Case Rep Nephrol Urol 2012;2:138–144
DOI: 10.1159/000343247

Published online:© 2012 S. Karger AG, Basel
September 24, 2012 ISSN 1664–5510
www.karger.com/cru

This is an Open Access article licensed under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/OA-license), applicableto the online version of the article only. Distribution for non-commercial purposes only.

A Case of Cell-Free andConcentrated Ascites
Reinfusion Therapy Effective
for Refractory Ascites in
Spontaneous Bacterial
Peritonitis in a Renal
Transplant Patient
Atsuhiro Maedaa Kazuhito Takedaa Kazuhiko Tsuruya b
Shuuhei Miura a Jirou Toyonaga a Satsuki Nakashitaa
Masahide Furushou a Hideyuki Mukai a
Yoshiharu Mutou a Tomo Komaki a Keita Takae a
Chikao YasunagacaDepartment of Nephrology and Kidney Center, Aso-Iizuka Hospital, Iizuka,
Department of Medicine and Clinical Science, Graduate School of Medical
Sciences, Kyushu University, Fukuoka, and cDepartment of Kidney Center,
Saiseikai Yahata General Hospital, Kitakyushu, Japanb

Key Words
Acute renal failure · Cell-free and concentrated ascites reinfusion therapy · Refractory
ascites · Renal transplantation · Spontaneous bacterial peritonitis

Abstract
A 58-year-old Japanese male with chronic hepatitis C underwent kidney transplantation froman unrelated donor in October 1998. In December 2004, the patient was admitted for
spontaneous bacterial peritonitis (SBP). Abdominal paracentesis and albumin transfusion
were performed, but control of ascites was poor. A randomized, controlled study of patientswith SBP showed that patients receiving cefotaxime with a high-volume albumin transfusion(50–75 g/50 kg) were significantly less likely to have irreversible renal failure and had lower
mortality. Japan, however, relies on imports for 70% of its albumin formulations, which
complicates high-volume albumin transfusion. Consequently, albumin transfusion is often
limited to single treatments in the range of only 25 g (25%, 100 ml). A single cell-free andconcentrated ascites reinfusion therapy (CART) treatment can reinfuse approximately 60 g ofAtsuhiro Maeda

Department of Nephrology and Kidney Center
Aso-Iizuka Hospital
3-83 Yoshio-Machi, Iizuka 820-8505 (Japan)
E-Mail maedaatuhiro @mopera.net

138

Case Rep Nephrol Urol 2012;2:138–144
DOI: 10.1159/000343247

Published online:© 2012 S. Karger AG, Basel
September 24, 2012 ISSN 1664–5510
www.karger.com/cru

albumin, corresponding to a high-volume albumin transfusion capable of reducing theassociated risk of infection or allergic reaction. Though this case was an SBP patient, after
the ascites were found to be negative for endotoxins, CART was performed, and control ofascites was achieved without observation of fever, hypotension, or other adverse effects.
CART provides greater supplementation of albumin than albumin transfusion and can be aneffective modality of treatment for hypoalbuminemia in SBP patients if ascites are negativefor endotoxins.

Introduction
Refractory ascites causes abdominal distention, abdominal pain and dyspnea andthereby aggravates patient quality of life and activities of daily living. The effect of
abdominal paracentesis is temporary, but loss of albumin and globulin can cause
deterioration of nutritional and immune status and lowered colloid osmotic pressure.
Cell-free and concentrated ascites reinfusion therapy (CART) is a treatment which
maintains albumin and globulin by filtration, concentration, and reinfusion of drained
ascites. The advantages of this method are that albumin transfusion can be employedsparingly, and the risk of infection or allergic reaction is thus reduced. However, CART
is dangerous to spontaneous bacterial peritonitis (SBP) patients because inadvertent
reinfusion of filtrated, concentrated endotoxins in ascites has caused adverse effects of
temporary fever and shock.
We report our pursuit of CART for refractory ascites in SBP after finding that ascites
were negative for endotoxins.

Case Report
A 58-year-old Japanese male with end-stage renal failure due to chronic glomerulonephritis andreceiving chronic hemodialysis since 1980 underwent kidney transplantation from an unrelateddonor in October 1998. This case was also complicated by chronic hepatitis C.
In January 2004, liver cirrhosis with a Child-Pugh score of 6 points (grade A) was diagnosed based
on total serum bilirubin (T-bil) of 0.7 mg/dl, serum albumin (S-alb) of 2.8 g/dl, prothrombin timeinternational normalized ratio (PT-INR) of 1.1, and medical control of ascites. During follow-up,
serum creatinine (S-Cr) was 0.8 mg/dl. Immunosuppressive therapy consisted of mycophenolate
mofetil (500 mg/day), tacrolimus hydrate (2 mg/day), and prednisolone (7.5 mg/day). In November
2004, 160 mg/day furosemide and 4 mg/day thiazide were administered for increased ascites, but theeffect was insufficient.
On December 26, 2004, the patient was hospitalized for fever, abdominal pain, dyspnea, andcopious ascites. On admission, patient height was 167.6 cm, body weight 59.2 kg, body temperature
39.2°C, blood pressure 154/92 mm Hg, and pulse 72 beats/min. Physical examination found jaundicein the bulbar conjunctivae. The abdomen was diffusely tender with rigidity and rebound. There wasno sign of hepatic encephalopathy. Medical history was unremarkable apart from
immunosuppressants and diuretics. Table 1 presents the laboratory findings on admission, including
a white blood cell count of 8,500/μl and a C-reactive protein (CRP) level of 11.3 mg/dl. Based on T-bil
2.6 mg/dl, S-alb 2.7 g/dl, PT-INR 1.1, and the presence of refractory ascites, liver cirrhosis with aChild-Pugh score of 9 points (grade B) was diagnosed. The ascites were exudative and demonstrated a
specific gravity of 1.032, total protein of 3.1 g/dl, total albumin of 1.6 g/dl, Rivalta’s reaction positive,
and polymorphonuclear leukocyte (PMN) count of 940 cells/mm 3. Renal failure was identified based139

Case Rep Nephrol Urol 2012;2:138–144
DOI: 10.1159/000343247

Published online:© 2012 S. Karger AG, Basel
September 24, 2012 ISSN 1664–5510
www.karger.com/cru

on a blood urea nitrogen (BUN) level of 55 mg/dl and S-Cr of 2.3 mg/dl. Tacrolimus troughconcentration was not problematic, at 6.2 ng/ml; urinalysis was also normal; fractional excretion of
urea nitrogen (FeUN) was low, at 20%; and on this basis, prerenal failure was diagnosed.
Abdominal computed tomography scan and abdominal ultrasound showed copious ascites, butthere was no evidence of abscess, perforation, or penetration. Diagnosis of SBP was thus based on theclinical and laboratory findings. Several blood and ascites cultures did not demonstrate pathogenicorganisms.
Fig. 1 presents the clinical course and treatment pursued. Immediately after ascites puncture, webegan empirical antibiotic therapy with ceftriaxone intravenously (1 g/day), and mycophenolate
mofetil and tacrolimus hydrate were discontinued. Two days after initiation of treatment, bodytemperature was normal, and abdominal pain had ceased, but the copious ascites were not improved.
Abdominal paracentesis (3 l/day) and albumin transfusion (25%, 100 ml/day) were performed 6times, but the effect was temporary, and control of ascites was poor. S-alb decreased to 1.8 g/dl, renal
failure deteriorated, urinary volume declined, and ascites increased yet further. Due to normal
urinalysis and low FeUN of 20%, aggravation of prerenal failure was a suspected factor.
Because the PMN count in ascites decreased to 58 cells/mm 3 and ascites were also endotoxin
negative (0.8 pg/ml), CART was initiated, with 3.0 l of ascites filtrated and concentrated to 0.3 l in 120
min. The concentrated fluid was drip-infused back into the patient at the rate of 0.15 l/h. The
apparatus used was the Plascit 01 and the columns used were model AHF-MOW for the ascites
filtration and the model AHF-UNH for the ascites concentration, all manufactured by Asahi Kasei
Medical (Tokyo, Japan).
At such time, S-alb rose gradually, and the level of ascites decreased. CART was performed a totalof 6 times, and ascites were well controlled, with no observation of fever, hypotension, or otheradverse effects. Biochemical results also improved to T-bil 0.7 mg/dl, S-alb 3.2 g/dl, BUN 37 mg/dl, SCr 1.2 mg/dl, and CRP 0.0 mg/dl. No findings suggesting rejection of a transplanted kidney wereobserved, mycophenolate mofetil (500 mg/day) and tacrolimus hydrate (2 mg/day) were reinitiated,
and the patient was discharged.

Discussion
Peritonitis in immunosuppressed renal transplant recipients remains associatedwith high morbidity and mortality [1]. The diagnostic criteria for SBP are bacterial
growth from the ascitic fluid plus an ascitic PMN count of more than 250/μl, or ascitic
fluid with a PMN count of more than 500/μl, even in the absence of a positive culture[2]. In this case, SBP was diagnosed on the basis of an ascitic PMN count of 940
cells/mm3 and the absence of an obvious intra-abdominal source of infection.
SBP is thought to result from a combination of factors inherent in cirrhosis andascites, such as prolonged bacteremia secondary to compromised host defense,
intrahepatic shunting of colonized blood, and defective bactericidal activity within the
ascitic fluid [3]. Some 40% to 50% of all patients with SBP have negative cultures ofboth blood and ascitic fluid, as in this case [4, 5].
Since the 1985 seminal study, which showed better outcomes with cefotaxime thanwith the combination of ampicillin and tobramycin, third-generation cephalosporins
have been the agents of choice in the management of SBP. Subsequently, several studies
have reinforced the role of third-generation cephalosporins in an effort to determine
the optimal dose and duration of therapy [5–9].
Guidelines for SBP have been published by The International Ascites Club andsuggest several antibiotics that may be used for empirical treatment, including140

Case Rep Nephrol Urol 2012;2:138–144
DOI: 10.1159/000343247

Published online:© 2012 S. Karger AG, Basel
September 24, 2012 ISSN 1664–5510
www.karger.com/cru

cefotaxime, cefonicid, ceftizoxime, ceftriaxone, ceftazidime, and amoxicillin-clavulanic
acid [10]. Based on the reports cited, we selected ceftriaxone, and given the prerenal
failure status, dosage was reduced to 1 g/day. This treatment achieved a goodtherapeutic effect.
Acute renal failure develops in 33% of patients with SBP and is a major cause ofdeath [11]. After abdominal paracentesis, intravenous infusion of albumin has beenused to avoid reduction of the effective volume and prerenal failure [12, 13]. A
randomized, controlled study of patients with SBP showed that patients receiving
cefotaxime with a high-volume albumin transfusion (1.0–1.5 g/kg) were significantly
less likely to have irreversible renal failure and had lower mortality [14]. Japan,
however, relies on imports for 70% of its albumin formulations, which complicateshigh-volume albumin transfusion (e.g., 1.0–1.5 g/kg).
CART is a treatment which maintains albumin and globulin by filtration,
concentration, and reinfusion of drained ascites. A single CART treatment reportedly
can reinfuse approximately 60 g of albumin, and this amount corresponds to a highvolume albumin transfusion capable of reducing the associated risk of infection orallergic reaction [15]. However, CART is more expensive than the high volume ofalbumin transfusion (60 g) in Japan (90,000 vs. 60,000 yen).
CART cannot eliminate endotoxins, which present a danger to SBP patients as a riskof endotoxin shock or temporary fever. SBP is deemed resolved when all signs ofinfection have disappeared and the ascitic fluid PMN count is below 250 cells/mm3 [4].
In our case, CART was pursued after the PMN count in ascites decreased to 58
cells/mm3 and the ascites were found to be endotoxin negative. At such time, no shockor temporary fever was observed. Though administration of prednisolone (7.5 mg/day)as immunosuppressive therapy may have prevented occurrence of a temporary fever,
we believe that CART is a safe treatment even for endotoxin-negative SBP patients.

Disclosure Statement
There are no financial disclosures.

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Case Rep Nephrol Urol 2012;2:138–144
DOI: 10.1159/000343247

Published online:© 2012 S. Karger AG, Basel
September 24, 2012 ISSN 1664–5510
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Table 1. Laboratory findings on admission
Urinalysis
Protein
GlucoseOccult blood
Bilirubin––––

Blood cell countWhite blood cells, /μl
Hematocrit, %Hemoglobin, g/dl
Red blood cells, ×104/μl
Platelets, ×104/μl

8,500
31.9
10.8
337
9.2

Coagulation test
PT-INR
Activated partial thromboplastin time, s

1.10
38.5

Blood chemistry
Total protein, g/dl
Alb, g/dl
Aspartate aminotransferase, U/lAlanine aminotransferase, U/l
Lactate dehydrogenase, U/l
Alkaline phosphatase, U/lγ-Glutamyl transpeptidase, U/l
Cholinesterase, U/lT-bil, mg/dl
BUN, mg/dl
Cr, mg/dl
Na, mEq/l
K, mEq/l
Cl, mEq/l
CRP, mg/dl

5.3
2.7
53
32
521
488
478
113
2.6
55
2.3
134
4.0
100
11.3

Serological study
Hepatitis B virus antigen
Hepatitis C virus antibody–+

Ascitic fluid analysis
Color
Turbidity
Leukocytes, cells/mm3
Specific gravity
Total protein, g/dl
Alb, g/dl
Bacterial culture
Rivalta’s reaction

yellow
cloudy
940
1.032
3.1
1.6
negative
positive

Othersα-Fetoprotein, ng/ml
Child-Pugh score, points
Tacrolimus trough concentration, ng/ml

2.0
9
6.2

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Case Rep Nephrol Urol 2012;2:138–144
DOI: 10.1159/000343247

Published online:© 2012 S. Karger AG, Basel
September 24, 2012 ISSN 1664–5510
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Fig. 1. Clinical course. We began empirical antibiotic therapy with ceftriaxone intravenously(1 g/day). Abdominal paracentesis (3 l/day) and albumin transfusion (25%, 100 ml/day) were
performed 6 times, but the effect was temporary, and control of ascites was poor. S-alb decreased to
1.8 g/dl, prerenal failure deteriorated, urinary volume declined, and ascites increased yet further.
Because the PMN count in ascites decreased to 58 cells/mm 3 and ascites were also endotoxin
negative, CART was initiated, with 3.0 l of ascites filtrated and concentrated to 0.3 l in 120 min. At
such time, S-alb rose gradually, and the level of ascites decreased. CART was performed a total of 6
times, and ascites were well controlled, with no observation of fever, hypotension, or other adverse
effects. Biochemical results also improved to S-alb 3.2 g/dl and S-Cr 1.2 mg/dl, and the patient wasdischarged.

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