Recovery of renal function in liver transplant alone versus combined liver kidney transplantation: analysis from the NHSBT UK registry

Introduction and Aims: Recovery of renal function after liver transplantation is strongly influenced by pretransplant degree and duration of renal insufficiency, despite imprecise methods for measuring renal dysfunction. Indications for combined liver-kidney transplantation (CLKT) have been defined, but these are still under debate and hepatorenal syndrome (HRS) is a particularly challenging condition given the hardly predictable spontaneous improvement with liver transplant alone (LTA). Methods: We analysed data of 6035 patients (Jan 2001-Dec 2012) from NHSBT UK Transplant Registry. Renal function at 1 years after transplantation was compared between CLKT and LTA with stratification on the basis of glomerular filtration rate (eGFR) at transplant (KDIGO Guidelines) and treatment with renal replacement therapy (RRT). Renal function post-transplantation was classified as eGFR >60, between 59-30 and <30 ml/min/1.73m2, the latter identified as non recovery of renal function. Univariate and multivariable analysis were performed. Results: 5912 patients (98.0%) underwent liver transplant alone (LTA) and 123 (2.0%) patients received a CLKT. 305 (5.2%) of the LTA group were on RRT at time of transplantation, compared to 72 (58.5%) of the CKLT group. No patient with a MELD score <20 received RRT before transplant. No patients with eGFR ≥60 mL/min/1.73m2 received CLKT. 27% of patients receiving CLKT were diagnosed with pre-transplant glomerular/tubular kidney disease, 39% with polycystic disease and 34% were not specified. LTA patients on RRT were more frequently presenting ascites ( p<0.001), variceal bleeding ( p=0.002), higher MELD score ( p<0.001), higher INR ( p<0.001) and bilirubin at transplant ( p<0.001), suggesting the occurrence of HRS (data not available). Patients on RRT experience a significant difference of renal function recovery at 1 year post-transplant when receiving LTA versus CLKT, with the latter group experiencing a higher percentage of non-recovery ( p=0.001; table 1). This difference was not detected for other eGFR stratifications.The univariate analysis identified recipient age >50 years, female gender, RRT in patients with MELD >20, polycystic disease and diabetes as predictive factors for non-recovery of renal function in patients undergoing LTA. In a multivariable model including all clinically relevant variables simultaneously, the independent predictors of renal function non-recovery were female gender (HR 2.76; 95% CI 1.52-4.99, p=0.001), RRT in patients with MELD >20 (HR 3.62; 95% CI 1.44-9.08, p=0.006) and diabetes (HR 2.55; 95% CI 1.38-4.73, p=0.003). Conclusions: Recovery of renal function post-LTA is acceptable for patients with different stratifications of eGFR pre-transplant. RRT, female gender and diabetes may suggest to perform CLKT

Renal involvement in HCV related cirrhosis evidenced as glomerular and tubular derangement

Introduction and Aims: The relation between HCV infection and glomerular damage is well recognized, with evidences of negative impact on renal function. HCV replication in renal tubular cells on kidney biopsies has been reported but very limited data are available on HCV-mediated tubular damage. The aim of the study was to assess the presence of renal involvement (RI), glomerular or tubular, in patients with HCV cirrhosis. Methods: 98 patients with HCV cirrhosis Child Pugh-A were consecutively enrolled. Glomerular filtration rate (eGFR) was estimated with CKD-EPI 2009 equation. Urinary albumin/creatinine (ACR) and alpha1microglobulin/creatinine (a1MCR) ratios were calculated. Glomerular involvement was defined based on ACR>20μg/mg, tubular involvement based on a1MCR>14μg/mg plus fractional sodium excretion (FeNa)>1%. Urine concentration of Liver-type Fatty Acid-Binding Protein (L-FABP) and Kidney injury molecule-1 (KIM-1) were examined in morning midstream urine samples (ELISA) and the values normalized to urine creatinine concentration as expression of tubular derangement. Results: eGFR was ≥60 mL/min/1.73 m2 in 92 patients (93.8%) and between 45-59 mL/min/1.73 m2 in 6 patients (6.1%). Glomerular involvement was found in 19 patients (19.4%), tubular involvement in 31 patients (31.6%) and these co-occurred in 10 patients ( p=0.034). Patients with glomerular or tubular involvement, or both, considered as patients with RI, showed significantly lower eGFR values ( p=0.005) (Tab 1). A ROC curve was drafted and a cut point of 90 ml/min predicted RI (AUC: 0.700; sensitivity 63%, specificity 75%). Patients with RI were older, had higher ACR and a1MCR levels and exhibited a higher KDIGO stage (Tab 1). No association was found between RI and: HCV-RNA levels, liver stiffness and liver function tests. L-FABP and KIM-1 levels were significantly higher in patients with RI. Conclusions: Tubular and/or glomerular involvement is quite frequent in HCV cirrhotic patients, despite a normal eGFR. The evidence of tubular involvement suggests an alternative localization of HCV as renal disease

Nonalcoholic fatty liver disease and the kidney: a review

Nonalcoholic fatty liver disease (NAFLD) is associated with several extrahepatic manifestations such as cardiovascular disease and sleep apnea. Furthermore, NAFLD is reported to be associated with an increased risk of incident chronic kidney disease (CKD). Inflammation and oxidative stress are suggested to be the key factors involved in the inflammatory mechanisms and pathways linking NAFLD to CKD and are responsible for both the pathogenesis and the progression of CKD in NAFLD patients. This review aims to provide a more comprehensive overview of the association between CKD and NAFLD, also considering the effect of increasing severity of NAFLD. A PubMed search was conducted using the terms “non-alcoholic fatty liver disease AND kidney”. In total, 537 articles were retrieved in the last five years and 12 articles were included in the qualitative analysis. Our results showed that CKD developed more frequently in NAFLD patients compared to those without NAFLD. This association persisted after adjustment for traditional risk factors and according to the severity of NAFLD. Therefore, patients with NAFLD should be considered at high risk of CKD. Intensive multidisciplinary surveillance over time is needed, where hepatologists and nephrologists must act together for better and earlier treatment of NAFLD patients

Association between non-alcoholic fatty liver disease and obstructive sleep apnea

Background: Non-alcoholic fatty liver disease (NAFLD) is an emerging liver disease and currently the most common cause of incidental abnormal liver tests. The pathogenesis of NAFLD is multifactorial and many mechanisms that cause fatty liver infiltration, inflammation, oxidative stress and progressive fibrosis have been proposed. Obstructive sleep apnea (OSA) may be linked with the pathogenesis and the severity of NAFLD. Aim: To study the association between NAFLD and OSA considering also the efficacy of continuous positive airway pressure (CPAP) treatment. Methods: A PubMed search was conducted using the terms "non-alcoholic fatty liver disease AND (obstructive sleep apnea OR obstructive sleep disorders OR sleep apnea)". Research was limited to title/abstract of articles published in English in the last 5 years; animal and child studies, case reports, commentaries, letters, editorials and meeting abstracts were not considered. Data were extracted on a standardized data collection table which included: First author, publication year, country, study design, number of patients involved, diagnosis and severity of OSA, diagnosis of NAFLD, patient characteristics, results of the study. Results: In total, 132 articles were initially retrieved on PubMed search and 77 in the last five years. After removal of irrelevant studies, 13 articles were included in the qualitative analysis. There was a total of 2753 participants across all the studies with a mean age between 42 and 58 years. The proportion of males ranged from 21% to 87.9% and the mean body mass index ranged from 24.0 to 49.9 kg/m2. The results of this review showed an increased prevalence of NAFLD in patients with diagnosis of OSA, even in the absence of coexisting comorbidities such as obesity or metabolic syndrome. Furthermore, the severity of NAFLD is associated with the increase in OSA severity. Effective CPAP treatment, although not always decisive, may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions. Conclusion: In NAFLD patients, although asymptomatic, it is recommended to systematically perform polysomnography in order to early and better treat them before the development of potentially life threatening systemic dysfunctions

Acute kidney injury as delayed graft function in donation after circulatory death kidney transplantation: uk single centre study

Introduction and Aims: Delayed graft function (DGF) is a manifestation of acute kidney injury (AKI) traditionally related to cold ischaemia time, with characteristics unique to the kidney transplant (KT) process. It is defined as the need for dialysis within 7 days of the transplant and is associated with higher incidence of rejection, chronic graft dysfunction and premature graft loss after KT. Kidney transplantation from Donation after Circulatory Death (DCD) is a model with increased occurrence of DGF compared to Donation after Brain Death (DBD) and living donation (LD). This is likely to be related to the warm ischaemia sustained by the graft. Since the diagnostic criterion of DGF has shortfalls as dialysis is subjective and is a clinician-dependent decision, aim of the study is to assess the whole incidence of AKI, including DGF after KT in different models of ischaemia of the graft (DCD vs. DBD vs. LD) and to evaluate their impact on outcome. Methods: Retrospective single-centre study of 1042 patients who underwent KT (2007-2014). We considered: renal function pre-KT, daily within one week post-operatively, at 1, 4, 6, 9 months and 1, 3, 5, 8 years post-KT, characteristics of recipient, donor and graft, patient survival. AKI and DGF were defined on the basis of KDIGO Guidelines. Results: We considered 1042 KT patients (132 DCD, 414 DBD and 496 living). Analysis of the demographic and clinical characteristics showed no significant differences between DCD and DBD recipients, whereas there were significant differences between both DCD and DBD compared to LD in median age, race, HBV, HCV (only DBD), serum sodium, serum creatinine, GFR and dialysis. Preliminary analysis showed that DCD recipients had a significantly lower cold ischaemia time (CIT; p=0.0120) and higher incidence of AKI and DGF than DBD ( p<0.001), but in DBD the CIT had a positive association with the occurrence of DGF ( p=0.072). All results about incidence of AKI and DGF are reported in Table. No significant differences in patient’s survival were found between DCD vs. DBD vs. LD. AKI and DGF had no significant impact on survival. Conclusions: We demonstrate a higher incidence of post-KT DGF in DCD, despite similar baseline characteristics and a lower CIT, compared to DBD. For the first time we note that DCD recipients suffer a higher incidence of AKI stage 2-3 than DBD and LD. Further analysis should look at the incidence of chronic graft dysfunction and the association between AKI and DGF

Acute kidney injury and chronic kidney disease in donation after circulatory death liver transplantation: UK single centre study

Aim of the study is to assess the incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) after liver transplantation (LT) in DCD vs. DBD recipients. Methods: this is a retrospective single-centre study of 1151 patients who underwent LT from 2007 to 2014. Exclusion criteria: urgent (=66) and living donor (=7) LT. We considered: renal function pre-LT, daily within one week post-operatively, at 1, 3, 4, 6, 9 months and 1, 3, 5 years post-LT, characteristics of recipient, donor type, graft variables and indicators of initial graft function. AKI and CKD defined and classified on the basis of KDIGO Guidelines (2012). Results: we considered 1078 LT patients (830 DBD and 248 DCD). DBD recipients had a higher MELD (p=0.002) and pre-LT serum bilirubin level (p<0.001) than DCD but there were no differences in INR and serum creatinine values. DBD recipients had longer cold and recipient warm ischemia times than DCD (p<0.001 and p=0.018 respectively). The incidence of AKI was 57.9% (624/1078), of which 57.1% of DBD (474/830) vs. 60.5% of DCD (150/248). DCD recipients had a higher incidence of stage 3 AKI than DBD (20.6% vs. 12.7%, p=0.0197). Among patients with stage 3 AKI DCD had a higher cumulative incidence of CKD compared to DBD (SHR 1.6 (1.0-2.7), p=0.051). Conclusion: For the first time we showed that both DBD and DCD recipients suffer a similar degree of stage 1-2 of AKI, but the DCD experience more severe stage 3 AKI, which is associated with a higher incidence of CKD in the long-term follow-up

Gender disparities in vascular access and one-year mortality among incident hemodialysis patients: An epidemiological study in Lazio Region, Italy

(1) Background: Interest in gender disparities in epidemiology, clinical features, prognosis and health care in chronic kidney disease patients is increasing. Aims of the study were to evaluate the association between gender and vascular access (arteriovenous fistula (AVF) or central venous catheter (CVC)) used at the start of hemodialysis (HD) and to investigate the association between gender and 1-year mortality. (2) Methods: The study includes 9068 adult chronic HD patients (64.7% males) registered in the Lazio Regional Dialysis Register (Jan 2008–Dec 2018). Multivariable logistic regression models were used to investigate the associations between gender and type of vascular access (AVF vs. CVC) and between gender and 1-year mortality. Interactions between gender and socio-demographic and clinical variables were tested adding the interaction terms in the final model. (3) Results: Females were older, had lower educational level and lower rate of self-sufficiency compared to males. Overall, CVC was used in 51.2% of patients. Females were less likely to use AVF for HD initiation than males. 1354 out of 8215 (16.5%) individuals died at the end of the follow-up period. Interaction term between gender and vascular access was significant in the adjusted model. From stratified analyses by vascular access, OR female vs. male (AVF) = 0.65; 95% CI 0.48–0.87 and OR female vs. male (CVC) = 0.88; 95% CI 0.75–1.04 were found. (4) Conclusion: This prospective population-based cohort study in a large Italian Region showed that in females starting chronic HD AVF was less common respect to men. The better 1-year survival of females is more evident among those women with AVF. Reducing gender disparity in access to AVF represents a key point in the management of HD patients

Intraoperative hemodynamc profile of DCD liver transplantation

Cardiovascular instability after reperfusion of liver grafts is a well-recognised phenomenon in liver transplantation. In theory patients transplanted with DCD liver grafts might experience worse intra-operative hemodynamic variability and greater need of support with inotropes after reperfusion. In fact recipient selection for DCD livers remains often limited to candidates with HCC or low MELD as they could better withstand a severe reperfusion syndrome. Aim of this study was to depict the intra-operative cardiovascular profile after graft reperfusion of DCD grafts compared with DBD. From a prospectively held database of over 4400 liver transplants, 30 consecutive recipients of DBD grafts and 30 patients transplanted with DCD grafts in 2014 were selected. A retrospective analysis of their intraoperative hemodynamic and metabolic data and of inotropic support was conducted relative to donor and recipient characteristics. These were similar in both groups except for an expected higher donor risk index (2.84 vs. 1.85, p=0.001) and lower recipient MELD (12 vs. 16, p=0.009) in DCD group. With similar hemodynamic profile at the start of the operation for both patient groups, DCD recipients had a similar post reperfusion syndrome rate (10% vs. 13%, p> 0.05) a comparable inotrope and blood products requirement compared with DBD patients. After the arterial reperfusion the mean arterial pressure (MAPart) was significantly higher in DCD recipients (76mmHg vs. 69 mmHg, p=0.029). At the end of the transplants the pH was even better in those transplanted with DCD grafts (7.36 vs. 7.31, p=0.026) with a similar amount of bicarbonates infused. The postoperative outcome was similar at 3 and 12 months. Surprisingly the haemodynamic profile of recipients of DCD liver grafts is not significantly worse compared with DBD recipients possibly due to strict selection of grafts and recipients. Larger sample is needed to validate if higher MELD recipients could withstand the post reperfusion phase with DCD grafts