Immune Response to Third and Fourth COVID-19 Vaccination in Hemodialysis Patients and Kidney Transplant Recipients.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a serious hazard for hemodialysis (HD) patients and kidney transplant (KTX) recipients as they suffer from an impaired immune response to SARS-CoV-2 vaccination. In addition, a definition of SARS-CoV-2 IgG titer that indicates a sufficient immune response, especially against new omicron variants, is urgently needed. In the present study, the immune response to either a third or a fourth dose of a mRNA vaccine was investigated in 309 dialysis and 36 KTX patients. SARS-CoV-2 IgG titer thresholds indicating neutralizing activity against wild type (WT) and the omicron variant BA.1 were quantified. After four vaccine doses, a high-neutralizing activity against WT was evidenced in HD patients, whereas the neutralizing rate against BA.1 was significant lower. Concerning KTX recipients, humoral and cellular immune responses after a third vaccination were still highly impaired. This calls for modified omicron-targeting vaccines.

Evaluation of a New Spike (S)-Protein-Based Commercial Immunoassay for the Detection of Anti-SARS-CoV-2 IgG.

Background: The investigation of the antibody response to SARS-CoV-2 represents a key aspect in facing the COVID-19 pandemic. In the present study, we compared the new Immundiagnostik IDK® anti-SARS-CoV-2 S1 IgG assay with four widely-used commercial serological assays for the detection of antibodies targeting S (spike) and NC (nucleocapsid) proteins. Methods: Serum samples were taken from an unbiased group of convalescent patients and from a negative control group. Sample were simultaneously analyzed by the new Immundiagnostik IDK® anti-SARS-CoV-2 S1 IgG assay, by the DiaSorin LIAISON® SARS-CoV-2 S1/S2 IgG assay, and by the Euroimmun anti-SARS-CoV-2 S1 IgG ELISA. Antibodies binding NC were detected by the Abbott SARS-CoV-2 IgG assay and by the pan-immunoglobulin immunoassay Roche Elecsys® anti-SARS-CoV-2. Moreover, we investigated samples of a group of COVID-19 convalescent subjects that were primarily tested S1 IgG non-reactive. Samples were also tested by live virus and pseudovirus neutralization tests. Results: Overall, the IDK® anti-SARS-CoV-2 S1 IgG assay showed the highest sensitivity among the evaluated spike (S) protein-based assays. Additionally, the Immundiagnostik assay correlated well with serum-neutralizing activity. Conclusions: The novel IDK® anti-SARS-CoV-2 S1 IgG assay showed high sensitivity and specificity, representing a valid option for use in the routine diagnostic.

Immune Responses to SARS-CoV-2 Infection and Vaccination in Dialysis Patients and Kidney Transplant Recipients.

Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status. The latter criterion included SARS-CoV-2-naïve patients with or without COVID-19 vaccination and convalescent patients receiving a booster shot. Serologies of 27 vaccinated healthy individuals served as the reference group. Vaccine-induced cellular immune response was quantified by an interferon-γ release assay in 32 KTX recipients. We determined seroconversion rates of 92.6%, 93.4%, and 71.4% in dialysis patients vaccinated with either BNT162b2, mRNA-1273, or AZD1222, respectively. Vaccination-induced anti-SARS-CoV-2 antibody titers were lower in dialysis patients compared to healthy individuals, and vaccination with mRNA-1273 induced higher titers than BNT162b2. The initial seroconversion rate was 39.5% in KTX recipients vaccinated with BNT162b2. A linear regression model identified medication with mycophenolate-mofetil/mycophenolic acid as an independent risk factor for missing seroconversion. Within a cohort of 32 KTX recipients, cellular and humoral immune reactivity to SARS-CoV-2 was detectable in three patients only. Conclusively, vaccine-induced seroconversion rates were similar in dialysis patients compared to healthy individuals but were strongly impaired in KTX recipients. Anti-SARS-CoV-2 IgG titers elicited by double active immunization were significantly lower in both cohorts compared to healthy individuals, and immune responses to vaccination vanished quickly.

Prospective evaluation of a clinical score for 60-day mortality after transjugular intrahepatic portosystemic stent-shunt: Bonn TIPSS early mortality analysis.

OBJECTIVE: Transjugular intrahepatic portosystemic stent-shunt (TIPSS) is increasingly used to treat complications of portal hypertension, but proven tools for risk assessment of early mortality are lacking. DESIGN: The prospective evaluation of a new 60-day mortality score. PATIENTS AND METHODS: In a tertiary medical centre, 30 consecutive TIPSS patients were analysed for early mortality predictors, such as Child-Pugh score, TIPSS urgency (elective: > or = 36 h or emergency: < 36 h after variceal bleeding), comorbidity (Acute Physiology and Chronic Health Evaluation [APACHE]-II) and clinical data. Main predictors (P< 0.01) in this group (group-1: Child-Pugh score 10A, 10B, 10C) were graded (1, 2 or 3 points representing low, medium and high risk, respectively) and summarized as a Bonn TIPSS early mortality (BOTEM) score. This score was then tested prospectively in the next 73 TIPSS patients (group-2: Child-Pugh score 14A, 42B, 17C). RESULTS: Group 1 early mortality (30%) depended primarily on bilirubin (P< 0.005), APACHE-II (P < 0.001) and TIPSS urgency (P< 0.001). Added risk points (1, 2, 3) for bilirubin (< 3 mg/dl, 3-6 mg/dl, > 6 mg/dl, respectively), APACHE-II (< 10, 10-20, > 20 points, respectively) and urgency (elective, emergency, active bleeding, respectively) represented individual BOTEM score points. BOTEM was the best mortality predictor (P< 0.001); < or = / > 6 score points was the optimal cut-off, with 56% sensitivity, 100% specificity, 100% positive predictive value, 84% negative predictive value and 87% accuracy. In group 2, early mortality (8.2%) was again best predicted by BOTEM (P < 0.01) with the same cut-off and 67% sensitivity, 99% specificity, 80% positive predictive value, 97% negative predictive value and 96% accuracy. CONCLUSION: BOTEM score based on bilirubin, comorbidity and TIPSS-urgency predicts rather reliably post-TIPSS 60-day mortality and might optimize TIPSS treatment.

Cholesterol metabolism in patients with chronic renal failure on hemodialysis.

Premature atherosclerosis is a major concern in patients on chronic dialysis and the identification of risk factors is important for preventive and interventional strategies. Other than the recognized atherogenic lipoprotein levels, little is known about overall cholesterol metabolism in patients on chronic hemodialysis (HD) and the best therapeutic intervention is still being debated. Therefore, we investigated intestinal cholesterol absorption, cholesterol and bile acid synthesis, and non-cholesterol plasma sterols in eight patients on dialysis and compared the results to those of 16 healthy male controls matched for body mass index and dietary cholesterol intake. Total, low-density lipoprotein (LDL) cholesterol, and triglycerides did not differ between the groups, but dialysis patients had a significantly lower high-density lipoprotein (HDL) cholesterol level (39 +/- 11 mg/dL vs. 48 +/- 10 mg/dL, p < 0.045). However, fractional cholesterol absorption, was significantly lower in dialysis patients (42.8 +/- 10.9% vs. 53.4 +/- 11%, p < 0.035), whereas plasma plant sterol concentrations and their ratios to cholesterol did not differ. Bile acid and total cholesterol synthesis were lower in dialysis patients (40% and -25%, respectively), although the differences were not significant. In contrast, lathosterol and its ratio to cholesterol in plasma was significantly lower in dialysis patients (0.176 +/- 0.084 mg/dL vs. 0.251 +/- 0.102 mg/dL, p < 0.024 and 0.733 +/- 0.353 microg/mg vs. 1.172 +/- 0.407 microg/mg, p < 0.017, respectively), indicating reduced hepatic de novo cholesterol synthesis. It is concluded that reduced HDL cholesterol and reduced bile acid synthesis contributes to atherosclerosis pathogenesis in dialysis patients, whereas intestinal cholesterol absorption and hepatic cholesterol synthesis did not seem dominant in this process at this stage of disease. Consequently, treatment with bile acid binding resins could be preferable to treatment with cholesterol absorption and synthesis inhibitors.

Degree of hepatic dysfunction and improvement of renal function predict survival in patients with HRS type I: a retrospective analysis.

BACKGROUND: Hepatorenal syndrome (HRS) is a frequent complication of end-stage liver cirrhosis. HRS type I has a very poor prognosis. From which of the more or less established therapies, such as use of vasoconstrictors together with albumin or placement of a Transjugular Intrahepatic Portosystemic Shunt patients might profit remains elusive. Therefore, it is important to define parameters that predict an improved outcome in respect to kidney function and survival. METHODS: The clinical charts of 91 patients with cirrhosis and HRS type I were studied. The parameters associated with response to therapy, defined as a decrease in serum creatinine of more than 1.5 mg/dl on day 14 after diagnosis of HRS, and those associated with survival were assessed by multivariate analysis. RESULTS: The median survival was 2.7 (1.5-3.8) months. Three independent predictive factors for survival were identified: Child-Pugh score (P = 0.05), Model of End-Stage Liver Disease (MELD) score less than 20 (P = 0.01), and response to therapy (P = 0.02). The Child-Pugh score (P = 0.00) and MELD score less than 20 (P = 0.02) were the parameters independently associated with the response to therapy, which occurred in 26% of the patients. CONCLUSION: Our data of this large monocentric series with HRS type I confirm the poor prognosis in these patients, especially in those with high Child-Pugh and MELD scores, and in those in whom kidney function does not improve within 2 weeks.

Comparison of MELD, Child-Pugh, and Emory model for the prediction of survival in patients undergoing transjugular intrahepatic portosystemic shunting.

OBJECTIVES: Recently, new prognostic models (Model for End-Stage Liver Disease [MELD model] and Emory score) were proposed for the prediction of survival in transjugular intrahepatic portosystemic shunt (TIPS) patients. Although the MELD model is considered to be superior and has consecutively been applied to priority listing for liver transplantation, these models have never been directly compared in terms of long-term prognosis. We therefore compared the prognostic accuracy of the different models, including the Child-Pugh score, in an unselected cohort of TIPS patients followed long-term. METHODS: Baseline risk scores for 162 unselected consecutive TIPS patients followed until death (n = 81), liver transplantation, or end of observation (n = 81) (mean follow-up 30.7 +/- 26.4 months) were calculated, and respective concordance- (c-)statistics for the predictive accuracy of 3-, 12-, and 36-month survival for the three models were compared statistically. RESULTS: All three models predicted short-term (3-month) survival with similar accuracy. The MELD model generated the best c-statistics for both 12-month (c-statistic 0.73, 95% CI = 0.64-0.82) and 36-month survival (c-statistic 0.74, 95% CI = 0.64-0.84). The predictive accuracy of the Emory score was significantly lower (c-statistic for 12-month survival: 0.60, 95% CI = 0.52-0.68, p = 0.012 vs MELD). In the statistical comparison of the MELD and the Child-Pugh model, only a trend favoring MELD for the prediction of 1-yr survival in patients with intestinal bleeding could be observed (MELD: c-statistic 0.78, 95% CI = 0.67-0.89; Child-Pugh: c-statistic 0.67, 95% CI = 0.55-0.80, p = 0.059). CONCLUSIONS: The MELD model is superior to the Emory score but only slightly superior to the Child-Pugh classification for the prediction of long-term survival in TIPS patients.

Prognostic impact of renal impairment and sodium imbalance in patients undergoing transjugular intrahepatic portosystemic shunting for the prevention of variceal rebleeding.

BACKGROUND/AIM: Kidney function and portal pressure have prognostic relevance in nonshunted patients with cirrhosis. Since insertion of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal pressure and may improve the renal function, the aim of the present study was to investigate the prognostic role of renal impairment and portal hemodynamics in patients with compensated cirrhosis electively shunted due to recurrent variceal hemorrhages. METHODS: Data of 101 consecutive and prospectively followed patients with compensated cirrhosis (bilirubin <5 mg/dl) undergoing elective TIPS due to recurrent variceal bleeding (45 died, and 8 were transplanted during the follow-up period) were evaluated in a multivariate Cox model. RESULTS: Creatinine and sodium were identified as the only independent predictors of survival in this model. The 90th percentile of creatinine (>1.7 mg/dl) defined a subgroup with a similar poor prognosis as the 90th percentile of the model for end-stage liver disease (MELD) score. Neither baseline nor post-TIPS portal pressure correlated with the long-term outcome. CONCLUSIONS: In compensated patients undergoing TIPS due to variceal bleeding, renal impairment indicates a poor prognosis. Portal hemodynamic parameters are not predictive of survival in TIPS patients.