Efficacy and Safety of COVID-19 Vaccine in Patients on Renal Replacement Therapy.

Patients with CKD on RRT are at high risk for severe disease and mortality in COVID-19 disease. We decided to conduct an observational prospective study to evaluate antibody response after vaccination for COVID-19 in a cohort of 210 adult patients on RRT (148 on HD; 20 on PD; and 42 kidney transplant recipients). Blood samples were taken before and 4 weeks after vaccination. Antibody levels were evaluated with CLIA immunoassay testing for IgG anti-trimeric spike protein of SARS-CoV-2. A positive antibody titer was present in 89.9% of HD patients, 90% of PD patients, and 52.4% of kidney transplant recipients. Non-responders were more frequent among patients on immunosuppressive therapy. Mycophenolate use in kidney transplant patients was associated with lower antibody response. The median antibody titer was 626 (228-1480) BAU/mL; higher in younger patients and those previously exposed to the virus and lower in HD patients with neoplasms and/or on immunosuppressive therapy. Only two patients developed COVID-19 in the observation period: they both had mild disease and antibody titers lower than 1000 BAU/mL. Our data show a valid response to COVID-19 mRNA vaccination in HD and PD patients and a reduced response in kidney transplant recipients. Mycophenolate was the most relevant factor associated with low response.

Effects of a medium cut-off (Theranova®) dialyser on haemodialysis patients: a prospective, cross-over study.

BACKGROUND: Despite significant advances in haemodialysis (HD) in recent decades, current dialysis techniques are limited by inadequate removal of uraemic solutes such as middle molecules and protein-bound uraemic toxins. Novel medium cut-off (MCO) membrane or 'expanded haemodialysis' (HDx) provides diffusive removal of conventional and large middle molecular weight uraemic toxins, with marginal albumin leak. METHODS: This prospective, open-label, controlled, cross-over pilot study compared HDx (novel MCO membrane Theranova® 400) and conventional HD in 20 prevalent HD patients. Biochemical, dialysis adequacy and safety measures (adverse events, infections and hospitalization frequency) were recorded. Ten patients underwent conventional HD high-flux dialyser and 10 patients underwent HDx for 3 months, and the patients then switched and received the other treatment for a further 3 months. RESULTS: Treatment with HDx was associated with a significant reduction in serum albumin concentration [median (interquartile range) reduction -0.45 g/dL (-0.575 to -0.05); P = 0.025]. However, median albumin levels were ≥3.5 g/dL and no patients had clinical symptoms of hypoalbuminaemia or needed intravenous albumin administration. The number of infections was lower in patients treated with HDx (n = 7/19) compared with patients treated with HD (n = 14/20; P = 0.03). Patients treated with HDx had reduced levels of interleukin (IL)-1ß (from 0.06 ± 0.02 pg/mL versus 0.28 ± 0.18 pg/mL with HD) and IL-6 (6.45 ± 1.57 pg/mL versus 9.48 ± 2.15 pg/mL), while tumour necrosis factor-α levels remain unchanged. CONCLUSIONS: This study demonstrates that the chronic use of the novel MCO dialyser Theranova® appears to be safe and well-tolerated, without serious side effects or hypoalbuminaemia, as well as fewer infections. These results need to be confirmed in larger randomized clinical trials.

Real-world data on healthcare resource consumption and costs before and after kidney transplantation.

End-stage renal disease (ESRD) is increasing worldwide as a consequence of population aging and increasing chronic illness. Treatment consists mostly of dialysis and kidney transplantation (KTx), and KTx offers advantages for life expectancy and long-term cost reductions compared with dialysis. This study uses the administrative database of the Lombardy Region to analyze the costs of a cohort of patients with ESRD receiving KTx, covering a time period of 24 months before transplant to 12 months after. During 2011, 276 patients underwent kidney transplantation (8.7% preemptive and 91.3% non-preemptive). In the period before transplantation, the main cost driver was dialysis (66.6% for the period from -24 to -12 months and 73.8% for the period from -12 to 0 months), while in the 12 months after KTx, the most relevant cost was surgery. The total cost -24 to -12 months pre-KTx was 35 049.2€; the cost -12 to 0 months was 36 745.9€; and the cost 12 months after KTx was 43 805.8€. Non-preemptive patients showed much higher costs both pre- and post-KTx than preemptive patients. This study highlights how KTx modifies the resource consumption and costs composition of patients with ESRD vs those undergoing dialysis treatment and how KTx may be economically beneficial, especially preemptive intervention.

Efficacy and safety of once-monthly continuous erythropoietin receptor activator in patients with chronic renal anemia.

BACKGROUND: In the management of anemia in patients with chronic kidney disease stage 5 undergoing dialysis (CKD-5D), maintaining hemoglobin (Hb) within the range recommended by the guidelines is challenging. METHODS: The CARISMA study aim was to evaluate the efficacy, safety and tolerability of a once-monthly continuous erythropoietin receptor activator (CERA) for the treatment of anemia in CKD-5D patients. In this single-arm, multicenter, open-label, phase IIIb study, we screened adult patients from 66 centers in Italy receiving intravenous epoetin alfa or beta or darbepoetin alfa. Eligible patients entered the CERA dose titration phase (DTP), followed by an efficacy evaluation period (EEP) and a long-term safety period (LTSP). Patients were analyzed by intention-to-treat (ITT), per protocol (PP) and safety populations. RESULTS: The rate of patients maintaining Hb within the range 10.0-12.0 g/dL throughout the EEP was 63.22% (220/348), and concentration from baseline to any postbaseline time point. CERA may thus offer a convenient and effective treatment 73.94% (122/165) in the ITT and PP population, respectively, periods in both populations. The rate of patients requiring a dose change was higher during the DTP (69.2%) and the LTSP (73.0%) than during the EEP (54.5%), as expected. CERA treatment was generally well tolerated. CONCLUSIONS: Once-monthly CERA administered to CKD-5D patients was associated with negligible changes in mean Hb option for these patients.

Confounding effect of comorbidity in survival studies in patients on renal replacement therapy.

BACKGROUND: After taking other confounding factors into account, the impact of comorbidity on mortality was investigated when comparing mortality between five European countries, dialysis modalities and renal disease groups. METHODS: The study included 15 571 incident patients on renal replacement therapy (RRT) from five national or regional registries participating in the European Renal Association-European Dialysis and Transplant Association Registry that collect comorbidity data. The presence of diabetes mellitus, ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and malignancy was recorded at the start of RRT. RESULTS: The comorbidities were each independently associated with mortality, with hazard ratios (HRs) ranging from 1.40 (95% CI: 1.30-1.51) for peripheral vascular disease to 1.65 (95% CI: 1.48-1.83) for diabetes. Age, gender, primary renal disease, modality and country together explained 14.4% of the variance in mortality; the comorbidities explained an additional 1.9%. In the comparison of renal vascular disease with glomerulonephritis, the crude HR of 2.40 (95% CI: 2.12-2.72) changed to 1.24 (95% CI: 1.09-1.41) after adjustment for age, gender, primary renal disease, treatment modality and country and to 1.06 (95% CI: 0.93-1.22) after further adjustment for the comorbidities. For the comparison between countries and other patient groups, the change in the survival estimate after adjustment for comorbidity was less. CONCLUSION: Comorbidity is an important predictor for mortality. However, after adjustment for age, gender, primary renal disease, treatment modality and country, when comparing outcomes between patient groups the influence of comorbidity may be less important than expected.

Prevalence of co-morbidity in different European RRT populations and its effect on access to renal transplantation.

BACKGROUND: This study compared the prevalence of co-morbidity in patients starting renal replacement therapy (RRT) between European countries and further examined how co-morbidity affects access to transplantation. METHODS: In this ERA-EDTA registry special study, 17907 patients from Austria, Catalonia (Spain), Lombardy (Italy), Norway, and the UK (England/Wales) were included (1994-2001). Co-morbidity was recorded at the start of RRT. RESULTS: The prevalence of co-morbidity was: diabetes mellitus (DM) (primary renal disease and co-morbidity) 28%, ischaemic heart disease (IHD) 23%, peripheral vascular disease (PVD) 24%, cerebrovascular disease (CVD) 14% and malignancy 11%. With exception of malignancy, the prevalence of co-morbidity was highest in Austria, but differences were small among other countries. With exception of DM, males suffered more often from co-morbidity than females. In general, the percentage of haemodialysis was higher in patients with co-morbidity, but treatment modality differed substantially between countries. Using a Cox regression with adjustment for demographics, country, year of start and other co-morbidities, the presence of each of the co-morbid conditions made it less likely [RR; 95%CI] to receive a transplant within 4 years: DM [0.79; 0.70-0.88], IHD [0.59; 0.50-0.70], PVD [0.57; 0.49-0.67], CVD [0.49; 0.39-0.61], and malignancy [0.32; 0.24-0.42]. The age, gender and year of start adjusted relative risk [95%CI] to receive a renal transplant within 4 years ranged from 0.23 [0.19-0.27] for Lombardy (Italy) to 3.86 [3.36-4.45] for Norway (Austria = reference). These international differences existed for patients with and without co-morbidity. CONCLUSIONS: The prevalence of co-morbidity was highest in Austria but differences were small among other countries. The access to a renal graft was most affected by the presence of malignancy and least affected by the presence of DM. International differences in access to transplantation were only partly due to co-morbid variability.