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Introduction and Objectives: Since MELD implementation renal impairment in liver transplant (LT) recipients has become of increasing importance. This is the first study evaluating the course of renal function immediately prior to LT as predictor for long-term renal and overall outcome., Patients and Methods: In this retrospective study, 226 adults undergoing LT at the University Medical Center Hamburg-Eppendorf (2011-2015) were included. The impact of renal function over a period of 3 months prior to LT compared to renal function at the day of LT on long-term renal outcome and survival was assessed., Results: According to GFR at day of LT renal function improved (≥1 CKD stage) in 64 patients (28%), remained stable in 144 (64%) or deteriorated in 18 (8%). Improvement of renal function prior to LT did neither significantly affect 90-day (13% vs. 14%, p = 0.83), nor 5-year post-LT mortality (35% vs. 41%, p = 0.57). 50 patients (22%) with hepatorenal syndrome (HRS) received terlipressin prior to LT, but only 18 (37%) showed prolonged stabilization of renal function (improvement ≥1 CKD stage). Response to terlipressin did neither improve 90-day (p=1), 5-year mortality (p = 0.52) nor long-term renal function (p = 0.843). Nevertheless, need for dialysis pre-LT (59% vs. 34%, p = 0.005) and post-LT (62% vs. 17%, p<0.001) was associated with increased 5-year mortality., Conclusions: Improvement of renal function immediately prior to LT, either spontaneously or following terlipressin therapy, did neither ameliorate long-term renal outcome nor survival in LT recipients. Future studies need to clarify the impact of terlipressin in HRS on the transplant waiting time in LT candidates., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Patients with end-stage liver disease (ESLD) who develop hepatorenal syndrome (HRS) have very high mortality rates. For patients with HRS type I, median survival without specific therapy is only 2 weeks. Due to worsening clinical condition in such patients secondary to uremia and hepatic disease, some form of renal replacement therapy (RRT), either intermittent hemodialysis IHD or continuous veno-venous hemodialysis (CVVHD), must be instituted. However, the literature regarding the survival benefits of the hemodialysis for the worsening renal failure in liver cirrhotic patients remains limited. In this review, we performed a meta-analysis of nine different studies done in the last 2 decades that included 464 patients with end-stage liver disease with renal failure who received either pretransplantation or post-transplantation CVVHD. Survival of the patients was then analyzed with respect to patients with end-stage liver disease without renal failure that underwent liver transplantation (LT). Outcomes for the patients with pre-LT CVVHD were comparable with those of liver transplant recipients without renal failure. However, patients requiring post-LT hemodialysis for prolonged periods showed poor outcomes and a tendency to progress to chronic kidney disease. In all selected studies, patients with post-transplantation CVVHD for a prolonged period had a 3-year survival rate of ≤40%. This review highlights the role of pretransplantation CVVHD in selected patients with HRS who could achieve significantly better survival rates compared with patients without any renal replacement therapy or patients with post-transplantation CVVHD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Type 2 hepatorenal syndrome (HRS2) is a functional renal impairment complicating end-stage liver disease. Although it is reversible after liver transplantation, long-term posttransplant outcomes in HRS2 patients remain ill-defined., Methods: Retrospective, matched case-control (1:2) study of all adult HRS2 patients transplanted in our institution between 2000 and 2012. The HRS2 patients were identified from our electronic transplant database, and matched with controls for the following variables: age, sex, etiology, diabetes mellitus, and year of transplant., Results: Forty-two HRS2 patients were compared to 83 controls. At the time of transplant, HRS2 patients had an estimated glomerular filtration rate of 41 ± 1 mL/min per 1.73 m. The HRS2 patients had greater intraoperative packed red blood cell transfusion (P = 0.002), and longer intensive care unit (P = 0.01) as well as total hospital length of stay (P = 0.03). Reversal of HRS2 occurred in 88.1% patients, 5.7 ± 0.5 days after transplantation. Although HRS2 patients had lower initial exposure to calcineurin inhibitors, a greater proportion of HRS2 patients had chronic kidney disease stage 3 (CKD3) at 3 (53.8% vs 28.4%; P = 0.007) and 12 months (59.5% vs 38.2%; P = 0.03) compared to controls. One-year survival was similar between the 2 groups (log-rank P = 0.82). On multivariate analysis, pretransplant HRS2 was associated with CKD3 at 3 (odds ratio, 3.73; 95% confidence interval, 1.54-9.03; P = 0.004) and 12 months (odds ratio, 3.23; 95% confidence interval, 1.37-7.64; P = 0.007) after transplantation., Conclusions: Liver transplantation reverses HRS2 in the majority of patients with survival outcomes comparable to matched controls, despite longer stays in intensive care unit and in hospital. Pretransplant HRS2 is associated with early posttransplant CKD3, despite calcineurin-inhibitor minimization.

Unlabelled: Type-1 hepatorenal syndrome (HRS) is a common complication of bacterial infections in cirrhosis, but its natural history remains undefined. To assess the outcome of kidney function and survival of patients with type-1 HRS associated with infections, 70 patients diagnosed during a 6-year period were evaluated prospectively. Main outcomes were no reversibility of type-1 HRS during treatment of the infection and 3-month survival. Forty-seven (67%) of the 70 patients had no reversibility of type-1 HRS during treatment of the infection. [Correction to previous sentence added March 10, 2014, after first online publication: "Twenty-three (33%)" was changed to "Forty-seven (67%)."] The main predictive factor of no reversibility of type-1 HRS was absence of infection resolution (no reversibility: 96% versus 48% in patients without and with resolution of the infection; P < 0.001). Independent predictive factors of no reversibility of type-1 HRS were age, high baseline serum bilirubin, nosocomial infection, and reduction in serum creatinine <0.3 mg/dL at day 3 of antibiotic treatment. No reversibility was also associated with severity of circulatory dysfunction, as indicated by more marked activity of the vasoconstrictor systems. In the whole series, 3-month probability of survival was only 21%. Factors associated with poor prognosis were baseline serum bilirubin, no reversibility of type-1 HRS, lack of resolution of the infection, and development of septic shock after diagnosis of type-1 HRS., Conclusion: Type-1 HRS associated with infections is not reversible in two-thirds of patients with treatment of infection only. No reversibility of type-1 HRS is associated with lack of resolution of the infection, age, high bilirubin, and no early improvement of kidney function and implies a poor prognosis. These results may help advance the management of patients with type-1 HRS associated with infections., (© 2014 by the American Association for the Study of Liver Diseases.)

Background and Objectives: Candidates with AKI including hepatorenal syndrome often recover renal function after successful liver transplantation (LT). This study examined the incidence and risk factors associated with renal nonrecovery within 6 months of LT alone among those receiving acute renal replacement therapy (RRT) before LT., Design, Setting, Participants, & Measurements: Scientific Registry of Transplant Recipients data were linked with Centers for Medicare and Medicaid Services ESRD data for 2112 adult deceased-donor LT-alone recipients who received acute RRT for ≤90 days before LT (February 28, 2002 to August 31, 2010). Primary outcome was renal nonrecovery (post-LT ESRD), defined as transition to chronic dialysis or waitlisting or receipt of kidney transplant within 6 months of LT. Cumulative incidence of renal nonrecovery was calculated using competing risk analysis. Cox regression identified recipient and donor predictors of renal nonrecovery., Results: The cumulative incidence of renal nonrecovery after LT alone among those receiving the pre-LT acute RRT was 8.9%. Adjusted renal nonrecovery risk increased by 3.6% per day of pre-LT RRT (P<0.001). Age at LT per 5 years (P=0.02), previous-LT (P=0.01), and pre-LT diabetes (P<0.001) were significant risk factors of renal nonrecovery. Twenty-one percent of recipients died within 6 months of LT. Duration of pretransplant RRT did not predict 6-month post-transplant mortality., Conclusions: Among recipients on acute RRT before LT who survived after LT alone, the majority recovered their renal function within 6 months of LT. Longer pre-LT RRT duration, advanced age, diabetes, and re-LT were significantly associated with increased risk of renal nonrecovery.

Cholemic nephrosis represents a spectrum of renal injury from proximal tubulopathy to intrarenal bile cast formation found in patients with severe liver dysfunction. However, the contribution of this diagnosis has been largely forgotten in the modern literature. To more precisely define this, we conducted a clinicopathologic study of 44 subjects (41 autopsies and 3 renal biopsies) from jaundiced patients at the University of Chicago. Of these, 24 patients had bile casts with involvement of distal nephron segments in 18 mild cases and extension to proximal tubules for 6 severe cases. Eleven of 13 patients with hepatorenal syndrome and all 10 with cirrhosis (due to alcoholism) had tubular bile casts. These casts significantly correlated with higher serum total and direct bilirubin levels, and a trend toward higher serum creatinine, AST, and ALT levels. Bile casts may contribute to the kidney injury of severely jaundiced patients by direct bile and bilirubin toxicity, and tubular obstruction. Both mechanisms are analogous to the injury by myeloma or myoglobin casts. Accounting for the presence of renal bile casts provides a more complete representation of the renal injury that can occur in this unique clinical setting. Thus, bile cast nephropathy is an appropriate term for the severe form of injury observed in the spectrum of cholemic nephrosis. Additional studies are needed to establish the significance of this parameter for patient management in different clinical settings.

Background: The combination of octreotide, midodrine, and albumin (triple therapy) is used to treat hepatorenal syndrome (HRS) often as a bridge to liver transplantation (LT). We examined post-LT outcomes in recipients with HRS, including the effect of pre-LT triple therapy., Methods: Patients with HRS treated with triple therapy (cases) pre-LT were compared with a cohort that underwent LT in the immediate era before triple therapy was used (controls)., Results: Forty-three patients with HRS underwent LT (27 cases and 16 controls). Twenty-one patients (49%) required hemodialysis (HD) pre-LT (48% of cases vs. 50% of controls, P=1.00). After LT, mean glomerular filtration rate (GFR) was similar between cases and controls at 1 month (56.9 vs. 52.6 mL/min/1.73 m(2), P=0.61) and at 1 year (P=0.13). Of the 27 cases, 11 responded to triple therapy pre-LT. Compared with nonresponders, there was no difference in GFR at 1 month (57.2 vs. 56.6 mL/min/1.73 m, P=0.96) or 1 year (P=0.48) post-LT. Long-term HD after LT was required in 7.7% of cases and 12.5% of controls (P=0.61)., Conclusions: LT alone improved renal function in most patients with HRS, including those requiring short-term HD. Pre-LT treatment of HRS with triple therapy was not associated with additional benefit in GFR after LT.

Background: Studies suggest that terlipressin is effective in the treatment of hepatorenal syndrome (HRS). However, factors predicting response to therapy and the long-term outcome of patients have not been defined., Methods: We reviewed all patients from our institution treated with terlipressin between July 1, 2001 and December 31, 2005 for HRS. Follow up continued until June 30, 2006. HRS was defined according to the International Ascites Club. The following data were retrieved: age, gender, etiology of liver disease, Child-Pugh score, HRS precipitant, therapy duration, creatinine at day 0 and end of treatment, adverse events, and patient outcome., Results: Sixty-nine patients were included. Forty-nine episodes (71%) of HRS were type 1, and 20 episodes (29%) type 2. Forty-one (59.4%) patients responded to terlipressin. Two variables predicted renal function improvement: type 1 HRS and age. Twenty-one (30.4%) patients survived; 17 (81%) had type 1 HRS while four (19%) had type 2 HRS (P = 0.27). The only factor predicting transplant-free survival was type 1 HRS. No patients with type 2 HRS survived without transplantation (P = 0.02)., Conclusions: The only factor predicting transplant-free survival following terlipressin therapy is the presence of type 1 HRS. Therefore, it is difficult to justify the use of this drug in patients with type 2 HRS who are not liver transplant candidates.