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Lang M, Lang AL, Tsui BQ, Wang W, Erly BK, Shen B, Kapoor B. Renal-function change after transjugular intra-hepatic portosystemic shunt placement and its relationship with survival: a single-center experience. Gastroenterol Rep (Oxf) 2021; 9:306-312. [PMID: 34567562 PMCID: PMC8460113 DOI: 10.1093/gastro/goaa081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 09/15/2020] [Accepted: 09/27/2020] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND The effect of transjugular intra-hepatic portosystemic shunt (TIPS) placement on renal function and the correlation of post-TIPS Cr with mortality remain unclear. This study aimed to assess the effect of TIPS placement on renal function and to examine the relationship between post-TIPS Cr and mortality risk. METHODS A total of 593 patients who underwent de novo TIPS placement between 2004 and 2017 at a single institution were included in the study. The pre-TIPS Cr level (T0; within 7 days before TIPS placement) and post-TIPS Cr levels, at 1-2 days (T1), 5-12 days (T2), and 15-40 days (T3), were collected. Predictors of Cr change after TIPS placement and the 1-year mortality rate were analysed using multivariable linear-regression and Cox proportional-hazards models, respectively. RESULTS Overall, 21.4% of patients (n = 127) had elevated baseline Cr (≥1.5 mg/dL; mean, 2.51 ± 1.49 mg/dL) and 78.6% (n = 466) had normal baseline Cr (<1.5 mg/dL; mean, 0.92 ± 0.26 mg/dL). Patients with elevated pre-TIPS Cr demonstrated a decrease in post-TIPS Cr (difference, -0.60 mg/dL), whereas patients with normal baseline Cr exhibited no change (difference, <0.01 mg/dL). The 30-day, 90-day, and 1-year mortality rates were 13%, 20%, and 32%, respectively. Variceal bleeding as a TIPS-placement indication (hazard ratio = 1.731; P = 0.036), higher T0 Cr (hazard ratio = 1.834; P = 0.012), and higher T3 Cr (hazard ratio = 3.524; P < 0.001) were associated with higher 1-year mortality risk. CONCLUSION TIPS placement improved renal function in patients with baseline renal dysfunction and the post-TIPS Cr level was a strong predictor of 1-year mortality risk.
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Affiliation(s)
- Min Lang
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Angela L. Lang
- Department of Anesthesia, Critical Care, and Pain Management, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Brian Q. Tsui
- Department of Radiology, UCLA Medical Center, Los Angeles, CA, USA
| | - Weiping Wang
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Brian K. Erly
- Colorado School of Public Health, Aurora, Colorado, USA
| | - Bo Shen
- The Inflammatory Bowel Disease Center at Columbia, Columbia University Irving Medical Center, New York, NY, USA
| | - Baljendra Kapoor
- Division of Vascular and Interventional Radiology, Imaging Institute, Cleveland Clinic, Cleveland, OH, USA
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Fida S, Khurshid SMS, Mansoor H. Frequency of Hepatorenal Syndrome Among Patients With Cirrhosis and Outcome After Treatment. Cureus 2020; 12:e10016. [PMID: 32983712 PMCID: PMC7515548 DOI: 10.7759/cureus.10016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Introduction Hepatorenal syndrome is the third most common cause of admissions among patients with liver cirrhosis and has a high mortality rate. It is a progressive deterioration of renal function in a patient with acute or chronic liver failure. The only definite curative treatment of choice for hepatorenal syndrome is liver transplantation. This study aimed to determine the frequency of hepatorenal syndrome among patients with liver cirrhosis and to determine its outcome after treatment. Patients and Methods This case series prospective study was conducted at the Department of Medicine, CMH Lahore Medical College and Institute of Dentistry, Pakistan, from January 2019 to December 2019. The study included 136 patients of cirrhosis who were identified and worked up for hepatorenal syndrome. The patients with liver cirrhosis diagnosed as having hepatorenal syndrome were given treatment comprising injection terlipressin 2 mg four times a day and injection Haemaccel twice a day for two weeks, and after that the outcome was measured with a follow-up of six weeks. Results A total of 136 patients of cirrhosis were included in the study. Of the patients, 14 (10.3%) were diagnosed as suffering from hepatorenal syndrome. These diagnosed cases were given treatment for two weeks. Three (21.4%) of the patients having hepatorenal syndrome did not show any response, two (14.3%) patients recovered partially, four (28.6%) patients recovered fully, and four (28.6%) expired within one month of the treatment. One (7.14%) patient was referred during the treatment for liver transplant. Conclusions Hepatorenal syndrome is a common complication of cirrhosis. The treatment of systemic vasoconstrictors for hepatorenal syndrome proved to be effective in our study and should be the first priority for treating hepatorenal syndrome especially in places like Pakistan where liver transplantation is not that easily available.
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Affiliation(s)
- Samina Fida
- Medicine, CMH Lahore Medical College and Institute of Dentistry, Lahore, PAK
| | | | - Hala Mansoor
- Gastroenterology and Hepatology, CMH Lahore Medical College and Institute of Dentistry, Lahore, PAK
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Yeboah MM, Hye Khan MA, Chesnik MA, Skibba M, Kolb LL, Imig JD. Role of the cytochrome P-450/ epoxyeicosatrienoic acids pathway in the pathogenesis of renal dysfunction in cirrhosis. Nephrol Dial Transplant 2019; 33:1333-1343. [PMID: 29361048 DOI: 10.1093/ndt/gfx354] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 11/24/2017] [Indexed: 02/06/2023] Open
Abstract
Background Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver cirrhosis that is characterized by hemodynamic alterations in the kidney and other vascular beds. Cytochrome P(CYP)-450 enzymes metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acids. These eicosanoids regulate blood pressure, vascular tone and renal tubular sodium transport under both physiological and pathophysiological states. Methods Experiments were performed to investigate the role of the CYP system in the pathogenesis of renal dysfunction during cirrhosis. Rats underwent bile duct ligation (BDL) or sham surgery and were studied at 2, 4 and 5 weeks post-surgery. In additional experiments, post-BDL rats were treated with three daily intraperitoneal doses of either the selective epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH) or a vehicle, starting on Day 22 after surgery. Results BDL led to progressive renal dysfunction that was associated with reduced renal cortical perfusion but without any overt histologic changes, consistent with HRS. CYP isoform enzyme expression was significantly altered in BDL rats. In the kidney, CYP2C23 expression was upregulated at both the mRNA and protein levels in BDL rats, while CYP2C11 was downregulated. Histologically, the changes in CYP2C23 and CYP2C11 expression were localized to the renal tubules. EET production was increased in the kidneys of BDL rats as assessed by urinary eicosanoid levels. Finally, treatment with the selective epoxygenase inhibitor MSPPOH significantly reduced renal function and renal cortical perfusion in BDL rats, suggesting a homeostatic role for epoxygenase-derived eicosanoids. Conclusions The CYP/EET pathway might represent a novel therapeutic target for modulating renal dysfunction in advanced cirrhosis.
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Affiliation(s)
- Michael M Yeboah
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Md Abdul Hye Khan
- Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Marla A Chesnik
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Melissa Skibba
- Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Lauren L Kolb
- Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - John D Imig
- Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA
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Effect of different therapeutic modalities on systemic, renal, and hepatic hemodynamics and short-term outcomes in cirrhotic patients with spontaneous bacterial peritonitis. Eur J Gastroenterol Hepatol 2016; 28:777-85. [PMID: 27097354 DOI: 10.1097/meg.0000000000000635] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a major risk factor for hepatorenal syndrome. Albumin infusion has been shown to prevent renal impairment and reduce mortality in SBP. The study aimed to compare the effect of different therapeutic modalities on hemodynamics and short clinical outcomes in high-risk patients with SBP. METHODS Two hundred cirrhotic patients with SBP and bilirubin greater than 4 mg[Fraction Slash]dl or creatinine more than 1 mg[Fraction Slash]dl were enrolled. Patients were randomized to receive albumin, terlipressin, low-dose albumin plus terlipressin, or midodrine. Systemic, renal, and hepatic hemodynamics were estimated at baseline, 3, and 10 days of treatment. Renal impairment was diagnosed when the blood urea nitrogen or serum creatinine levels increased by more than 50% of the pretreatment value. RESULTS SBP resolved in most of patients in all groups (P>0.05). Cardiac output and portal flow decreased, whereas systemic vascular resistance increased significantly in terlipressin and albumin plus terlipressin groups compared with the albumin group after 3 and 10 days. After 10 days, plasma renin activity, renal, and hepatic arteries resistive index were significantly higher in the midodrine group compared with the albumin group. The midodrine group did not show any significant changes in the heart rate, mean arterial pressure, cardiac output, and portal blood flow compared with the albumin group after 3 or 10 days. There was no significant difference in renal impairment or mortality between any of the groups. CONCLUSION Terlipressin and low-dose albumin plus terlipressin could be used as a therapeutic alternative to standard-dose albumin in high-risk SBP patients.
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Silveira KCSD, Viau CM, Colares JR, Saffi J, Marroni NP, Porawski M. Cirrhosis induces apoptosis in renal tissue through intracellular oxidative stress. ARQUIVOS DE GASTROENTEROLOGIA 2015; 52:65-71. [PMID: 26017086 DOI: 10.1590/s0004-28032015000100014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Accepted: 10/07/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. OBJECTIVES We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. METHODS Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. RESULTS In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. CONCLUSIONS These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.
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Affiliation(s)
| | | | - Josiane Raskopf Colares
- Laboratório de Estresse Oxidativo, Universidade Luterana do Brasil - ULBRA, Canoas, RS, Brasil
| | - Jenifer Saffi
- Laboratório de Genética Toxicológica, UFCSPA, Porto Alegre, RS, Brasil
| | - Norma Possa Marroni
- Laboratório de Estresse Oxidativo, Universidade Luterana do Brasil - ULBRA, Canoas, RS, Brasil
| | - Marilene Porawski
- Laboratório de Fisiologia, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, RS, Brasil
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Sampaio MS, Martin P, Bunnapradist S. Renal dysfunction in end-stage liver disease and post-liver transplant. Clin Liver Dis 2014; 18:543-60. [PMID: 25017075 DOI: 10.1016/j.cld.2014.05.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Renal dysfunction is a frequent complication in patients with end-stage liver disease awaiting orthotopic liver transplantation and in the post-liver transplant period. Although the stereotypical form of renal dysfunction is the hepatorenal syndrome, other causes of acute kidney injury in this population include prerenal azotemia and acute tubular necrosis. Renal injury in a patient with cirrhosis is associated with a poor prognosis.
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Affiliation(s)
- Marcelo S Sampaio
- Division of Nephrology, Department of Medicine, Kidney and Pancreas Transplant Program, David Geffen School of Medicine at UCLA, 1015 Gayley Avenue, Suite 220, Los Angeles, CA 90024, USA
| | - Paul Martin
- Division of Hepatology, Miller School of Medicine, University of Miami, 1500 NW 12 Avenue, Jackson Medical Tower E-1101, Miami, FL 33136, USA
| | - Suphamai Bunnapradist
- Division of Nephrology, Department of Medicine, Kidney and Pancreas Transplant Program, David Geffen School of Medicine at UCLA, 1015 Gayley Avenue, Suite 220, Los Angeles, CA 90024, USA.
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Lau C, Martin P, Bunnapradist S. Management of renal dysfunction in patients receiving a liver transplant. Clin Liver Dis 2011; 15:807-20. [PMID: 22032530 DOI: 10.1016/j.cld.2011.08.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Renal dysfunction is a frequent complication in patients with endstage liver disease awaiting orthotopic liver transplantation. Although the stereotypical form of renal dysfunction is the hepatorenal syndrome, common causes of acute kidney injury include prerenal azotemia and acute tubular necrosis in this population. Management involves hemodynamic support, renal replacement therapy, and mitigation of risk factors. Renal dysfunction in a cirrhotic patient usually implies a poor prognosis in the absence of liver transplantation. An important issue is the frequent need for kidney, in addition to liver, transplantation if renal insufficiency has been persistent in a decompensated cirrhotic.
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Affiliation(s)
- Christine Lau
- Kidney and Pancreas Transplant Program, Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
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Lee KS, Muñoz A, Báez AB, Ngo L, Rofsky NM, Pedrosa I. Corticomedullary differentiation on T1-Weighted MRI: comparison between cirrhotic and noncirrhotic patients. J Magn Reson Imaging 2011; 35:644-9. [PMID: 22031466 DOI: 10.1002/jmri.22852] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2011] [Accepted: 09/23/2011] [Indexed: 01/15/2023] Open
Abstract
PURPOSE To determine whether corticomedullary differentiation (CMD) is increased in patients with cirrhosis compared to controls on axial T1-weighted magnetic resonance imaging (MRI). MATERIALS AND METHODS Sixty patients with cirrhosis and 60 age-matched controls without renal disease underwent axial, T1-weighted in-phase gradient echo abdominal MRI. Each group of 60 was subdivided into three groups of 20 patients based on age: 18 to 45 years old; 45 to 65 years old; and greater than 65 years old. Signal intensity measurements of regions of interest obtained within the cortex and medulla of each kidney were recorded and the cortex-to-medulla contrast-to-noise ratio (CM-CNR) was calculated. Each patient's estimated glomerular filtration rate (eGFR) was recorded. RESULTS Mean CM-CNR for both kidneys in cirrhotic patients (19.1 ± 10.5) was significantly higher than in controls (12.4 ± 5.0) (P < 0.0001). No significant correlation was observed between CM-CNR and eGFR levels for both cirrhotics and controls (P > 0.05). When stratified by age groups, no difference was observed in the mean CM-CNR for both kidneys among these three subgroups for both cirrhotics and controls (P > 0.05). CONCLUSION Cirrhotic patients with normal renal function have an increased CMD compared to age-matched controls.
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Affiliation(s)
- Karen S Lee
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
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Rademacher S, Oppert M, Jörres A. Artificial extracorporeal liver support therapy in patients with severe liver failure. Expert Rev Gastroenterol Hepatol 2011; 5:591-9. [PMID: 21910577 DOI: 10.1586/egh.11.59] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Severe liver failure is common and carries a high mortality risk in patients with both acute and acute-on-chronic liver failure. The failing liver constitutes a medical emergency, and in many cases liver transplantation is the only definite treatment. Extracorporeal liver support can be employed as a strategy for bridging to transplantation or recovery. This article focuses on options for artificial (nonbiological) extracorporeal treatment: single-pass albumin dialysis, fractionated plasma separation and adsorption (Prometheus(®)) and the molecular adsorbent recirculatory system. Their different principles, potential advantages and indications are discussed. Despite proven biochemical efficacy, there are little data regarding clinical end points. Thus far, molecular adsorbent recirculatory system therapy in acute and acute-on-chronic liver failure showed no survival benefit compared with standard medical therapy. Prometheus therapy showed reduced mortality in subgroups of higher severity of disease compared with standard medical therapy. Nevertheless, the value of extracorporeal liver support remains to be corroborated by further clinical studies that include the optimal timing, mode, intensity and duration of this treatment.
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Affiliation(s)
- Sibylle Rademacher
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin, 13353 Germany
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10
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Privette TW, Carlisle MC, Palma JK. Emergencies of the Liver, Gallbladder, and Pancreas. Emerg Med Clin North Am 2011; 29:293-317, viii-ix. [DOI: 10.1016/j.emc.2011.01.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Guo SB, Duan ZJ, Li Q, Sun XY. Effect of heme oxygenase-1 on renal function in rats with liver cirrhosis. World J Gastroenterol 2011; 17:322-8. [PMID: 21253390 PMCID: PMC3022291 DOI: 10.3748/wjg.v17.i3.322] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2010] [Revised: 09/25/2010] [Accepted: 10/02/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS).
METHODS: Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group, cobalt protoporphyrin (CoPP) treatment group and sham group. Biliary cirrhosis was established by bile duct ligation in the first three groups. Rats in the ZnPP and CoPP treatment groups received intraperitoneal injection of ZnPP and CoPP, respectively, 24 h before sample collection. Expression of HO-1 mRNA in kidney was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohistochemical analysis. Hematoxylin and eosin staining was performed to observe liver cirrhosis and renal structure. Renal artery blood flow, mean arterial pressure and portal vein pressure, 24 h total urinary volume, serum and urine sodium concentrations, and creatinine clearance rate (Ccr) were also measured.
RESULTS: The HO-1 mRNA and protein expression levels in kidney, 24 h total urinary volume, renal artery blood flow, serum and urine sodium concentration and Ccr were lower in cirrhotic group than in sham group (P < 0.05). However, they were significantly lower in ZnPP treatment group than in cirrhotic group and significantly higher in CoPP treatment group than in cirrhotic group (P < 0.05).
CONCLUSION: Low HO-1 expression level in kidney is an important factor for experimental HRS.
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Narahara Y, Kanazawa H, Taki Y, Kimura Y, Atsukawa M, Katakura T, Kidokoro H, Harimoto H, Fukuda T, Matsushita Y, Nakatsuka K, Sakamoto C. Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis. J Gastroenterol Hepatol 2009; 24:1791-7. [PMID: 19686420 DOI: 10.1111/j.1440-1746.2009.05873.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Terlipressin has been shown to be effective in the management of hepatorenal syndrome. However, how terlipressin exerts its effect on the renal artery is unknown. The aim of the present study was to assess the effects of terlipressin on systemic, hepatic and renal hemodynamics in cirrhosis. METHODS Twenty-eight patients with cirrhosis and portal hypertension were studied. Systemic and hepatic hemodynamics, hepatic and renal arterial resistive indices and neurohumoral factors were measured prior to and 30 min after intravenous administration of 1 mg terlipressin (n = 19) or placebo (n = 9). RESULTS After terlipressin, there were significant increases in both mean arterial pressure (P < 0.001) and systemic vascular resistance (P < 0.001), whereas heart rate (P < 0.001) and cardiac output (P < 0.001) decreased significantly. There was a significant decrease in the hepatic venous pressure gradient (P < 0.001). Portal venous blood flow also decreased significantly (P < 0.001). The mean hepatic arterial velocity increased significantly (P < 0.001). Although there was a significant decrease in the hepatic arterial resistive index (0.72 +/- 0.08 to 0.69 +/- 0.08, P < 0.001) and renal arterial resistive index (0.74 +/- 0.07 to 0.68 +/- 0.07, P < 0.001), portal vascular resistance was unchanged (P = 0.231). Plasma renin activity decreased significantly (P < 0.005), and there was a significant correlation between this decline and the decrease in renal arterial resistive index (r = 0.764, P < 0.005). The effects of terlipressin on systemic, hepatic and renal hemodynamics were observed similarly in patients with and without ascites. Placebo caused no significant effects. CONCLUSION Terlipressin decreases hepatic and renal arterial resistance in patients with cirrhosis.
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Affiliation(s)
- Yoshiyuki Narahara
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Tokyo, Japan.
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Álvarez-Mercado AI, García-Mediavilla MV, Sánchez-Campos S, Abadía F, Sáez-Lara MJ, Cabello-Donayre M, Gil Á, González-Gallego J, Fontana L. Deleterious Effect of Human Umbilical Cord Blood Mononuclear Cell Transplantation on Thioacetamide-Induced Chronic Liver Damage in Rats. Cell Transplant 2009; 18:1069-79. [DOI: 10.3727/096368909x12483162197088] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Our research group investigates whether human mononuclear cells isolated from umbilical cord blood (HUCBM cells) might be valuable in hepatic regenerative medicine. We recently demonstrated that HUCBM cell transplantation improves histological alterations and function of the liver in rats with acute liver damage induced by D-galactosamine. In the present study, HUCBM cells were transplanted into rats with thioacetamide (TAA)-induced liver cirrhosis, an experimental model that generates an intense fibrosis and mimics the histological and biochemical alterations found in the human disease. HUCBM transplantation had no effect on hepatic histology of cirrhotic animals. In contrast, analysis of plasma albumin and total bilirubin, liver damage markers, revealed a harmful effect of HUCBM cell transplantation in our experimental model of liver cirrhosis. Significantly higher plasma urea concentrations, marker of renal function, were observed in the cirrhotic and control rats intraportally injected with HUCBM cells than in those not receiving this therapy. Histological study revealed tubular and glomerular lesions in kidneys of cirrhotic animals transplanted with HUCBM cells. The glomeruli appeared ischemic, and the tubules showed a severe involvement that included peripheral asymmetric vacuolization and disappearance of the tubular lumen. Taken together, the histological and biochemical data suggest that the cirrhotic rats subjected to HUCBM cell therapy developed a hepatorenal syndrome.
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Affiliation(s)
- Ana I. Álvarez-Mercado
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Institute of Nutrition and Food Technology, Biomedical Research Center, Parque Tecnológico Ciencias de la Salud, Granada, Spain
| | - María V. García-Mediavilla
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) and Institute of Biomedicine, University of León, Campus de Vegazana s/n, 24071 León, Spain
| | - Sonia Sánchez-Campos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) and Institute of Biomedicine, University of León, Campus de Vegazana s/n, 24071 León, Spain
| | - Francisco Abadía
- Department of Cell Biology, School of Sciences, University of Granada, Campus de Fuentenueva s/n, 18071 Granada, Spain
| | - María J. Sáez-Lara
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Institute of Nutrition and Food Technology, Biomedical Research Center, Parque Tecnológico Ciencias de la Salud, Granada, Spain
| | - María Cabello-Donayre
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Institute of Nutrition and Food Technology, Biomedical Research Center, Parque Tecnológico Ciencias de la Salud, Granada, Spain
| | - Ángel Gil
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Institute of Nutrition and Food Technology, Biomedical Research Center, Parque Tecnológico Ciencias de la Salud, Granada, Spain
| | - Javier González-Gallego
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) and Institute of Biomedicine, University of León, Campus de Vegazana s/n, 24071 León, Spain
| | - Luis Fontana
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Institute of Nutrition and Food Technology, Biomedical Research Center, Parque Tecnológico Ciencias de la Salud, Granada, Spain
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Midodrine in the prevention of hepatorenal syndrome type 2 recurrence: a case-control study. Dig Liver Dis 2009; 41:298-302. [PMID: 19158001 DOI: 10.1016/j.dld.2008.09.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2008] [Revised: 08/23/2008] [Accepted: 09/09/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatorenal syndrome is a severe complication of cirrhosis. Treatment with terlipressin has currently the best efficacy pedigree, inducing hepatorenal syndrome reversal in a high proportion of patients. However, hepatorenal syndrome recurrence after terlipressin withdrawal is very common, especially in type 2 hepatorenal syndrome. Midodrine, an oral adrenergic vasoconstrictor, has been suggested to be an effective therapy in hepatorenal syndrome. AIMS To analyse the impact of treatment with midodrine after hepatorenal syndrome type 2 reversal induced by terlipressin on the prevention of hepatorenal syndrome recurrence. PATIENTS AND METHODS A case-control design was used. The outcome of 10 patients with hepatorenal syndrome type 2 treated successfully with terlipressin and then with midodrine (7.5-12.5mg/tid) was compared with that of an historical control group of hepatorenal syndrome type 2 patients responders to treatment with terlipressin. Patients and controls were matched by age, plasma renin activity (PRA) levels and severity of renal and liver failure. RESULTS Cases and controls were similar with respect to pre-treatment with terlipressin. The hepatorenal syndrome recurrence probability was the same in the two groups (cases and control: 9/10, 90%, p=ns). No significant differences were found between cases and controls with respect to serum creatinine (1.9+/-0.1mg/dl vs. 2+/-0.2mg/dl), blood creatinine clearance (28+/-5ml/min vs. 24+/-5ml/min), urinary sodium excretion (12+/-6mequiv./d vs. 19+/-4mequiv./d) and PRA levels (17+/-3ng/ml/h) vs. 20+/-3ng/ml/h) after terlipressin withdrawal (p=ns). CONCLUSIONS These results show that in patients responders to terlipressin hepatorenal syndrome recurrence is not different between patients treated with midodrine and subjects who did not receive vasoconstrictor treatment after terlipressin withdrawal. These data suggest that midodrine is not effective in preventing hepatorenal syndrome type 2 recurrence.
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Abstract
Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.
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Storm C, Bernhardt WM, Schaeffner E, Neuhaus R, Pascher A, Neuhaus P, Hasper D, Frei U, Kahl A. Immediate Recovery of Renal Function After Orthotopic Liver Transplantation in a Patient With Hepatorenal Syndrome Requiring Hemodialysis for More Than 8 Months. Transplant Proc 2007; 39:544-6. [PMID: 17362778 DOI: 10.1016/j.transproceed.2006.12.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Severe liver dysfunction may lead to impairment of renal function without an underlying renal pathology. This phenomenon is called hepatorenal syndrome (HRS), which is associated with a poor prognosis showing a median survival of less than 2 months if renal replacement therapy is necessary. Liver transplantation is the best therapeutic option to regain renal function, but because of poor survival, these patients often die before transplantation. Herein we report a 37-year-old patient with ethyl-toxic liver cirrhosis who underwent hemodialysis due to HRS type I for more than 8 months. After living donor liver transplantation, diuresis immediately resumed, renal function soon recovered, and intermittent hemodialysis was stopped at 18 days after transplantation. Renal function was stable with a serum creatinine <2 mg/dL during the last 5 years posttransplantation. As far as we know, only a few cases of an anuric patient suffering from HRS have been reported with a survival beyond 8 months and full recovery of renal function after liver transplantation. This underlined that renal replacement therapy in HRS should be considered as a possible bridging method to liver transplantation even for longer periods.
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Affiliation(s)
- C Storm
- Department of Nephrology and Medical intensive care, Charit-Campus Virchow, University Hospital of Humboldt-University Berlin, Berlin, Germany.
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Blaas S, Schneidewind A, Glück T, Salzberger B. Acute renal failure in HIV patients with liver cirrhosis receiving tenofovir: a report of two cases. AIDS 2006; 20:1786-7. [PMID: 16931948 DOI: 10.1097/01.aids.0000242830.27990.93] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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