Chronic Kidney Disease After Liver Transplantation for Acute Liver Failure Is Not Associated With Perioperative Renal Dysfunction

Renal dysfunction of acute liver failure (ALF) may have distinct pathophysiological mechanisms to hepatorenal syndrome of cirrhosis. Yet, the impact of perioperative renal function on posttransplant renal outcomes in ALF patients specifically has not been established. The aims of this study were ( 1 ) to describe the incidence and risk factors for chronic renal dysfunction following liver transplantation for ALF and ( 2 ) to compare renal outcomes with age–sex‐matched patients transplanted for chronic liver disease. This was a single‐center study of 101 patients transplanted for ALF. Fifty‐three‐and‐a‐half percent had pretransplant acute kidney injury and 64.9% required perioperative renal replacement therapy. After transplantation the 5‐year cumulative incidence of chronic kidney disease (eGFR <60 mL/min/1.73 m²) was 41.5%. There was no association between perioperative acute kidney injury (p = 0.288) or renal replacement therapy (p = 0.134) and chronic kidney disease. Instead, the independent predictors of chronic kidney disease were older age (p = 0.019), female gender (p = 0.049), hypertension (p = 0.031), cyclosporine (p = 0.027) and nonacetaminophen‐induced ALF (p = 0.039). Despite marked differences in the perioperative clinical condition and survival of patients transplanted for ALF and chronic liver disease, renal outcomes were the same. In conclusion, in patients transplanted for ALF the severity of perioperative renal injury does not predict posttransplant chronic renal dysfunction.     

Hyperlipidemia Is Associated With Accelerated Chronic Kidney Disease Progression After Lung Transplantation

Hyperlipidemia is associated with faster progression of chronic kidney disease (CKD) in the general public. We sought to investigate this association after lung transplantation. Data was retrospectively collected on 230 lung recipients transplanted between January 1997 and December 2003. Estimated glomerular filtration rates (eGFR) and lipid levels were recorded at regular intervals posttransplant. Independent associations between lipid levels early posttransplant and pertinent renal endpoints were investigated. Baseline LDL was 110 ± 35 mg/dL and remained unchanged at 6 months. A faster decline in eGFR was seen in those with 6 month LDLs > versus < the mean level of 110 mg/dL (p = 0.05). By 6 months posttransplant eGFRs were lower in the 6 month LDL > versus < 110 mg/dL group (53 ± 23 vs. 62 ± 29 mL/min/1.73 m², p = 0.01), a difference that persisted at 60 months (39 ± 24 vs. 73 ± 57 mL/min/1.73 m², p = 0.05). On univariate analysis, a 6 month LDL in the highest quartile, i.e. >140 mg/dL, predicted faster progression to CKD, defined as declining to an eGFR < 30 mL/min/1.73 m² (HR 1.5, p = 0.01). This finding persisted in the multivariate Cox-proportional model (HR 1.4, p = 0.02). Hyperlipidemia predicts faster decline in renal function after lung transplant. Prospective trials are needed to confirm this finding.     

Heme Oxygenase-1 Genotype of the Donor Is Associated With Graft Survival After Liver Transplantation

Heme oxygenase-1 (HO-1) has been suggested as a cytoprotective gene during liver transplantation. Inducibility of HO-1 is modulated by a (GT)_n polymorphism and a single nucleotide polymorphism (SNP) A(-413)T in the promoter. Both a short (GT) _n allele and the A-allele have been associated with increased HO-1 promoter activity. In 308 liver transplantations, we assessed donor HO-1 genotype and correlated this with outcome variables. For (GT) _n genotype, livers were divided into two classes: short alleles (<25 repeats; class S) and long alleles (≥25 repeats; class L). In a subset, hepatic messenger ribonucleic acid (mRNA) expression was correlated with genotypes. Graft survival at 1 year was significantly better for A-allele genotype compared to TT-genotype (84% vs. 63%, p = 0.004). Graft loss due to primary dysfunction (PDF) occurred more frequently in TT-genotype compared to A-receivers (p = 0.03). Recipients of a liver with TT-genotype had significantly higher serum transaminases after transplantation and hepatic HO-1 mRNA levels were significantly lower compared to the A-allele livers (p = 0.03). No differences were found for any outcome variable between class S and LL-variant of the (GT) _n polymorphism. Haplotype analysis confirmed dominance of the A(-413)T SNP over the (GT) _n polymorphism. In conclusion, HO-1 genotype is associated with outcome after liver transplantation. These findings suggest that HO-1 mediates graft survival after liver transplantation.     

Clinical and Plasma Proteomic Markers Correlating With Chronic Kidney Disease After Liver Transplantation

Chronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristics and biomarkers diagnostic of CKD to enable early diagnosis allowing preemptive interventions, as well as mechanistic insights into the progression from kidney injury to irreversible kidney failure. We analyzed 342 patients who had baseline glomerular filteration rate (GFR) >60 at the time of LT and are now >3 years post‐LT. Risk factors for post‐LT CKD were compared between three different groups defined by current GFR: >90 (n = 40), 60–90 (n = 146) and <60 (n = 156) mL/min. Age, cyclosporine use and pre‐LT GFR were independently associated with new onset CKD. A subset (n = 64) without viral/immune disease or graft dysfunction underwent multianalyte plasma proteomic evaluations for correlation with CKD. Plasma proteomic analysis of two independent cohorts, test (n = 22) and validation (n = 42), identified 10 proteins highly associated with new onset CKD. In conclusion, we have identified clinical characteristics and a unique plasma proteomic signature correlating with new onset CKD after LT. These preliminary results are currently being validated in a prospective, multicenter study to determine if this signature precedes the onset of CKD and resolves with early interventions aimed at preserving kidney function .     

Renal Recovery After Liver Transplantation Alone in Patients With Liver Cirrhosis and Severe Chronic Kidney Disease With Normal Kidney Size

BackgroundMost guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with liver cirrhosis (LC) and severe chronic kidney disease (CKD) over liver transplantation alone (LTA). CKD, however, is not irreversible. This study evaluates the reversibility of kidney disease after LTA based on kidney size.Materials and methodsIn this single-center retrospective study, we classified 90 patients with LC and severe CKD into 3 groups: the normal kidney (NK)-LTA group (n=39), small kidney (SK)-LTA group (both kidneys <9 cm at the time of LTA, n=40), and SK-SLKT group (n=11).ResultsThe NK-LTA group had a lower percentage of hepatocellular carcinoma and a higher pre-liver transplantation (LT) estimated glomerular filtration rate. This group, however, was older, received livers from a higher percentage of deceased donors, and had a higher Child-Pugh score. Renal recovery, defined as the return of creatinine to their baseline, or a persistent change from baseline but not persistent (≥3 months) need for renal replacement therapy after LT, was found in 79% in the NK-LTA group, which was higher than 7.5% in the SK-LTA group. Renal and patient survival was found in 56% of the NK-LTA group, which was higher than 2.5% of the SK-LTA group.ConclusionsThere is a high percentage of renal recovery in the NK-LTA group, and accordingly, this does not justify SLKT, since this would result in a "waste" of kidneys. Therefore, KT after LT is recommended over SLKT for the LC patients with NK size.     

Kidney Disease After Allogeneic Hematopoietic Stem Cell Transplantation Is Associated With Decreased Physical Function

Objective/BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes and prognosis, but it has many complications and is associated with impaired physical function. To solve this problem, it is necessary to further analyze the factors that cause the decline in physical function. In the present study, we hypothesized that kidney disease following allo-HSCT would be associated with impaired physical function, in addition to conventional factors, and tested this hypothesis retrospectively.MethodsThirty-one patients who underwent allo-HSCT at the Department of Hematology in our hospital from January 2016 to October 2021 were included in the analysis. Correlation analysis and stepwise multiple regression analysis with change in 30-second sit to stand test (Δ30-s STS) as the dependent variable were performed to identify predictors of physical function decline from pretransplant to discharge.ResultsThe mean age of participants was 43.9 years (SD = 11.8), the mean time from transplant to discharge was 103.1 days (SD = 35.0), and approximately 30% of patients had kidney disease following allo-HSCT. All patients were ambulatory and independent at discharge, but 30-s STS was significantly reduced (P < .001). Among various factors, age (β = ?0.464, P < .05), total corticosteroid dose (β = ?0.380, P < .05), and kidney disease after allo-HSCT (β = ?0.307, P < .05) were the independent predictors of Δ30-s STS (R² = 0.592, adjusted R² = 0.547, F = 13.072, P < .01).ConclusionKidney disease after allo-HSCT is one of the factors that may contribute to poor physical function, and patients who experience this condition may require additional follow-up to improve physical function.     

Living Donor Liver Transplantation Alone Is Not Inferior to Combined Kidney Liver Transplant for Cirrhotic Patients With Chronic Kidney Disease

BackgroundChronic kidney disease (CKD) is common in patients with chronic liver disease (CLD) as is acute kidney injury (AKI). The differentiation between CKD vs AKI is often difficult and sometimes the both may coexist. A combined kidney–liver transplant (CKLT) may result in a kidney transplant in patients whose renal function is likely to recover or at least who have stable renal function post-transplant. We retrospectively enrolled 2742 patients who underwent living donor liver transplant at our center from 2007 to 2019.MethodsThis audit was carried out in liver transplant recipients with CKD 3 to 5 who underwent either liver transplant alone (LTA) or CKLT to look at outcomes and long-term evolution of renal function. Forty-seven patients met the medical eligibility criteria for CKLT. Of the 47 patients, 25 underwent LTA and the rest 22 underwent CKLT. The diagnosis of CKD was made according to the Kidney Disease: Improving Global Outcomes classification.ResultsPreoperative renal function parameters were comparable between the 2 groups. However, CKLT patients had significantly lower glomerular filtration rates (P = .007) and higher proteinuria (P = .01). Postoperatively, renal function, and comorbidities were comparable between the 2 groups. Survival was similar at 1, 3, and 12 months, respectively (log-rank; P = .84, = .81, and = .96, respectively). At the end of the study period, 57% of patients who survived in LTA groups had stabilized renal function (Creatinine = 1.8 ± 0.6 mg/dL).ConclusionsLiver transplant alone is not inferior to CKLT in living donor situations. Renal dysfunction is stabilized in the long term whereas long-term dialysis may be carried out in others. Living donor liver transplantation alone is not inferior to CKLT for cirrhotic patients with CKD.     

Recipient CTLA-4 +49 G/G Genotype Is Associated with Reduced Incidence of Acute Rejection After Liver Transplantation

The aim of this pilot study was to investigate whether acute rejection after liver transplantation is associated with known single-nucleotide polymorphisms (SNPs) in the CD86- and CTLA-4 genes of liver-transplant donors and recipients. Single nucleotide polymorphisms were determined in 135 liver transplant recipients and in 73 donors. Acute rejection was not associated with CD86 + 1057 G/A genotype distributions in donors and in recipients. In univariate analysis recipient CTLA-4 -318 G/T and + 49 A/G genotype distributions were both weakly associated with acute rejection. Multivariate analysis revealed that the CTLA-4 + 49 SNP, but not the -318 SNP, was independently of other risk factors associated with acute rejection. Only one out of 13 CTLA-4 + 49 G-homozygotes (8%) experienced acute rejection(s) compared with 40% of A/A or A/G recipients. The CTLA-4 + 49 A/G SNP, which results in an amino acid substitution in the signal peptide of the protein, did not, however, affect intracellular expression or trafficking of CTLA-4 in T cells, nor soluble serum CTLA-4 concentrations of the liver transplant recipients. In conclusion, this pilot study suggests that liver transplant recipients homozygous for CTLA-4 + 49 G have a reduced risk of acute rejection.     

Collectin Liver 1 and Collectin Kidney 1 of the Lectin Complement Pathway Are Associated With Mortality After Kidney Transplantation

Kidney transplanted patients still have significantly higher mortality compared with the general population. The innate immune system may play an important role during periods, with suppression of the adaptive immune system. In the present study, two soluble pattern recognition molecules of the innate immune system were investigated, collectin liver 1 (CL‐L1) and collectin kidney 1 (CL‐K1). Potential associations of their pretransplant levels and long‐term graft and recipient survival were examined. The levels of CL‐L1 and CL‐K1 were measured at the time of transplantation in 382 patients (≥17 years) transplanted in 2000–2001. The cohort was subsequently followed until December 31, 2014. Data on patient and graft survival were obtained from the Norwegian Renal Registry. Both high CL‐L1 (≥376 ng/mL) and high CL‐K1 (≥304 ng/mL) levels were significantly associated with overall mortality in multivariate Cox analyses with hazard ration (HR) 1.50, 95% confidence interval (CI) 1.09–2.07, p = 0.013 and HR 1.43, 95% CI 1.02–1.99, p = 0.038, respectively. Moreover, high CL‐K1 levels were significantly associated with cardiovascular mortality. No association between measured biomarkers and death‐censored graft loss was found. Finally, there was a significant correlation between these two collectins, r = 0.83 (95% CI 0.80–0.86). In conclusion, CL‐L1 and CL‐K1 were significantly associated with mortality in kidney transplant recipients.     

CC Genotype at rs12979860 of IL28B Is Associated With Lower Risk of New-onset Diabetes After Transplantation in Adult Patients With Liver Transplantation for Hepatitis C Cirrhosis

IntroductionNew-onset diabetes mellitus after transplantation (NODAT) in patients undergoing liver transplantation (LT) for hepatitis C virus (HCV)-related cirrhosis is associated with more aggressive HCV recurrence on the graft, rapid progression of fibrosis, and lower rate of sustained viral response to antiviral therapy. The CC genotype at rs12979860 of the IL28B is associated with greater rates of spontaneous clearance of HCV and response to antiviral therapy. IL28B acts on the interferon-stimulated genes through the JAK-STAT pathway, which is related to the development of insulin resistance. The aim of this study was to investigate whether IL28B rs12979860 polymorphism is associated with the development of NODAT after LT for cirrhosis owing to HCV infection.MethodsWe analyzed 99 patients (age, 52.7 ± 9.4 years; 70% male) who underwent LT for HCV-related cirrhosis, with ≥1 year of follow-up and with available DNA sample. NODAT was defined starting from the sixth month after LT, according to the international consensus guidelines. Genotyping was carried out by real-time polymerase chain reaction and analysis of the melting temperature with the LightCycler 480 system.ResultsTwenty-eight patients (28.3%) developed NODAT. CC genotype at rs12979860 of IL28B was associated with a lesser incidence of NODAT versus non-CC genotypes (P = .05; odds ratio, 0.31; 95% CI, 0.11–0.92). We did not find any association between NODAT and age at transplantation, gender, pretransplant body mass index, presence of hepatocellular carcinoma, type of initial immunosuppression (cyclosporine, tacrolimus or corticosteroids) or acute rejection treated with steroids.ConclusionThe CC genotype at rs12979860 of IL28B is a protective factor for NODAT in patients with LT for HCV-related cirrhosis.     

Systemic Immune-Inflammatory Marker of High Meld Patients Is Associated With Early Mortality After Liver Transplantation

The scarcity of deceased donor livers has led to allocation of grafts to only the most seriously ill patients with a high Model for End-Stage Liver Disease (MELD) score, which has resulted in a high mortality rate after deceased donor liver transplantation (DDLT). The aim of this study is to identify risk factors for posttransplant mortality and thereby reduce futile outcomes in DDLT. Between 2013 and 2019, 57 recipients with MELD scores ≥30 underwent DDLT in our center. We retrieved data and identified the risk factors for 90-day posttransplant mortality. The perioperative clinical and laboratory parameters of patients who did or did not survive for 90 days were subjected to logistic regression analysis. Twelve patients died within 90 days. Results of univariate analysis indicated that the differences in patient survival were determined by the amount of intraoperative platelets transfused, the presence of posttransplant septicemia, and systemic immune-inflammation index (SII) at the time of listing with MELD scores ≥30. Multivariate analysis revealed that an SII ≥870 (× 10⁹/L) and posttransplant septicemia were independent risk factors for 90-day mortality. Twenty-two patients had SIIs ≥870, and 13 of these patients had posttransplant septicemia. Of the 13 patients, 90-day mortality occurred in 10 cases. However, in 35 patients with SIIs <870, 90-day mortality due to posttransplant septicemia was recorded only in 1 patient. In conclusion, a preoperative SII ≥870 in a patient with a high MELD score may be a significant risk factor for early posttransplant mortality. Because posttransplant septicemia in patients with high SIIs can lead to fatality, a more intensive effort to prevent infection is needed for patients undergoing DDLT carrying such risk factors to avoid futile liver transplantation.     

Impact of Abdominal Aortic Calcification on Chronic Kidney Disease After Liver Transplantation: A Retrospective Study

BackgroundWith improved graft and patient survival after liver transplantation (LT), the onset of late complications, such as renal dysfunction, has become a problem. In this study, we aimed to investigate abdominal aortic calcification (AAC), a potential indicator of systemic atherosclerosis, and evaluate the relationship between preoperative AAC and postoperative chronic kidney disease (CKD), as the latter might be a long-term complication after LT.MethodsAmong the 184 LTs performed at our center between 2008 and 2021, 110 LTs with normal renal function (estimated glomerular filtration rate [eGFR] 60 mL/min per 1.73 m²) before surgery were included. These were divided into high- (≥100 mm³) and low-AAC groups (<100 mm³) consisting of 51 and 59 patients, respectively. The AAC volume was automatically calculated for calcifications located in the abdominal aorta using the Agatston method.ResultsThe high-AAC group was older, consisted of more men, and had lower preoperative creatinine and eGFR levels. No significant difference in the onset of postoperative CKD was found between the 2 groups. However, the cumulative incidence of postoperative CKD was significantly higher in the high-AAC group compared with the low-AAC group. Multivariate analysis of postoperative CKD using the Cox proportional hazards model showed significant differences in preoperative AAC ≥100 mm³, recipient age ≥50 years, and preoperative eGFR <75 mL/min per 1.73 m².ConclusionsThe development of postoperative CKD should be monitored in liver transplant recipients despite normal preoperative renal function. Our study suggests that preoperative AAC may influence postoperative renal dysfunction.     

Long-term Follow-up of Living Kidney Donors With Chronic Kidney Disease at 1 Year After Nephrectomy

Background

Although renal function recovery of living kidney donors has been reported in a number of studies, many patients show poor recovery, and the long-term prognosis of these patients has not been well studied. In this investigation we explored the long-term prognosis of renal function in patients with chronic kidney disease (CKD) at 1 year after nephrectomy.

肝肾联合移植术后并发Kaposi''''s肉瘤(附1例报告)

目的:探讨器官移植受者并发Kaposi's肉瘤的发生率、原因及诊治.方法:回顾分析1例肝肾联合移植术后合并Kaposi's肉瘤患者的临床诊治经过.结果:患者于术后17个月起病,首发症状为腹膜后淋巴结肿大,随后出现腹股沟淋巴结肿大及腹部红褐色斑丘疹,经病理活检确诊,CsA减量联合小剂量化疗,起病半年死亡.结论:Kaposi's肉瘤是器官移植受者的常见并发症,发病常与免疫抑制过度及HHV-8病毒感染有关,诊断依赖于组织病理学检查,予小剂量化疗及减少免疫抑制剂的用量,临床愈后差.     

Human Polyomavirus Is Associated With Earlier Onset of Upper Urinary Tract Urothelial Carcinoma in Patients After Kidney Transplantation

Objectives

Polyomavirus has been reported to be oncogenic due to viral integration into the human genome. A relatively high prevalence of upper urinary tract urothelial carcinoma (UTUC) was noted after kidney transplantation (KT) in Taiwan. However, little was known about the impact of polyomavirus on the urothelial cancer behavior. Therefore, the aim of this study is to analyze the characteristics of polyomavirus-related UTUC after KT.

Repeated Contrast Administration Is Associated With Low Risk of Postcontrast Acute Kidney Injury and Long‐Term Complications in Patients With Severe Chronic Kidney Disease

Patients with chronic kidney disease (CKD) frequently require radiographic examinations. We investigated the impact of repeated contrast administrations on short‐ and long‐term kidney function and mortality in kidney transplantation candidates. In a prospective study, 81 predialysis transplantation candidates underwent computed tomography angiography (CTA) and invasive coronary angiography (ICA) as part of a pretransplant cardiovascular evaluation. Postcontrast plasma creatinine (P‐creatinine) changes were compared with a precontrast control period. We identified postcontrast acute kidney injury (AKI) in 10 patients (13%) after CTA and in two patients (3%) after ICA. Compared with the control period, relative changes in P‐creatinine were significantly higher after CTA (p < 0.001) and ICA (p < 0.01). Diabetic kidney failure (p < 0.05) and contrast dose >0.8 mL/kg (p < 0.001) were associated with increases in P‐creatinine. All cases of postcontrast AKI were reversible, and we found no differences between the progression rates of the kidney failure during 12 months before and after contrast exposure (p = 0.56). In a Cox regression analysis, creatinine changes after CTA or ICA were not associated with increased need for dialysis treatment or mortality. Contrast exposure and transient postcontrast AKI did not increase the risk of accelerated CKD progression or the time to initiation of dialysis or death.     

Association between transforming growth factor beta-1 + 869 T/C polymorphism and acute rejection of solid organ allograft: A meta-analysis and systematic review

BackgroundTransforming growth factor beta-1(TGFB1) is involved in the acute rejection (AR) episodes of solid organ transplant recipients. However, results from published studies on the association between donor/recipient TGFB1 + 869 T/C polymorphism and AR risk are conflicting and inconclusive.MethodsPUBMED, EMBASE, CNKI and Wanfang Database were searched to identify eligible studies investigating the association between donor/recipient TGFB1 + 869 T/C polymorphism and AR risk. Statistical analysis was performed by using STATA 10.0.ResultsA total of 29 studies were included. Overall, the donor TGFB1 + 869 T/C polymorphism was significantly associated with AR risk in heterozygote comparison (CT vs. TT: OR = 1.67, 95%CI, 1.17–2.39; P heterogeneity = 0.285) and dominant model (CC vs. TC/TT: OR = 1.47, 95%CI, 1.05–2.06; P heterogeneity = 0.445). In addition, subgroup analysis revealed that CT variant (CT vs. TT: OR = 1.97, 95%CI, 1.20–3.25; P heterogeneity = 0.777) and CC/CT genotype (CC/CT vs. TT: OR = 1.72, 95%CI, 1.07, 2.78; P heterogeneity = 0.619) within donors contributed to higher risk of AR in recipients administrated with CsA or FK506, compared with those applied only CsA. On the other hand, no significant association between recipient TGFB1 + 869 T/C polymorphism and AR was detected in all genetic models.ConclusionsThis meta-analysis and systematic review suggested that donor TGFB1 + 869 T/C polymorphism was significantly associated with AR of solid organ transplant recipients, and especially among patients in CsA/FK 506 group compared with those in CsA group.     

Antibodies to K‐α 1 Tubulin and Collagen V Are Associated With Chronic Rejection After Lung Transplantation

Bronchiolitis obliterans syndrome (BOS), the clinical correlate of chronic rejection after lung transplantation, is the leading obstacle to better long‐term outcomes. We previously instituted a clinical protocol to screen for donor‐specific human leukocyte antigen (HLA) antibodies (DSA) and a preemptive antibody‐directed therapy protocol consisting of rituximab and/or intravenous immune globulin. In this study, we retrospectively analyzed serum samples from lung transplant recipients (n = 108) for antibodies to self‐antigens (K‐α 1 tubulin and collagen V) before and after antibody‐directed therapy and correlated the results with the subsequent development of BOS. Seventy‐two of the 108 recipients developed antibodies to self‐antigens. There was a correlation between the development of antibodies to self‐antigens and DSA. Sixteen of the 54 patients who had antibodies to self‐antigens and were treated with antibody‐directed therapy cleared the antibodies, and they were significantly less likely to develop BOS than those who had persistent antibodies. Furthermore, those who cleared DSA after treatment but had persistent antibodies to self‐antigens were significantly more likely to develop BOS than those who cleared these antibodies. We conclude that antibodies to self‐antigens are an important risk factor for the development of BOS.