|
1
|
He Z, Lin Y, Dong S, Ke Q, Zheng S, Ling Q. Development and validation of a nomogram model for predicting chronic kidney disease after liver transplantation: a multi-center retrospective study. Sci Rep 2023; 13:11380. [PMID: 37452094 PMCID: PMC10349045 DOI: 10.1038/s41598-023-38626-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 07/11/2023] [Indexed: 07/18/2023] Open
Abstract
Chronic kidney disease (CKD) is a frequent complication after liver transplantation (LT) and associated with poor prognosis. In this study, we retrospectively analyzed 515 adult patients who underwent LT in our center. They were randomly divided into a training set (n = 360) and an internal test set (n = 155). Another 118 recipients in other centers served as external validation set. Univariate and multivariate COX regression analysis were used to determine risk factors. A nomogram model was developed to predict post-LT CKD. The incidence of post-LT CKD in our center was 16.9% (87/515) during a median follow-up time of 22.73 months. The overall survival of recipients with severe CKD (stage IV and V) were significantly lower than those with non or mild CKD (stage III) (p = 0.0015). A nomogram model was established based on recipient's age, anhepatic phase, estimated glomerular filtration rate and triglyceride levels at 30 days after LT. The calibration curves for post-LT CKD prediction in the nomogram were consistent with the actual observation in both the internal and external validation set. In conclusion, severe post-LT CKD resulted in a significantly reduced survival in liver recipient. The newly established nomogram model had good predictive ability for post-LT CKD.
Collapse
Affiliation(s)
- Zenglei He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yimou Lin
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Siyi Dong
- China Liver Transplant Registry, Hangzhou, 310003, China
| | - Qinghong Ke
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Qi Ling
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
| |
Collapse
|
|
2
|
Okushin K, Yamana H, Tateishi R, Sato M, Tsutsumi T, Matsui H, Fushimi K, Yasunaga H, Koike K, Fujishiro M. Treatment and outcome of hepatorenal syndrome in Japan: a retrospective cohort study using a national inpatient database. BMC Gastroenterol 2023; 23:218. [PMID: 37353737 DOI: 10.1186/s12876-023-02858-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 06/18/2023] [Indexed: 06/25/2023] Open
Abstract
BACKGROUND Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database. METHODS Patients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups' baseline patient characteristics and treatments were compared. RESULTS The mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child-Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis. CONCLUSIONS HRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice.
Collapse
Affiliation(s)
- Kazuya Okushin
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Yamana
- Data Science Center, Jichi Medical University, Shimotsuke, Japan
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeya Tsutsumi
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Kanto Central Hospital, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| |
Collapse
|
|
3
|
Ting JA, Induruwage D, Yoshida EM, Dhruve M, Zalunardo NY. Albuminuria post-liver transplant is a predictor of kidney disease progression and mortality. CANADIAN LIVER JOURNAL 2023; 6:2-13. [PMID: 36908578 PMCID: PMC9997516 DOI: 10.3138/canlivj-2022-0019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 06/05/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND: Albuminuria is a marker of chronic kidney disease (CKD) associated with an increased risk of end-stage kidney disease (ESKD) and mortality in the general population, but it is uncertain whether the same association exists in liver transplant (LT) recipients. This study examined the association between albuminuria and kidney failure and mortality in LT recipients.METHODS: Retrospective cohort study of 294 adults who received a LT between January 1, 1989, and December 31, 2011, in British Columbia, Canada. Cox multivariable regression was used to determine the association between ACR and a primary combined outcome of mortality, doubling of serum creatinine, or ESKD; and a secondary outcome of a decrease in estimated glomerular filtration rate (eGFR) ≥30%. RESULTS: At baseline, mean eGFR was 67 (SD 20.9) mL/min/1.73 m2, and 10% had severe albuminuria (ACR >30 mg/mmol). The primary outcome occurred in 20.4% (60) of patients and was associated with ACR >30 mg/mmol (HR 2.77, 95% CI 1.28-6.04; P = 0.01). A decline in eGFR ≥30% occurred in 21.8% (64) of patients, and was associated with ACR >30 mg/mmol (HR 4.77, 95% CI 2.31-9.86; P < 0.0001). CONCLUSIONS: Severe albuminuria (ACR >30 mg/mmol) was associated with an increased risk of loss of kidney function and mortality after LT. Prospective studies are needed to determine if specific interventions directed at reducing albuminuria can improve long-term outcomes in LT recipients.
Collapse
Affiliation(s)
- Julie Anne Ting
- Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Miten Dhruve
- Division of Nephrology, Michael Garron Hospital, Toronto, Ontario, Canada
| | - Nadia Y Zalunardo
- Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
| |
Collapse
|
|
4
|
Rasaei N, Malekmakan L, Mashayekh M, Gholamabbas G. Chronic Kidney Disease Following Liver Transplant: Associated Outcomes and Predictors. EXP CLIN TRANSPLANT 2022; 21:93-103. [PMID: 36656117 DOI: 10.6002/ect.2022.0288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVES Liver transplant as a life-saving procedure in patients with end-stage liver disease may have some complications such as renal dysfunction. Improved postoperative management and immuno- suppressive therapy have increased long-term survival and thus increased late complications like chronic kidney disease. Our study aimed to investigate outcomes of chronic kidney disease in liver transplant recipients and the incidence, progression rates, and adjustable risk factors of chronic kidney disease after liver transplant. MATERIALS AND METHODS Related studies published in English were elicited from various international sources like the ISI Web of Science, PubMed/Medline, Google Scholar, and Scopus. RESULTS AND CONCLUSIONS Chronic kidney disease as a long-term complication is common in liver transplant recipients whose survival is affected by renal function. Risk assessment of renal function before liver transplant and some nonrenal causes of chronic kidney disease after transplant could help reduce the risks associated with future renal outcomes.
Collapse
Affiliation(s)
- Nakisa Rasaei
- From the Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | | | | |
Collapse
|
|
5
|
Teo VXY, Heng RRY, Tay PWL, Ng CH, Tan DJH, Ong Y, Tan EY, Huang D, Vathsala A, Muthiah M, Tan EXX. A meta-analysis on the prevalence of chronic kidney disease in liver transplant candidates and its associated risk factors and outcomes. Transpl Int 2021; 34:2515-2523. [PMID: 34773291 DOI: 10.1111/tri.14158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 10/20/2021] [Accepted: 11/07/2021] [Indexed: 12/15/2022]
Abstract
Pre-liver transplant (LT) chronic kidney disease (CKD) has emerged as a leading cause of post-operative morbidity. We aimed to report the prevalence, associated risk factors, and clinical outcomes in patients with pre-LT CKD. Meta-analysis and systematic review were conducted for included cohort and cross-sectional studies. Studies comparing healthy and patients with s pre-LT CKD were included. Outcomes were assessed with pooled hazard ratios. 15 studies were included, consisting of 82,432 LT patients and 26,754 with pre-LT CKD. Pooled prevalence of pre-LT CKD was 22.35% (CI: 15.30%-32.71%). Diabetes mellitus, hypertension, viral hepatitis, and non-alcoholic fatty liver disease, and older age were associated with increased risk of pre-LT CKD: (OR 1.72 CI: 1.15-2.56, P = 0.01), (OR 2.23 CI: 1.76-2.83, P < 0.01), (OR 1.09; CI: 1.05-1.13, P < 0.01), (OR 1.73; CI: 1.10-2.71 P = 0.03), and (MD: 2.92 years; CI: 1.29-4.55years; P < 0.01) respectively. Pre-LT CKD was significantly associated with increased mortality (HR 1.38; CI: 1.2-1.59; P < 0.01), post-LT end-stage renal disease and post-LT CKD. Almost a quarter of pre-LT patients have CKD and it is significantly associated with post-operative morbidity and mortality. However, long-term outcomes remain unclear due to a lack of studies reporting such outcomes.
Collapse
Affiliation(s)
- Vanessa Xin Yi Teo
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Ryan Rui Yang Heng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Phoebe Wen Lin Tay
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Yuki Ong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - En Ying Tan
- Department of Medicine, National University Hospital, Singapore
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Anantharaman Vathsala
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Nephrology, Department of Medicine, National University Hospital, Singapore.,Kidney and Pancreas Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| |
Collapse
|
|
6
|
Herrero JI, Cuervas-Mons V, Gómez-Bravo MÁ, Fabregat J, Otero A, Bilbao I, Salcedo MM, González-Diéguez ML, Fernández JR, Serrano MT, Jiménez M, Rodrigo JM, Narváez I, Sánchez G. Prevalence and progression of chronic kidney disease after a liver transplant: a prospective, real-life, observational, two-year multicenter study. REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS 2018; 110:538-543. [DOI: 10.17235/reed.2018.5431/2017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
|
|
7
|
Modi RM, Patel N, Metwally SN, Mumtaz K. Outcomes of liver transplantation in patients with hepatorenal syndrome. World J Hepatol 2016; 8:999-1011. [PMID: 27648152 PMCID: PMC5002501 DOI: 10.4254/wjh.v8.i24.999] [Citation(s) in RCA: 9] [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: 04/28/2016] [Revised: 06/20/2016] [Accepted: 07/18/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include: (1) estimation of glomerular filtration rate of 30 mL/min or less for 4-8 wk; (2) proteinuria > 2 g/d; or (3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding long-term benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL/min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.
Collapse
|
|
8
|
Yoon No D, Lee KH, Lee J, Lee SH. 3D liver models on a microplatform: well-defined culture, engineering of liver tissue and liver-on-a-chip. LAB ON A CHIP 2015; 15:3822-37. [PMID: 26279012 DOI: 10.1039/c5lc00611b] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
The liver, the largest organ in the human body, is a multi-functional organ with diverse metabolic activities that plays a critical role in maintaining the body and sustaining life. Although the liver has excellent regenerative and recuperative properties, damages caused by chronic liver diseases or viral infection may lead to permanent loss of liver functions. Studies of liver disease mechanism have focused on drug screening and liver tissue engineering techniques, including strategies based on in vitro models. However, conventional liver models are plagued by a number of limitations, which have motivated the development of 'liver-on-a-chip' and microplatform-based bioreactors that can provide well-defined microenvironments. Microtechnology is a promising tool for liver tissue engineering and liver system development, as it can mimic the complex in vivo microenvironment and microlevel ultrastructure, by using a small number of human cells under two-dimensional (2D) and three-dimensional (3D) culture conditions. These systems provided by microtechnology allow improved liver-specific functions and can be expanded to encompass diverse 3D culture methods, which are critical for the maintenance of liver functions and recapitulation of the features of the native liver. In this review, we provide an overview of microtechnologies that have been used for liver studies, describe biomimetic technologies for constructing microscale 2D and 3D liver models as well as liver-on-a-chip systems and microscale bioreactors, and introduce applications of liver microtechnology and future trends in the field.
Collapse
Affiliation(s)
- Da Yoon No
- Department of Biomedical Engineering, College of Health Science, Korea University, Anamro 145, Seongbuk-gu, Seoul 136-701, Republic of Korea.
| | | | | | | |
Collapse
|
|
9
|
Varo E, Bañares R, Guilera M. Underestimation of chronic renal dysfunction after liver transplantation: ICEBERG study. World J Transplant 2015; 5:26-33. [PMID: 25815269 PMCID: PMC4371159 DOI: 10.5500/wjt.v5.i1.26] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 02/10/2015] [Accepted: 03/09/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To compare prevalence of chronic renal dysfunction (CRD) according to serum creatinine (sCr) vs estimated glomerular filtration rate (eGFR) among maintenance liver transplant patients.
METHODS: The ICEBERG study was an observational, retrospective, cross-sectional, and multicenter study. Consecutive adult patients (aged 18 years or older) with liver transplantation (LT) performed at least two years previously were recruited. Multi-organ transplant recipients were excluded. Chronic renal dysfunction was defined according to sCr based criteria in routine clinical practice (≥ 2 mg/dL) and eGFR using MDRD-4 equation (< 60 mL/min per 1.73 m2). Agreement between sCr definition and eGFR assessment was evaluated using the Kappa index. Cox regression analysis was applied to identify predictive factors for developing CRD after LT.
RESULTS: A total of 402 patients were analyzed (71.6% males). Mean ± SD age at transplant was 52.4 ± 9.8 years. Alcoholic cirrhosis without hepatocellular carcinoma was the most common reason for LT (32.8%). Mean time since LT was 6.9 ± 3.9 years. Based on sCr assessment, 35.3% of patients (95%CI: 30.6-40.0) had CRD; 50.2% (95%CI: 45.3-55.1) according to eGFR. In 32.2% of cases, sCr assessment had underestimated CRD. Multivariate analysis showed the following factors associated with developing CRD: eGFR < 60 mL/min per 1.73 m2 at three months post-transplant [hazard ratio (HR) = 4.76; 95%CI: 2.78-8.33; P < 0.0001]; calcineurin inhibitor use (HR = 2.31; 95%CI: 1.05-5.07; P = 0.0371); male gender (HR = 1.98; 95%CI: 1.09-3.60; P = 0.0260); and ≥ 10 years post-transplantation (HR = 1.95; 95%CI: 1.08-3.54; P = 0.0279).
CONCLUSION: Seven years after LT, CRD affected half our patients, which was underestimated by sCr. An eGFR < 60 mL/min per 1.73 m2 three months post-LT was predictive of subsequent CRD.
Collapse
|