Annals of Clinical & Laboratory Science 36:96-100 (2006)
© 2006 Association of Clinical Scientists
Hepatorenal Syndrome: Resolution of Ascites by Continuous Renal Replacement Therapy in an Alcoholic Coinfected with Hepatitis B, C, and Human Immunodeficiency Viruses
Paul C. Hansard1,
Ricardo A. Manning1,
M.A. Haseeb1,2,3 and
Martin J. Salwen3
1 Departments of Medicine, 2 Microbiology & Immunology, and 3 Pathology, Downstate Medical Center, State University of New York, and Kings County Hospital Center, Brooklyn, New York
Address correspondence to Paul C. Hansard, M.D., Kings County Hospital Center, 451 Clarkson Ave., Brooklyn, NY 11203, USA; tel 718 245 3820; fax 718 245 3764; e-mail phansard{at}pol.net.
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Abstract
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A 39-yr-old male with hepatorenal syndrome type 1 and refractory ascites was treated with continuous renal replacement therapy (CRRT) resulting in clinical improvement. He was positive for antibodies to hepatitis B, C, and human immunodeficiency viruses, and had a history of chronic alcohol and iv drug abuse. The patient had 4 hospital admissions during a 12-wk period. He first presented with advanced liver disease including pedal edema and a serum ammonia level of 56 µmol/L (reference range: 11 – 35 µmol/L). In subsequent admissions, he had asterixis, nausea, vomiting, jaundice, and worsening pedal edema. On his 4th admission, there was lethargy, tense ascites, decreased urinary output, bilateral edema of the lower extremities and scrotum, serum creatinine of 6.2 mg/dl (reference range: 0.6 – 1.5 mg/dl), and weight gain of 16 kg during the prior 8 wk. During the first 3 hospitalizations, he was treated with lactulose with slight improvement. On the 4th admission, he was started on low-dose dopamine (3 µg/kg/min) and 25% salt-poor albumin without clinical improvement. A pulmonary artery catheter was placed and hemofiltration by CRRT was performed for 5 days, with removal of 26.7 L of fluid and a net reduction of 11 kg of body weight. Serum creatinine decreased to 4.2 mg/dl during CRRT and was 2.2 mg/dl at hospital discharge 2 weeks later. His PaO2 improved from 66 to 78 mmHg and his systemic vascular resistance increased from 571 to 799 dyne·sec/cm5. CRRT was effective in relieving severe fluid retention and producing marked clinical improvement. We suggest that CRRT should be considered for the treatment of refractory ascites including that caused by hepatorenal syndrome.
Keywords: continuous renal replacement therapy, hemofiltration, hepatorenal syndrome, ascites
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Introduction
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Hepatorenal syndrome (HRS) has long been known to occur in individuals with advanced liver disease [1]. Its pathophysiologic mechanisms are poorly understood. Renal dysfunction or failure occurs in patients with severe liver disease, but the kidneys demonstrate no intrinsic pathologic alteration. Renal dysfunction results from decreased renal perfusion, due in part to splanchnic arterial vasodilation caused by portal hypertension and increased nitric oxide synthesis [2]. The complexity of HRS is evident from the diagnostic criteria of the International Ascites Club that are based on the assessment of multiple measures of liver and kidney functions [2–4]. Management approaches for overt HRS, specifically type 1, short of liver transplantation, have not resulted in marked clinical improvement or increased survival. Mortality in cases of rapidly progressive HRS type 1 approaches 100% within 10 wk after onset [5].
We report successful treatment of a patient with HRS type 1. Clinical improvement of refractory ascites was accomplished by hemofiltration with continuous renal replacement therapy (CRRT). Biochemical and physiological data are presented to document the patient’s substantial improvement following completion of CRRT.
The CRRT procedure, as either continuous veno-venous hemofiltration (CVVH) or continuous arterio-venous hemofiltration (CAVH), is used to remove excess fluid. Blood is circulated through a hemofilter, yielding an ultrafiltrate with the composition of plasma water, containing low molecular weight non-protein-bound solutes. The cellular components and high molecular weight substances in the blood are returned to the patient [6,7].
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Case Report
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The patient was a 39-yr-old male who was infected with hepatitis B, C, and human immunodeficiency viruses. He had a history of chronic alcohol and iv drug abuse, but was negative for HIV-associated opportunistic infections.
First admission.
The patient presented with lethargy, worsening resting tremors, and altered mental status. During 2 days before admission, he had several episodes of vomiting following meals. He was receiving therapy with zidovudine (AZT), lamivudine (3TC), indinavir, methadone, and thiamine. Physical examination findings were ecchymoses of the lower extremities and pedal edema, limiting mobility. Laboratory data on admission (Table 1
) included an elevated serum ammonia level of 56 µmol/L (reference range: 11 – 35 µmol/L). Computer tomography (CT) of the head with contrast showed no abnormalities; Gram stain and culture of cerebrospinal fluid (CSF) were negative. Anti-retroviral medications were temporarily discontinued and the patient was given lactulose. There was gradual resolution of the lethargy and resting tremors. The patient left the hospital against medical advice on the third day.
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Table 1. Laboratory data for serum or plasma samples and hemodynamic values of the patient for each of the 4 consecutive hospitalizations. Data for the first 3 admissions represent those recorded at admission. The fourth admission data represent those recorded before, during, and after initiation of CRRT. See text for abbreviations. Reference ranges are in parentheses.
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Second admission.
Approximately 2 wk later, the patient was readmitted due to hepatic encephalopathy with asterixis, nausea, and vomiting. Physical findings were similar to those of the prior admission except that pedal edema was absent. An abdominal sonogram showed hepatosplenomegaly with homogenous architecture. Blood and CSF cultures for bacteria and fungi were negative. The patient again improved in response to lactulose and was discharged after 2 days.
Third admission.
Four weeks later, the patient presented with bipedal edema, jaundice, and passage of bright red blood per rectum. Laboratory data were similar to those of prior admissions (Table 1
). He was treated with lactulose, vitamin K, and was transfused with 4 units each of packed red blood cells and fresh frozen plasma.
Fourth Admission.
Eight wk after first hospital admission and 18 days after his last discharge, the patient presented with a 10-day history of lethargy, progressive abdominal distention and tenderness, and decreased urinary output. He stated that for a week he had been too weak to walk and that he had been anuric for the prior 24 hr. He denied recent alcohol consumption and his toxicology screen test identified only methadone, which was a prescribed medication. He weighed 77 kg (baseline weight: 61 kg). Physical examination was significant for icterus, pallor, and spider nevi. There were bilateral pulmonary crepitations, bronchial breathing with egophony, and increased tactile fremitus. His abdomen was protuberant, consistent with ascites, but neither hepatomegaly nor splenomegaly was evident on palpation. He had testicular atrophy and bilateral lower extremity edema extending to the level of the thigh and inclusive of the scrotum.
Bilateral pleural effusions and interstitial infiltrates consistent with pulmonary edema were seen on chest X-ray. Abdominal X-ray showed no free air or obstruction. Diagnostic thoracentesis (RBC, 4050/mm3; WBC, 6/mm3; glucose, 114 mg/dl; LDH, 39 U/L; protein, 1.0 g/dl; pH 7.45) and paracentesis (RBC, 2090/mm3; WBC, 30/mm3; glucose, 84 mg/dl; protein, 0.5 g/dl) were performed and both fluids were determined to be transudates. His serum creatinine level was 6.2 mg/dl (reference range: 0.6 – 1.5 mg/dl). He was anemic and had prolonged plasma prothrombin time (PT) and partial thromboplastin time (PTT) (Table 1). Urine osmolality was 324 mOsm/kg; urine electrolytes were: Na, <10 mmol/L; K, 37.2 mmol/L; and Cl, 15 mmol/L. Bacterial and fungal cultures of pleural fluid, ascitic fluid, blood, and urine were negative.
Based on these findings and his co-morbidities, the diagnoses of pre-renal azotemia or hepatorenal syndrome were considered. The therapeutic goal was to improve renal perfusion through hydration with non-invasive monitoring of vital signs. The patient was advised of the severity of his condition and his ominous prognosis without intervention. He was advised of the risks and potential complications as well as possible benefits of CRRT and invasive monitoring. The patient’s written consent for CRRT was obtained and he was transferred to the medical intensive care unit (MICU).
A pulmonary artery catheter was placed via a median basilic approach to monitor hemodynamic response to therapy. The patient was started on low-dose dopamine (3 µg/kg/min) and salt-poor albumin (25% albumin/50 ml). His urinary output increased without change in serum creatinine and he had weight reduction of only 0.6 kg during 7 days. It was determined that drug therapy alone was ineffective in achieving the desired volume reduction. A double-lumen femoral vein catheter was placed and low-volume CRRT was begun using CVVH with a blood flow of 125 ml/min, removing 300 – 400 ml of ultrafiltrate/hr. A Minntech RenaFlo II (HF-400) hemofilter (Minntech, Mineapolis, MN) was primed (using 1 L of 0.9% NaCl containing 5000 units of sodium heparin) until the air was replaced with the solution. Routine anticoagulation of the hemofilter was accomplished by heparinization with 25,000 units of sodium heparin in 250 ml of 0.9% NaCl administered at approximately 400 units heparin/hr [6,7]. CRRT was continued for 5 days with the removal of a total of 26.7 L of ultrafiltrate. There was concurrent hemodynamic and biochemical improvement (Table 1, Fig. 1), as well as improved oxygenation with decreased ventilation (Fig. 2). Serum creatinine decreased to 4.2 mg/dl during CRRT and was 2.2 mg/dl at hospital discharge 2 wk later. PaO2 improved from 66 to 78 mmHg and systemic vascular resistance increased from 571 to 799 dyne·sec/cm5.
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Fig. 1. Patient’s daily net fluid balance (NFB) during days in the medical ICU. Arrow = start of CRRT. NFB = total intake (oral + iv fluids) – total output (urine + ultrafiltrate).
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Fig. 2. Patient’s pCO2 and PaO2 levels. Arrow = start of CRRT. Bars represent pCO2 and the line represents PaO2.
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The patient was discharged from the MICU on the 15th day of hospitalization and from the hospital on the 26th day. There had been a net weight-loss of 11 kg and the patient’s body weight was 61 kg on discharge (Fig. 3).
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Fig. 3. Patient’s body wt and serum creatinine levels (mg/dl) before and after sart of CRRT (indicated by arrow). Bars represent body wt and the line represents creatinine levels.
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Discussion
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Management and treatment of HRS with or without ascites has been a challenge to medical practitioners ever since its description [2,5]. In HRS with anasarca the prognosis is guarded and most diuretic-refractory patients succumb. Treatment modalities have been limited to the use of diuretics, large volume paracentesis, and portosystemic shunting, all with poor outcomes. The only effective treatment resulting in renal recovery for this condition is liver transplantation. Although restoration of renal function appears to be the key to reversing the HRS, conventional hemodialysis, its various modifications, and even kidney transplantation have not resulted in survival beyond a few days [2–5].
Our patient met the International Ascites Club’s Diagnostic Criteria of HRS type I [2,4]. He had a low systemic vascular resistance (SVR) and a high cardiac index (CI), consistent with an underlying infection, portal hypertension, orvasodilation. All cultures were negative and no pharmacologic agent had been administered. There was no evidence of GI hemorrhage on the 4th admission, nor was the patient on diuretic therapy. Infusion of low-dose dopamine (3 µg/Kg/min) and albumin (25%) resulted in an increase in SVR (571 to 745 dyne·sec/cm5) and a decrease in CI (5.6 to 4.6 L/min/m2). There were improvements in SVR and CI, but there was no significant change in net fluid balance and CRRT was therefore initiated. CRRT resulted in reduction of the ascites and pulmonary interstitial edema, while the patient remained hemodynamically stable (Table 1); the serum creatinine level decreased and net fluid balance improved (Fig. 1).
Since ultrafiltration is known to remove low molecular weight molecules from blood, the reduction in serum creatinine was expected. However, the continued creatinine reduction after CRRT had been stopped was surprising and suggests that other molecules contributing to the pathogenesis of HRS may have been removed. Antidiuretic hormone, norepinephrine, nitric oxide, and neuropepitde Y have all been implicated as possible potentiators of fluid retention and have molecular sizes that would permit their removal by CRRT. There is no known circulating toxin associated with HRS. The temporal relationship between circulating levels of these substances and the clinical condition of such patients warrants investigation.
In our patient, CRRT resulted in resolution of ascites and edema, and improvement of renal function and hemodynamics. Despite significant coagulopathy, the CRRT procedure was performed safely and without incident. CRRT successfully achieved clinical improvement in this patient and should be considered in the therapy for refractory ascites including that resulting from HRS.
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References
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- Hecker R, Sherlock S. Electrolyte and circulatory changes in terminal liver failure. Lancet 1956;268:1121–1125.
- Arroyo V, Guevara M, Ginès P. Hepatorenal syndrome in cirrhosis: pathogenesis and treatment. Gastroenterology 2002;122:1658–1676.[Medline]
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- Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, Reynolds TB, Ring-Larsen H, Scholmerich J. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology 1996;23:164–176.[Medline]
- Wong F, Blendis L. New challenge of hepatorenal syndrome: prevention and treatment. Hepatology 2001;34:1242–1251.
- Hansard PC, HaseebMA. Continuous renal replacement therapy: an underutilized resource. Pulmonary Perspectives 2001;18:4–6.
- Hansard PC, Haseeb MA, Manning RA, Salwen MJ. Recovery of bacteria by continuous renal replacement therapy in septic shock and by ultrafiltration from an in vitro model of bacteremia. Crit Care Med 2004;32:932–937.[Medline]
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Abstract
Introduction
