Characterization of Renal Prostaglandin E Responsiveness in Decompensated Cirrhosis: Implications for Renal Sodium Handling

1982 ◽  
Vol 63 (6) ◽  
pp. 555-563 ◽  
Author(s):  
Murray Epstein ◽  
Meyer Lifschitz ◽  
M. Ramachandran ◽  
Kenneth Rappaport
Keyword(s):  
Renal Function ◽  
Water Immersion ◽  
Normal Subjects ◽  
Decompensated Cirrhosis ◽  
Prostaglandin E ◽  
Prostaglandin Synthase ◽  
Endogenous Prostaglandins ◽  
Cirrhotic Patients ◽  
Renal Sodium Handling ◽  
Sodium Handling

1. It has been suggested that endogenous renal prostaglandin E (PGE) constitutes a determinant of renal haemodynamics and renal sodium handling in patients with cirrhosis. We have accordingly assessed the effects of augmenting endogenous prostaglandins on renal function. We utilized water immersion to the neck since previous studies demonstrated that the redistribution of blood volume and concomitant central hypervolaemia thus induced produces a prompt and marked augmentation of PGE excretion in normal man. 2. Thirteen cirrhotic patients were studied twice while in balance on a daily 10 mmol of sodium/100 mmol of potassium diet during control and during water immersion. Urinary PGE was determined hourly for 6 h. 3. Cirrhotic patients manifested a wide continuum of responses characterized by either a sluggish or barely discernible natriuretic response (n = 5) or an appropriate natriuretic response (n = 8). 4. Water immersion to the neck resulted in a highly significant increase in mean UPGEV, which was threefold that manifested by normal subjects studied under identical conditions. Furthermore, cumulative sodium excretion during immersion correlated with PGE excretion (P < 0·05). 5. These findings, together with the results of studies utilizing prostaglandin synthase inhibitors, are consistent with the postulate that renal PGE may play a role in the alterations of renal function in decompensated cirrhosis.

Dissociation of Renin-Aldosterone and Renal Prostaglandin E during Volume Expansion Induced by Immersion in Normal Man

1980 ◽  
Vol 59 (1) ◽  
pp. 55-62 ◽  
Author(s):  
M. Epstein ◽  
M. D. Lifschitz ◽  
R. Re ◽  
E. Haber
Keyword(s):  
Plasma Renin Activity ◽  
Volume Expansion ◽  
Water Immersion ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Plasma Aldosterone ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Plasma Aldosterone Concentration ◽  
Normal Man

1. The relationship of the renin-angiotensin-aldosterone axis with renal prostaglandin E is complex. Although studies have suggested that these two hormonal systems respond to experimental manipulations in a parallel manner, their interdependence has not been assessed fully during volume expansion. Since studies have demonstrated that in normal man the central hypervolaemia induced by water immersion to the neck produces a prompt and profound suppression of plasma renin activity and plasma aldosterone concentration without concomitant alteration of plasma composition, immersion afforded a unique opportunity to assess simultaneously the effects of central hypervolaemia on plasma renin activity, plasma aldosterone concentration and prostaglandin E excretion. 2. Seven normal subjects were studied twice while in balance on a diet containing 10 mmol of sodium/day, 100 mmol of potassium/day: with indomethacin administration (50 mg given every 6 h for five doses) and without indomethacin. Urinary prostaglandin E excretion was measured hourly and plasma renin activity and plasma aldosterone concentration at 30 min intervals. 3. Immersion was associated with a marked suppression of plasma renin activity (59 ± 7%) and plasma aldosterone concentration (55 ± 3%) with a return to pre-study values during the recovery hour. Concomitantly, urinary prostaglandin E excretion increased from 4.7 to a peak of 10.9 ng/min. Although administration of indomethacin lowered the basal rate of urinary prostaglandin E excretion and plasma renin activity, it did not prevent the subsequent augmentation of urinary prostaglandin E or the suppression of plasma renin activity and plasma aldosterone during the subsequent 4 h of immersion. 4. These results demonstrate a dissociation of renin-aldosterone and prostaglandin E during hypervolaemia and suggest that whereas prostaglandin E may constitute one of the major determinants of renin release clinically and experimentally, these two hormonal systems can be dissociated from each other in response to central volume expansion in man.

Prostaglandin precursor fatty acids in cirrhosis with ascites: Effect of linoleic acid infusion in functional renal failure

1988 ◽  
Vol 74 (6) ◽  
pp. 613-619 ◽  
Author(s):  
Antoni Rimola ◽  
Pere Ginés ◽  
Eulàlia Cusó ◽  
Jordi Camps ◽  
Joan Gaya ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Normal Subjects ◽  
Serum Levels ◽  
Acid Deficiency ◽  
Cirrhotic Patients ◽  
Arachidonic Acids

1. Functional renal failure (FRF) in cirrhosis with ascites could be related to an inappropriately low renal prostaglandin (PG) production. To investigate whether the impaired renal PG synthesis in these patients is related to a PG precursor fatty acid deficiency, serum levels of linoleic and arachidonic acids and the urinary excretion of PGE2, 6-keto-PGF1α and thromboxane B2 (TxB2) were measured in 10 normal subjects, 17 non-azotaemic cirrhotic patients with ascites and 10 cirrhotic patients with ascites and FRF. 2. Serum linoleic acid levels were similar in the three groups studied. Both groups of cirrhotic patients showed lower arachidonic acid levels than normal subjects; however, non-azotaemic cirrhotic patients and patients with FRF did not differ in relation to serum arachidonic acid. 3. Non-azotaemic cirrhotic patients had higher urinary PGE2, 6-keto-PGF1α and TxB2 excretion than normal subjects and cirrhotic patients with FRF. Patients with FRF showed similar urinary PGE2 and TxB2 and lower urinary 6-keto-PGF1α than normal subjects. In all cirrhotic patients no significant correlation was found between serum linoleic and arachidonic acid levels and urinary PGs. 4. In seven patients with FRF an acute intravenous infusion of linoleic acid induced a marked increase in serum levels of this fatty acid. However, no increase in serum arachidonic acid levels and urinary PG excretion and no improvement in renal function was observed. 5. This study suggests that an arachidonic acid deficiency is present in cirrhotic patients with ascites but that this abnormality is not a major determinant of renal function and PG production in these patients. Acute intravenous administration of linoleic acid is not associated with any change in renal PG production and renal function in cirrhotic patients with FRF.

Identification of diuretic non-responders with poor long-term clinical outcomes: a 1-year follow-up of 176 non-azotaemic cirrhotic patients with moderate ascites

2011 ◽  
Vol 121 (11) ◽  
pp. 509-521 ◽  
Author(s):  
Ying-Ying Yang ◽  
Han-Chieh Lin ◽  
Ming-Wei Lin ◽  
Chi-Jen Chu ◽  
Fa-Yauh Lee ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Basal Plasma ◽  
Cirrhotic Patients ◽  
Plasma Aldosterone Level ◽  
Renal Sodium Handling ◽  
Sodium Handling

In cirrhosis, the development of ascites and the response to diuretics are determined by the RAAS (renin–angiotensin–aldosterone system) and renal sodium handling system. We hypothesized that SNPs (single nucleotide polymorphisms) affecting candidate genes in the RAAS and renal sodium handling pathway may influence initial diuretic responsiveness and affect clinical outcome in non-azotaemic cirrhotic patients with moderate ascites. We prospectively recruited 176 patients and 245 controls and determined their genetic polymorphisms for 24 SNPs of ten genes involved in the RAAS and renal sodium handling pathway. In cirrhotic patients with moderate ascites, multivariate analysis showed that diuretic unresponsiveness was predicted by a high basal plasma aldosterone level, by a high aldosterone/renin ratio and by specific risk genotypes of ACE (gene encoding angiotensin-converting enzyme), CYP11B2 (gene encoding aldosterone synthase) and ADDA (gene encoding α-adducin). This association between genetic polymorphisms and diuretic unresponsiveness was confirmed by an independent validation cohort. Notably, additive effects in relation to diuretic unresponsiveness were observed in cases where there was the simultaneous presence of the three risk genotypes. Among patients carrying any of the risk genotypes, more episodes of paracentesis and ascites-related readmission after 3 months of treatment, as well as a reduced 1-year survival rate, were observed. In addition to traditional predictors, our present study provides additional genetic and neurohormonal predictors that will help to identify diuretic non-responders among cirrhotic patients with moderate ascites. Among those carrying unfavourable risk genotypes, additional therapies, including paracentesis and albumin infusion, should be started as early as possible.

Relationship between Urinary Kallikrein and Renal Sodium Handling during Water Immersion in Normal Man*

1980 ◽  
Vol 50 (1) ◽  
pp. 122-127 ◽  
Author(s):  
MURRAY EPSTEIN ◽  
RICHARD A. STONE ◽  
ARTHUR G. DENUNZIO ◽  
RONALD P. FRIGON
Keyword(s):  
Water Immersion ◽  
Urinary Kallikrein ◽  
Normal Man ◽  
Renal Sodium Handling ◽  
Sodium Handling
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