Strict volume control in the treatment of nephrogenic ascites
Ali Ihsan Gunal1,,
Ilgin Karaca2,
Huseyin Celiker1,
Erdogan Ilkay2 and
Soner Duman1
1 Department of Nephrology and
2 Department of Cardiology, Firat University Medical School, Elazig, Turkey
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Abstract
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Background. Nephrogenic ascites refers to the condition of refractory ascites of unknown aetiology and occurs mainly in patients with end-stage renal disease who are undergoing haemodialysis. Despite many treatment modalities, nephrogenic ascites remains difficult to control and has a poor prognosis.
Methods. We investigated six such patients who had developed severe, apparently refractory ascites during haemodialysis. They all had seriously disturbed cardiac dimensions and function. They were treated with repeated isolated ultrafiltration and severe salt restriction, while their cardiac functions were monitored with echocardiography.
Results. After a mean of 18±4 l of fluid per patient was removed in 27±8 days, ascites disappeared in all patients. Blood pressure and cardiothoracic indices were decreased from 130±20/83±10 to 95±11/60±6 mmHg (P<0.02) and from 0.61±7 to 0.47±5 (P<0.02), respectively. At the end of treatment, heart rates had decreased from 102±10 to 85±6 beats/min. Previously increased left atrial diameters, end-systolic and end-diastolic dimensions of the left ventricles, and right ventricular diameters reached normal values. Ejection fractions initially decreased in all patients, and then increased slightly to markedly after treatment.
Conclusion. Nephrogenic ascites is a component of right-sided cardiac congestion mediated by volume overload, and it should be treated with severe salt restriction and frequent ultrafiltration with haemodialysis and, if that fails, with daily isolated ultrafiltration.
Keywords: echocardiography; heart; nephrogenic ascites; salt restriction; ultrafiltration
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Introduction
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Nephrogenic ascites is a well-recognized complication of maintenance haemodialysis therapy. Although the pathogenesis of ascites remains elusive, several factors have been considered, including: elevated hepatic venous hydrostatic pressure, fluid retention, increased peritoneal membrane permeability secondary to uraemic toxins, reninangiotensin activation, circulating immune complexes, haemosiderosis and impaired lymphatic drainage [1]. A variety of treatment modalities have been attempted, including: ultrafiltration during haemodialysis [2,3], isolated ultrafiltration [4], intraperitoneal steroid instillation [5], repeated paracentesis with or without intravenous reinfusion of ascites fluid [6], LeVeen shunt [7], nephrectomy [8], angiotensin-converting enzyme inhibitors [9], maintenance peritoneal dialysis [10] and renal transplantation [2]. Nevertheless, the condition of nephrogenic ascites remains difficult to control and has a poor prognosis. The reported survival of patients who have it ranges from 7 to 10.7 months. Of those patients, one-third develop severe cachexia and 44% die within 15 months [11].
We report here the successful application of repeated, isolated ultrafiltration and severe salt restriction in the treatment of six patients suffering from nephrogenic ascites.
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Subjects and methods
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Six patients (three men and three women between 42 and 62 years of age) who presented with ascites of varying severity were included the study. All of the patients had been dialysed at another center prior to this study. The mean time on dialysis was 32±15 months (range 1050). The duration of ascites was 6.5±2.4 months (range 310). The mean interdialytic weight gain of the patients prior to the study was 4.6±0.5 kg (range 4.05.5), which suggested their non-compliance with salt restriction. All of the patients had a history of hypertension. Patients 1 and 2 were taking antihypertensive medications (including the combination of angiotensin-converting enzyme inhibitors plus calcium antagonist and doxazosin, respectively) prior to the study with no effect. At the time of presentation, all patients had tense ascites on physical examination. Distended neck veins were present in all patients. Pretibial oedema was present only in patient 5. None had any stigmata of chronic liver disease. Two patients had pulmonary rales. The examination of the heart in four patients revealed variable degrees of systolic murmurs consistent with mitral insufficiency. All patients had cachexia to variable degrees. Abdominal ultrasonography confirmed large amounts of ascitic fluid, but no intra-abdominal or retroperitoneal abnormalities except small kidneys. Chest X-rays revealed cardiac enlargement in all patients and a small right-sided pleural effusion in one. Liver function tests were not consistent with hepatic disease in any of the patients.
Treatment schedule
All patients were admitted to the hospital to ensure better salt restriction with a diet containing <100 mmol/day sodium chloride. In this way, we lowered the interdialytic weight gain to <1 kg. With lowered interdialytic weight gain, a large volume of fluid could be removed by ultrafiltration without producing hypotensive episodes. Haemodialysis was performed for 4 h three times weekly. In the beginning, daily ultrafiltration was done with or without dialysis. If hypotension occurred, on the days of conventional haemodialysis isolated ultrafiltration was initiated to the extent that could be tolerated by the patients, followed by conventional haemodialysis without ultrafiltration. On the days when conventional haemodialysis was not performed, isolated ultrafiltration was applied. The duration and volume of isolated ultrafiltration varied between the patients. Times ranged from 4 to 7 h to remove 1 l of water after the hypotension occurred. A bicarbonate dialysate containing 135 mmol/l Na and 3 mEq/l Ca was used. A polysulfone dialyser (1.2 m2 surface area) (F6; Fresenius Company, Germany) was used. Blood flow was 250300 ml/min, dialysate flow was 500 ml/min. Ultrafiltration was controlled volumetrically in all haemodialysis machines used in this study.
Chest radiographs were obtained at the beginning and end of the study and the cardiothoracic index (CTI) was calculated according to established methods.
Echocardiographic examination was performed using an ATL-Ultramark 9 ultrasonoscope with 2.5 MHz transducer, according to the recommendations of the American Society of Echocardiography [12]. An experienced echocardiographer who was blinded to the study design made all measurements. Echocardiography could not be performed on patient 6. Repeated measurements were done in all patients. The results obtained before and after the treatment are presented below and in the tables. Left ventricular mass index (LVMI) was calculated using the following equation:

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The Ethics Committee of The Firat University Hospital approved the study design. Informed consent was obtained from every patient.
Statistical analysis
The Wilcoxon signed rank test was used for statistical analysis. All data are given as mean±SD. P<0.05 was considered significant.
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Results
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Some clinical data and echocardiographic measurements before the initiation of ultrafiltration treatments are given in Table 1
. Patients 1 and 2 had elevated blood pressures. CTI exceeded 0.50 in all patients. Increased left ventricular wall thickness, mass index and chamber size, suggesting long standing pressure and volume overload, were present in all patients. All patients had variable degrees of mitral valve regurgitation on colour flow examination. After the treatment, regurgitation disappeared in all patients. No patient had pericardial effusion.
After a mean of 18±4 l of fluid was removed over 27±8 days, ascites disappeared in all patients. Blood pressure and CTI decreased from 130±20/83±10 to 95±11/60±6 mmHg (P<0.02) and from 0.61±7 to 0.47±5 (P<0.02), respectively (Table 2
). At the end of the treatment, heart rates decreased significantly from 102±10 to 85±6 beats/min, suggesting amelioration of cardiac function (Table 2
).
The main echocardiographic parameters at the beginning and at the end of the intensified treatment are presented in Table 2
. The left atrial diameter was markedly increased in all subjects. After treatment, these values reverted to normal in patients 1, 2, 3 and 4, and significantly decreased in patient 5. The end-systolic and end-diastolic dimensions of the left ventricles and the right ventricular diameters reverted to normal values. Ejection fraction, which was decreased in all patients, increased post-treatment slightly to markedly, but not always up to normal. Peak flow velocities of the early (E) and late (A) diastolic fillings and their ratios were used in the assessment of left ventricular diastolic performance. A remarkable finding was that the E/A ratios often were within normal limits, erroneously suggesting normal diastolic function of the left ventricles. This probably resulted from elevated atrial pressures, causing an increase in the E values. At the end of the treatment, when the elevated left atrial pressure decreased, the E/A ratios dropped to low pathologic levels.
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Discussion
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Nephrogenic ascites remains a poorly understood complication of long-term haemodialysis. Before the diagnosis of nephrogenic ascites is established, other causes of peritoneal fluid accumulation, such as cirrhosis, abdominal malignancy, pericardial constriction or tamponade, inferior vena caval obstruction, tuberculous peritonitis and pancreatitis, must be ruled out [13].
The most important finding of our study is that all patients had marked volume overload, suggesting that their ascites was a component of right-sided cardiac congestion. This was confirmed by the fact that it could be resolved with improved volume control. Volume reduction was not easy, however, because ultrafiltration was badly tolerated as the patients had severely damaged hearts. It was essential, therefore, above all to prevent excessive interdialytic weight gain using severe salt restriction. As it is clear that the cardiac condition of our patients was the result of a long-standing process, one may speculate about the pathophysiology leading to it. Most probably, this starts with fluid retention, increase in blood volume, end diastolic pressure and cardiac output, leading to some cardiac dilatation and hypertension in accordance with the autoregulation theory. With further increases in preload, end-diastolic volume could rise to such high levels that the contractility and the shortening capacity of the myocardial fibres will suffer. At this stage, effective stroke volume decreases and previously elevated blood pressure will decrease. Indeed, at their initial examinations our patients had increased pulse rates, cardiac chamber sizes and depressed ejection fractions, suggesting seriously disturbed hearts brought about by excess fluid retention. After a mean weight loss of 18 kg, pulse rates, cardiac chamber sizes and ejection fractions were nearly normalized and ascites disappeared.
It is not clear why the retained fluid in our patients preferentially accumulated in the abdominal cavity. In keeping with reports in the literature, most of our patients had no visible oedema, despite elevated venous pressures. The formation of ascites is a dynamic process dependent upon factors influencing the formation and resorption of the fluid. In the case of increased systemic venous pressure, the rate of formation of ascites is increased due to elevated hepatic and peritoneal (caval) venous pressures. Resorption of ascitic fluid into the circulation occurs predominately via lymphatic channels. It has been shown [14] that lymphatic drainage of the peritoneum is impaired in nephrogenic ascites, while general lymphatic flow is strongly increased. This impairment may be due to elevated venous pressure at the juncture at which the lymphatic channels are drained.
In one study [11], which used different treatment modalities including paracentesis, fluid and sodium restriction, and aggressive intradialytic ultrafiltration or additional isolated ultrafiltration, a total reversal or a significant reduction of ascites could be achieved in 50% of the patients. In our study, ascites disappeared in all patients after intensified ultrafiltration and even stricter salt restriction. Similar results were obtained by Shin et al. [4] and Toz et al. [15]. In a recent study, Han et al. [3] showed that daily haemodialysis was effective in controlling ascites in
78% of the patients. The reason that many physicians fail to remove sufficient fluid from patients with nephrogenic ascites is probably that those patients are particularly prone to developing hypotension during ultrafiltration. When this happens, ultrafiltration is discontinued and intravenous fluid may be required to maintain blood pressure. This results in inadequate removal of excess fluid, and control of ascites is not achieved. We have shown that correction of volume overload is possible provided this is done carefully and with perseverance. Because the hearts of our patients proved to be severely damaged, ultrafiltration should be performed in small steps but frequently. This allows the heart to adapt gradually to the decreasing volume load. It is well known that ultrafiltration is better tolerated when it is performed separately, because the osmotic and electrolyte shifts resulting from dialysis are absent. It is also clear that severe salt restriction will be most helpful, for it reduces the need to remove large amounts of fluid in a short time.
Perhaps the most important finding of our study is that remodeling of the dilated heart is possible and is probably the crucial factor in the relief of this condition. In view of the favourable response of our patients with nephrogenic ascites to intensified ultrafiltration, the role of previously mentioned treatment modalities such as intraperitoneal steroids, nephrectomy or LeVeen shunt may need to be re-evaluated. Of course there are going to be patients who will be refractory to the proposed treatment, but this refractoriness is demonstrated if the method described by us fails; so far we have not encountered such cases.
In conclusion, before resorting to more invasive therapeutic procedures, attention should be paid to enforcing sodium restriction and an attempt should be made to remove excess fluid with frequent ultrafiltration with haemodialysis and, if that is unsuccessful, with daily isolated ultrafiltration, preferably under echocardiographic control.
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Acknowledgments
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We thank Dr Evert J. Dorhout Mees for his critical comments on reviewing the manuscript.
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Notes
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Correspondence and offprint requests to: Dr Ali
hsan Günal, Firat Üniversitesi Tip Fakültesi, Nefroloji Bilim Dali, 23200 Elazig, Turkey. Email: igunal{at}yahoo.com 
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Received for publication: 26. 7.01
Accepted in revised form: 28. 1.02