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

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

Nutritional Approaches for the Management of Metabolic Acidosis in Chronic Kidney Disease

Metabolic acidosis is a severe complication of chronic kidney disease (CKD) which is associated with nefarious impairments such as bone demineralization, muscle wasting, and hormonal alterations, for example, insulin resistance. Whilst it is possible to control this condition with alkali treatment, consisting in the oral administration of sodium citrate or sodium bicarbonate, this type of intervention is not free from side effects. On the contrary, opting for the implementation of a targeted dietetic-nutritional treatment for the control of CKD metabolic acidosis also comes with a range of additional benefits such as lipid profile control, increased vitamins, and antioxidants intake. In our review, we evaluated the main dietary-nutritional regimens useful to counteract metabolic acidosis, such as the Mediterranean diet, the alkaline diet, the low-protein diet, and the vegan low-protein diet, analyzing the potentialities and limits of every dietary-nutritional treatment. Literature data suggest that the Mediterranean and alkaline diets represent a valid nutritional approach in the prevention and correction of metabolic acidosis in CKD early stages, while the low-protein diet and the vegan low-protein diet are more effective in CKD advanced stages. In conclusion, we propose that tailored nutritional approaches should represent a valid therapeutic alternative to counteract metabolic acidosis

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

Aim: to assess the incidence and classification of acute kidney injury (AKI) after liver transplantation (LT). Methods: this is a retrospective single-centre study of 1151 patients who underwent LT at the University Hospital Birmingham from 2007 to 2014. Exclusion criteria included: urgent (=66) and living donor (=7) transplantation. We considered: renal function pre-transplant and daily within one week post-transplant, characteristics of recipient, donor type (DCD vs.DBD), graft variables and indicators of initial graft function. AKI was 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 significantly higher median MELD score (16.84 vs. 15.83, p=0.002) and serum bilirubin level (3.16 vs. 2.37, p<0.001) than DCD, whereas there were no differences in INR and serum creatinine values. Furthermore, DBD had significant 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 patients), of which 57.1% of DBD (474/830) vs. 60.5% of DCD (150/248). AKI classification is reported in the table. Conclusion: We demonstrate a higher incidence of post-LT stage 3 AKI in DCD, despite a better pre-LT liver function due to patient selection, compared to DBD. Compared to previous studies we note 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