatment.

Results: In protocol 1, misoprostol tended to reduce the urinary sodium excretion (p = 0.08). In protocol 2, indomethacin alone greatly impaired renal plasma flow (p < 0.05), creatinine clearance (p < 0.05), blood urea nitrogen (p < 0.05), and serum creatinine (p = 0.06) in 11 patients. Similar magnitudes of renal dysfunction were observed in the other 10 patients despite the concomitant misoprostol treatment.

Conclusion: Chronic administration of misoprostol may have caused a negative natriuretic effect in cirrhotic patients with ascites. In cirrhotic patients without ascites chronic administration of indomethacin may induce a renal dysfunction that cannot be reversed by misoprostol.     

Renal prostaglandin E2 and other vasoactive modulators in refractory hepatic ascites: response to peritoneovenous shunting

To assess the role of renal prostaglandin E2 in the pathogenesis of refractory ascites, in relation to renal sodium handling and circulating levels of vasoconstrictive substances, we studied 12 cirrhotic patients with refractory ascites before and after peritoneovenous shunting. Baseline values for urinary prostaglandin E2 excretion, sodium excretion, and creatinine clearance, as well as serum aldosterone, plasma renin activity, and plasma free norepinephrine, were obtained preoperatively with patients on a sodium- and fluid-restricted diet. Diuretics were also withheld. Similar parameters were measured immediately postoperatively during four consecutive 2-h intervals, then again at 2 wk and 3 mo. In patients with refractory ascites, mean baseline urinary prostaglandin E2 excretion was significantly elevated (2.5 +/- 0.8 pmol/min), compared with that in both normal controls and cirrhotics without ascites (1.3 +/- 0.3 pmol/min). A significant natriuresis occurred immediately postoperatively and persisted at 2 wk and 3 mo. Concomitantly, the elevated levels of preoperative vasoconstrictor substances gradually normalized by 2 wk. Urinary prostaglandin E2 excretion, however, rose transiently in the immediate postoperative period and then fell gradually to within the normal range by 3 mo. Enhanced renal prostaglandin E2 synthesis, therefore, does not play a role in the sustained improvement in sodium homeostasis after peritoneovenous shunting in patients with refractory ascites.     

Effects of "body compression" on parameters related to ascites formation: therapeutic trial in cirrhotic patients

Decreased effective circulating blood volume is an important factor in ascites formation in liver cirrhosis. We designed a "body compression" apparatus as a means to restore effective blood volume and investigated its effectiveness in reducing ascites formation in cirrhotics in terms of its effect on parameters of ascites formation noted below. The subjects, eight cirrhotics with ascites and eight cirrhotics without ascites were given spironolactone (50–75 mg/day) and furosemide (40–80 mg/day) while they received a diet containing 85 mEq of sodium per day. All four limbs and the lower abdomen were compressed with constant pressure [height (cm) divided by 13.6 mmHg] once, for 3 h, using stroke rehabilitation splints, while patients lay supine. In cirrhotics both with and without ascites, urine volume, urinary sodium excretion, and creatinine clearance during the body compression were greater than values during control (non-compression) periods (urine volume, means 285 vs 169 ml/3 h; P < 0.001, urinary sodium excretion 15.8 vs 9.5mEq/3h; p < 0.001, creatinine clearance 74 vs 59 ml/min, P < 0.001, respectively). The increased basal plasma renin activity, angiotensin II, aldosterone, and norepinephrine levels in all cirrhotics were significantly decreased by the body compression. In another group of six cirrhotics who received no diuretics or albumin, repeat body compression alleviated ascites in three with well preserved renal function, but was ineffective in three with markedly impaired renal function. These results suggest that the improvement in renal function brought about by the body compression is attributable to an increase in effective circulating blood volume. This maneuver may be a useful complementary therapy in patients with cirrhotic ascites with well preserved renal function. (Received Jan. 12, 1998; accepted June 26, 1998)     

Renal function estimated from serum creatinine is overestimated in patients with rheumatoid arthritis because of their muscle atrophy

Abstract

We evaluated the reliability of serum creatinine concentration (Scr) to estimate renal function in patients with rheumatoid arthritis (RA). To quantify muscle volume (study 1) the lean body mass (LBM) in 25 women RA patients and 10 controls was measured using dual X-ray absorptiometry (DEXA). The 60-min creatinine clearance (Ccr60) and 60-min urinary excretion of creatinine (Ucr60) were also determined. The Ucr60 and LBM of the extremities, which were significantly correlated (r = 0.757, P < 0.0001), were lower in patients with long-standing and advanced RA than in controls. In study 2, the 24-h creatinine clearance (Ccr24) and 24-h urinary excretion of creatinine (Ucr24) were determined retrospectively in 82 women RA patients and 120 controls with normal Scr. The Ccr of long-standing and advanced RA patients was significantly lower than that of the controls, although the Scr of the long-standing RA patients was significantly lower than that of the advanced RA patients. The upper limit of the normal Scr for RA patients was calculated as being approximately 10% lower than that for controls. Thus, the renal function estimated from Scr may be overestimated in patients with long-standing and advanced RA because of their muscle atrophy.     

Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure

BACKGROUND/AIMS: C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples. RESULTS: Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v. 4.2 (0.4) pg/ml, respectively; p<0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p<0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (r=-0.56; p<0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2) v. 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p<0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours. CONCLUSIONS: Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.     

Comparison of renal resistive index among patients with Type 2 diabetes with different levels of creatinine clearance and urinary albumin excretion

Diabet. Med. 29, 1043–1046 (2012) Aim To evaluate the prevalence of increased renal resistive index and related factors among patients with Type 2 diabetes with different levels of creatinine clearance and urinary albumin excretion. Methods Laboratory analyses, including calculation of 24‐h urinary albumin excretion and 24‐h creatinine clearance, and renal doppler ultrasonography to measure renal resistive index, were carried out for patients newly diagnosed with Type 2 diabetes mellitus. Results Participants were classified into four groups according to 24‐h creatinine clearance and 24‐h urinary albumin excretion levels. Group 1 was composed of 73 patients (54.1%) with normal 24‐h creatinine clearance and 24‐h urinary albumin excretion. Group 2 was composed of 34 (25.2%) patients with normal 24‐h creatinine clearance and increased 24‐h urinary albumin excretion. Group 3 was composed of 14 (10.4%) patients with decreased 24‐h creatinine clearance and normal 24‐h urinary albumin excretion. Group 4 was composed of 14 (10.4%) patients with both decreased 24‐h creatinine clearance and increased 24‐h urinary albumin excretion . In total, 41 patients (30.4%) had increased renal resistive index levels. Comparison of the four groups with respect to increased renal resistive index revealed: among group 1 patients, 10 (13.7%) had increased renal resistive index levels; among group 2 patients, 14 (41.2%) had increased renal resistive index levels; among group 3 patients, eight (57.1%) had increased renal resistive index levels; among group 4 patients, nine (64.3%) had increased renal resistive index levels (P < 0.0001 for trend). In multivariate regression, 24‐h creatinine clearance (P < 0.0001), but not 24‐h urinary albumin excretion, was related to increased renal resistive index levels. Conclusion Renal resistive index levels were highest in patients with Type 2 diabetes with both decreased 24‐h creatinine clearance and increased 24‐h urinary albumin excretion, whereas they were lowest in patients with normal creatinine clearance and normal urinary albumin excretion.     

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.     

Effect of sulindac on prostaglandin excretion and renal function in cirrhotic patients with ascites

The effect of sulindac, a nonsteroidal anti-inflammatory drug, on renal prostaglandin synthesis and renal function variables was investigated in six cirrhotic patients with tense ascites and marked sodium retention. We studied serum thromboxane (TXB2) production, urinary prostaglandin excretion (6-keto-prostaglandin F1 alpha and TXB2) and renal function before and after administration of a therapeutic dose of sulindac (400 mg). After treatment, no significant changes were observed in urinary prostaglandin excretion, serum creatinine concentration, urine volume, or urinary sodium and creatinine clearance, whereas the serum TXB2 concentration was reduced in 89%. In five patients systemic prostaglandins were inhibited, but renal excretion remained unchallenged. However, one patient showed marked reduction of urinary prostaglandins associated with a depression of renal function. The study suggests that sulindac could be a safe substitute for other nonsteroidal anti-inflammatory drugs in cirrhotic patients with ascites. Further pharmacological trials seem to be warranted.     

Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites

Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.     

Urinary Prostaglandin E2 Excretion, Sodium Retention, and Diuretic Responsiveness in Patients with Chronic Liver Disease

It has been postulated that diminished renal prostaglandin E2 (PGE2) production, whether basal or in response to stimulation by diuretic treatment, determines the intensity of sodium retention in cirrhosis. Urinary PGE2 excretion (as an index of renal PGE2 production) as well as urine volume, urinary sodium and potassium excretion, and creatinine clearance were examined in 19 patients with cirrhosis and either no ascites, diuretic-responsive ascites, or diuretic-resistant ascites. Measurements were made both before (all patients) and after (ascitic patients) stimulation of renal PGE2 synthesis by 80 mg of furosemide intravenously. Urinary PGE2 excretion was similar in the three groups both before and after furosemide. Baseline urine volume and creatinine clearance were similar in all groups but were significantly less after furosemide in patients with diuretic-resistant ascites as compared to the other two groups. The natriuretic response to intravenous furosemide was significantly less in patients with diuretic-resistant ascites. Insertion of the peritoneovenous shunt to aid in the management of diuretic-resistant ascites resulted in a marked, immediate increase in urine volume and urinary PGE2 excretion in the four patients who were serially evaluated, but natriuresis occurred in only two. Overall, urinary PGE2 excretion correlated with urine volume but not with sodium excretion or creatinine clearance. Diminished renal PGE2 production, as reflected by urinary PGE2 excretion, does not appear to be a determinant of the severity of renal sodium retention in cirrhosis.     

High uric acid and urea clearance in cirrhosis secondary to increased “effective vascular volume”

Since urea and uric acid clearance are affected by the effective intravascular volume, we measured the fractional urea and uric acid excretion in cirrhosis. High urea and uric acid clearances were observed in 30 and 55 percent, respectively, of 20 consecutive cirrhotic patients with normal renal function. In seven patients with a high fractional uric acid excretion, 5 mg of isosorbide dinitrate every four hours for 24 hours induced a significant increase in the serum uric acid level (from 3.7 ± 0.8 mg/dl to 4.4 ± 0.8 mg/dl; <0.001) with a concomitant decrease in the fractional uric acid excretion (from 14.0 ± 3.2 percent to 8.8 ± 3.1 percent; <0.02). During the same test, the blood urea level increased from 3.3 ± 1.1 mmol/liter to 4.1 ± 1.2 mmol/liter (p < 0.005) with a decrease in fractional excretion from 51 ± 4.5 percent to 39 ± 5 percent (p < 0.001). The oral intake of sulfinpyrazone in six of these patients induced a normal uricosuric response. In two cirrhotic patients with ascites, 40 mg of furosemide associated with a 24-hour severe water restriction was also shown to normalize the high fractional excretion of both urea and uric acid. In nine patients with ascites, we observed a significant increase in blood urea and uric acid concentration despite the absence of change in creatinine clearance once ascites was removed by diuretics. On the basis of these findings, we believe that the high fractional excretion of both urea and uric acid frequently observed in cirrhosis is related to an increase in the effective vascular volume.     

Renal function estimated from serum creatinine is overestimated in patients with rheumatoid arthritis because of their muscle atrophy

We evaluated the reliability of serum creatinine concentration (Scr) to estimate renal function in patients with rheumatoid arthritis (RA). To quantify muscle volume (study 1) the lean body mass (LBM) in 25 women RA patients and 10 controls was measured using dual X-ray absorptiometry (DEXA). The 60-min creatinine clearance (Ccr60) and 60-min urinary excretion of creatinine (Ucr60) were also determined. The Ucr60 and LBM of the extremities, which were significantly correlated (r = 0.757, P < 0.0001), were lower in patients with long-standing and advanced RA than in controls. In study 2, the 24-h creatinine clearance (Ccr24) and 24-h urinary excretion of creatinine (Ucr24) were determined retrospectively in 82 women RA patients and 120 controls with normal Scr. The Ccr of long-standing and advanced RA patients was significantly lower than that of the controls, although the Scr of the long-standing RA patients was significantly lower than that of the advanced RA patients. The upper limit of the normal Scr for RA patients was calculated as being approximately 10% lower than that for controls. Thus, the renal function estimated from Scr may be overestimated in patients with long-standing and advanced RA because of their muscle atrophy. Received: March 17, 2000 / Accepted: July 14, 2000     

Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites.

We examined the acute effects of sinorphan, an inhibitor of enkephalinase, on plasma atrial natriuretic factor (ANF) and urinary sodium excretion in cirrhotic patients with ascites. A single oral dose of sinorphan (100 or 30 mg in 11 and 5 patients, respectively) was administered against placebo according to a double blind cross-over protocol. Basal plasma ANF levels varied over a large range between 2.6-79 pmol/L. Sinorphan, at a dose of 100 mg, inhibited 70% of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1.8 and 1.5 times basal values, respectively. There was a transient increase in sodium urinary output without a change in creatinine clearance over the initial 2-h period following drug administration. An increase in urinary cGMP was also observed on a longer period of 6 h. Plasma aldosterone decreased significantly, but the lowest concentration was reached 1 h later than the peak of plasma ANF. Mean blood pressure and PRA were unmodified. The effects of 30 mg sinorphan on plasma ANF, cGMP, and aldosterone were also significant, but less marked than those of the higher dose. Therefore, enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism. These results suggest that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascites.     

Renal function impairment induced by change in posture in patients with cirrhosis and ascites.

The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline.     

The effect of dietary sodium restriction on neurohumoral activity and renal dopaminergic response in patients with heart failure

BACKGROUND: This work evaluates the effect of a low-sodium diet on clinical and neurohumoral parameters and on renal dopaminergic system activity in heart failure (HF) patients. METHODS: We included 24 patients with mild-to-moderate stable HF with left ventricle ejection fraction <40%. Twelve patients were studied before and after a 15-day low-sodium diet; 12 maintained their usual diet. Serum sodium and creatinine, plasma l-DOPA, dopamine, its metabolites, BNP and aldosterone, and 24-h urinary sodium, creatinine, l-DOPA, dopamine and metabolites were measured. RESULTS: The two groups were matched respecting to demographic and clinical parameters. Low-sodium diet caused significant reductions in weight, 24-h urinary volume and sodium and sodium fractional excretion. Renal delivery of l-DOPA and urinary excretion of l-DOPA significantly decreased while dopamine and metabolites were not affected. Urinary dopamine/l-DOPA and urinary dopamine/renal delivery of l-DOPA ratios increased, plasma l-DOPA decreased and plasma dopamine increased. Plasma aldosterone slightly rose, BNP decreased and noradrenaline and adrenaline increased. NYHA functional class was not affected by sodium restriction. Controls showed no differences. CONCLUSIONS: These results suggest that sodium restriction leads to activation of antinatriuretic antidiuretic systems in HF patients. However, renal ability to synthesize dopamine is increased in this condition, probably as a counter-regulatory mechanism.     

Correlation between urinary activity of N-acetyl-β-d-glucosaminidase (NAG) and albumin excretion rate in type II (non-insulin-dependent) diabetic subjects

Summary Different kidney diseases are often associated with high urinary excretion of N-acetyl-β-D-glucosaminidase (NAG), a lysosomal enzyme involved in the breakdown of glycoproteins, whose activity is also increased in diabetic patients with poor metabolic control or vascular complications. In order to evaluate the relationship between renal function and urinary NAG levels in diabetes mellitus, 30 type II diabetic patients without evidence of kidney disease and 18 control subjects were studied. In each subject 24-h urinary excretion rates of NAG (fluorimetric method), albumin and β₂-microglobulin (radioimmunoassay), together with⁵¹Cr-EDTA clearance were performed. In diabetic patients urinary levels of NAG (356±25vs 162±9.2 nmol/h/mg creatinine, p<0.0001) and albumin (21±2.5vs 4.3±0.5 mg/24h, p<0.0001) were significantly higher than in the controls, while β₂-microglobulin levels and⁵¹Cr-EDTA clearance did not differ in the two groups. Moreover in diabetic patients NAG and albumin levels were positively and significantly correlated (r=0.63, p<0.001). These results suggest that urinary NAG excretion rate may be altered early in diabetic patients with apparently normal renal function; its diagnostic value seems to be similar to that of the albumin excretion rate.     

Dialytic Ultrafiltration by Hemofilter in Treatment of Patients with Refractory Ascites and Renal Insufficiency

Six cirrhotic patients with intractable ascites had coexisting renal insufficiency. Dialytic ultrafiltration of ascitic fluid by hemofilter was attempted in these patients for symptomatic relief. The hemofilter removes fluid and substances with a molecular weight less than 50,000 daltons and the concentrated ascitic fluid was reinfused into the peritoneal cavity after ultrafiltration. A transient increase in urine output (p less than 0.01), urinary sodium excretion (p less than 0.01), and endogenous creatinine clearance (p less than 0.02) was noted and the plasma creatinine levels had remained stable for more than 4 months after the procedure. Our study suggests that dialytic ultrafiltration of ascites by hemofilter is a safe method in the management of patients with refractory ascites and renal insufficiency.     

Effects of sodium intake, furosemide, and infusion of atrial natriuretic peptide on the urinary and metabolic clearances of arginine vasopressin in normal subjects

Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have important influences on water and electrolyte metabolism, and studies on the interactions between these hormones may have important implications. We have investigated the effects of sodium intake, furosemide, and infusion of ANP on the urinary and metabolic (nonurinary) clearances of AVP in hydrated normal subjects. On a high sodium diet there was an increase in urine volume, sodium excretion, osmolal clearance, plasma ANP concentration, and urinary clearance and fractional excretion of AVP, with a decrease in PRA. The infusion of furosemide increased urine volume, sodium excretion, osmolal clearance, and PRA, but decreased circulating ANP levels and urinary clearance and fractional excretion of AVP. Since there was a positive correlation between circulating ANP and urinary clearance of AVP in these experiments, we infused human alpha ANP in physiological amounts and found increases in the urinary and metabolic (nonurinary) clearances of AVP. The changes in urinary clearance of AVP in all three experiments occurred even in relation to creatinine clearance. These observations demonstrate that urinary clearance of AVP does not correlate with urine volume, sodium or solute excretion, or PRA. The observations support a physiological role for ANP in modulating the renal action of AVP, probably at the level of the renal tubules, and indicate a need for caution when using plasma or urinary AVP as an indicator of AVP release from the neurohypophysis.     

Assessment of Intestinal Permeability and Absorption in Cirrhotic Patients with Ascites Using Combined Sugar Probes

Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects, cirrhotic patients with ascites have abnormal intestinal permeability, measured by urinary lactulose/rhamnose excretion, and normal small intestinal absorption, assessed by the urinary rhamnose/3-O-methyl-D-glucose ratio. Low urine recovery of sugar probes found in cirrhotic patients appears to be the result of nonintestinal factors affecting clearance rather than reduced intestinal absorption.