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Albumin substitution improves urinary sodium excretion and diuresis in patients with liver cirrhosis and refractory ascites
Journal ofHepatology 1999; 31: 1132 Printed in Denmark . AN rights reserved Munksgaard Copenhagen
Copyright 0 European Association for the Study of the Liver 1999
Journal of Hepatology ISSN 0168-8278
Correspondence
Albumin substitution improves urinary sodium excretion and diuresis in patients with liver cirrhosis and refractory ascites To the Editor:
We read with interest the recent article by Gentilini et al. (1) and the editorial by Blendis & Wong (2) showing for the first time in a controlled and randomized study the beneficial effect of albumin infusions on the response to diuretics in patients with cirrhosis of the liver and ascites. The authors postulate that plasma expansion in these patients with a reduced effective arterial blood volume is the major cause of improved diuretic response. Interestingly, the cost/ benefit ratio was in favour of the albumin-treated group, despite the high costs of albumin infusions. Our own experience not only supports these findings but shows for the tirst time that albumin substitution in addition to diuretic therapy may normalize urinary sodium excretion in patients with refractory ascites (3) and cirrhosis of the liver. In a pilot study we treated 12 patients with refractory ascites (7 with alcoholic and 5 with non-alcoholic cirrhosis) with high doses of albumin (mean 22.1 g/die) in order to improve the response to diuretic therapy and to reduce the amount of diuretics needed to achieve a negative sodium balance. All patients suffered from intractable diuretic ascites. Our aim was to improve renal perfusion in patients awaiting orthotopic liver transplantation because unfortunately waiting time can be up to 15 months and even longer, so that central arterial volume depletion due to (mainly) loop diuretics not infrequently results in preoperative renal failure. Furthermore, renal function parameters are the most powerful preoperative predictors of survival after liver transplantation (4). As the patients in our pilot study were to be transplanted, we did not include bed rest in our treatment regime because it would induce a reduction of muscle mass. In fact, pretransplant body mass is an important predictor of transplantation outcome.
TABLE 1 Renal function parameters (n= 12) before and after treatment’
Serum albumin (g/dl) Serum creatinine (mg/dl) Serum sodium (mmol/l) Serum potassium (mmol/l) Creatinine clearance (mVmin) Urine volume/die (ml/die) Urine sodium excretion (mmol/die) Bodyweight (kg) *p
1132
Before treatment
After treatment
2.8kO.49 0.8920.26 134.353.7 3.920.4 93.9528.3 720?230 48.7k71.4 77213.2
4.2?0.66* 1.020.27 135.722.1 4.220.34 89.2k20.2 1265+238* 109?29.5** 66.9?15.1*
Our main findings were a significantly better urinary sodium excretion, with normalization in some cases and an increase in urine volume (Table 1). At the same time, the amounts of diuretics necessary to resolve ascites were less than in the medication before admission. Albumin was substituted for a mean period of 31 days, a maintenance dosage being given during the last mean 10 days according to the plasma concentration of albumin. The complication rate of diuretic ascites therapy ranges from ll-71% (5,6). Thus, it is worth mentioning that in our small pilot study on patients with refractory ascites we were able to dismiss furosemide from the daily medication in all cases but one. Furthermore, the average spironolactone dose could be reduced from 222283 to 133290 mg/die. The mean amount of furosemide before and after albumin treatment was 32223 mg and 52 17 mg, respectively. Xipamid was given in a mean dosage of 7?16 mg and 19-C19 mg before and after the hospital stay. Diuretics could even be discontinued in one case. One patient did not respond with increased diuresis, although he maintained a stable body weight without any diuretics. Two patients have been transplanted meanwhile. We agree with Prof. Gentilini and his coworkers and with Prof. Blendis that further trials are necessary to determine which subgroups will best benefit from the option of albumin infusions. Indeed, patients with a history of long-term intake of loop diuretics such as furosemide might profit most from this treatment.
Christian Schindler and Guiliano Ramadori
Division of Gastroenterology and Endocrinology, University of Giittingen, Robert-Koch-StraJe 40, 37075 Giittingen. Germany
References 1. Gentilini P Casini-Raggi V, Di Fiore G, Romanelli RG, Buzzelli G, Pinzani M, et al. Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. J Hepatol 1999; 30: 63945. 2. Blendis L, Wong F. Intravenous albumin with diuretics: protean lessons to be learnt? J Hepatol 1999; 30: 727-30. 3. Arroyo V, Gin& E Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology 1996; 23: 164-76. 4. Gonzalez E, Rimola A, Navasa M, Andreu H, Grande L, GarciaValdecasas J-C, et al. Liver transplantation in patients with nonbiliary cirrhosis: prognostic value of preoperative factors. J Hepatol 1998; 28: 320-8. 5. Sherlock S, Senewiratne B, Scott A, Walker JG. Complications of diuretic therapy in hepatic cirrhosis. Lancet 1966; i: 1049-52. 6. Ginbs P Arroyo V, Rod&s J. Pharmacotherapy of ascites associated with cirrhosis. Drugs 1992; 43: 31632.
Copyright 0 European Association for the Study of the Liver 1999
Journal of Hepatology ISSN 0168-8278
Correspondence
Albumin substitution improves urinary sodium excretion and diuresis in patients with liver cirrhosis and refractory ascites To the Editor:
We read with interest the recent article by Gentilini et al. (1) and the editorial by Blendis & Wong (2) showing for the first time in a controlled and randomized study the beneficial effect of albumin infusions on the response to diuretics in patients with cirrhosis of the liver and ascites. The authors postulate that plasma expansion in these patients with a reduced effective arterial blood volume is the major cause of improved diuretic response. Interestingly, the cost/ benefit ratio was in favour of the albumin-treated group, despite the high costs of albumin infusions. Our own experience not only supports these findings but shows for the tirst time that albumin substitution in addition to diuretic therapy may normalize urinary sodium excretion in patients with refractory ascites (3) and cirrhosis of the liver. In a pilot study we treated 12 patients with refractory ascites (7 with alcoholic and 5 with non-alcoholic cirrhosis) with high doses of albumin (mean 22.1 g/die) in order to improve the response to diuretic therapy and to reduce the amount of diuretics needed to achieve a negative sodium balance. All patients suffered from intractable diuretic ascites. Our aim was to improve renal perfusion in patients awaiting orthotopic liver transplantation because unfortunately waiting time can be up to 15 months and even longer, so that central arterial volume depletion due to (mainly) loop diuretics not infrequently results in preoperative renal failure. Furthermore, renal function parameters are the most powerful preoperative predictors of survival after liver transplantation (4). As the patients in our pilot study were to be transplanted, we did not include bed rest in our treatment regime because it would induce a reduction of muscle mass. In fact, pretransplant body mass is an important predictor of transplantation outcome.
TABLE 1 Renal function parameters (n= 12) before and after treatment’
Serum albumin (g/dl) Serum creatinine (mg/dl) Serum sodium (mmol/l) Serum potassium (mmol/l) Creatinine clearance (mVmin) Urine volume/die (ml/die) Urine sodium excretion (mmol/die) Bodyweight (kg) *p
1132
Before treatment
After treatment
2.8kO.49 0.8920.26 134.353.7 3.920.4 93.9528.3 720?230 48.7k71.4 77213.2
4.2?0.66* 1.020.27 135.722.1 4.220.34 89.2k20.2 1265+238* 109?29.5** 66.9?15.1*
Our main findings were a significantly better urinary sodium excretion, with normalization in some cases and an increase in urine volume (Table 1). At the same time, the amounts of diuretics necessary to resolve ascites were less than in the medication before admission. Albumin was substituted for a mean period of 31 days, a maintenance dosage being given during the last mean 10 days according to the plasma concentration of albumin. The complication rate of diuretic ascites therapy ranges from ll-71% (5,6). Thus, it is worth mentioning that in our small pilot study on patients with refractory ascites we were able to dismiss furosemide from the daily medication in all cases but one. Furthermore, the average spironolactone dose could be reduced from 222283 to 133290 mg/die. The mean amount of furosemide before and after albumin treatment was 32223 mg and 52 17 mg, respectively. Xipamid was given in a mean dosage of 7?16 mg and 19-C19 mg before and after the hospital stay. Diuretics could even be discontinued in one case. One patient did not respond with increased diuresis, although he maintained a stable body weight without any diuretics. Two patients have been transplanted meanwhile. We agree with Prof. Gentilini and his coworkers and with Prof. Blendis that further trials are necessary to determine which subgroups will best benefit from the option of albumin infusions. Indeed, patients with a history of long-term intake of loop diuretics such as furosemide might profit most from this treatment.
Christian Schindler and Guiliano Ramadori
Division of Gastroenterology and Endocrinology, University of Giittingen, Robert-Koch-StraJe 40, 37075 Giittingen. Germany
References 1. Gentilini P Casini-Raggi V, Di Fiore G, Romanelli RG, Buzzelli G, Pinzani M, et al. Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. J Hepatol 1999; 30: 63945. 2. Blendis L, Wong F. Intravenous albumin with diuretics: protean lessons to be learnt? J Hepatol 1999; 30: 727-30. 3. Arroyo V, Gin& E Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology 1996; 23: 164-76. 4. Gonzalez E, Rimola A, Navasa M, Andreu H, Grande L, GarciaValdecasas J-C, et al. Liver transplantation in patients with nonbiliary cirrhosis: prognostic value of preoperative factors. J Hepatol 1998; 28: 320-8. 5. Sherlock S, Senewiratne B, Scott A, Walker JG. Complications of diuretic therapy in hepatic cirrhosis. Lancet 1966; i: 1049-52. 6. Ginbs P Arroyo V, Rod&s J. Pharmacotherapy of ascites associated with cirrhosis. Drugs 1992; 43: 31632.