BACKGROUND AND AIMS The COVID-19 pandemic continues to be a worldwide health issue. Among haemodialysis (HD) patients, many countries opted for a three-dose immunization scheme with mRNA vaccines, as some patients did not produce a sufficient humoral response after the second one, and most developed a rapid decline in antibody levels over the months following vaccination. METHOD This observational, prospective, multi-centre study evaluated the humoral response, clinical outcomes (breakthrough infections, hospital admissions, severe COVID-19 and mortality), and their potential associated factors by determining the presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) before and after each of the three doses of SARS-CoV-2 mRNA vaccines with either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer) in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). RESULTS Unlike the general population, where most individuals seroconverted after one dose, HD patients required two doses to produce a positive anti-S1-RBD IgG response in most of them. Moreover, their antibody levels waned significantly three and 6 months after vaccination (see Figure 1). The decline in antibody levels was accompanied by seroreversion in 32% of patients. Notably, despite the precipitous drop, there was a low incidence of breakthrough infections (5.9%), with only one case of severe COVID-19 that required ICU admission and no deaths up until receiving the third vaccine dose. The administration of the third dose achieved seroconversion in 3 out of 4 non- or weak responders to two doses. Active cancer and immunosuppressive treatment were related to a worse humoral response. CONCLUSION Every haemodialysis patient should receive a third-dose vaccination scheme, with a booster dose three or 6 months after receiving the second one. Despite the lack of data, immunosuppressed and active cancer patients may benefit from more frequent vaccine boosters. Further monitoring of antibody levels will be needed to assess the maintenance of the humoral response in these patients.

BACKGROUND AND AIMS Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and these associated lipid disorders, in turn, contribute to the progression of CKD and its cardiovascular complications. Patients on peritoneal dialysis have a more atherogenic lipid profile than non-dialysis-dependent CKD patients or on HD. In the general population, the reduction of total cholesterol and LDL levels is associated with improved clinical outcomes in terms of morbidity and mortality; however, several studies have failed to obtain these same results in patients on dialysis. The use of lipidomics to detect a broader panel of lipid species can improve the prediction of the different alterations that influence cardiovascular mortality. METHOD This is a single-center prospective observational study of a cohort of CKD patients who start renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD). Data from 39 patients were examined. All samples for routine laboratories and lipidomics studies were obtained the day before starting CAPD (T0) and 6 months after (T1). Samples were analysed on an Ultra-Performance Liquid Chromatography system. The differences in the lipid profile analytical variables between baseline and 6 months after the start of CAPD were analysed. For the lipidomic analysis, each compound was grouped with its possible adducts and compound class based on the International Lipid Classification. RESULTS Thirty-nine patients were enrolled the study. Their mean age was 57.9 ± 16.3 years. The underlying renal diseases were glomerular disease (15 patients), diabetic kidney disease (10), congenital kidney disease (4), hypertensive kidney disease (2), interstitial nephropathy (2) and others (6). Hypertension was present in 96.3% of the patients, diabetes mellitus in 30.8% and 30 of the 39 patients had dyslipidemia (76.9%). Of the group of patients with dyslipidemia, only one of them was not on statin treatment. Table 1 shows the results of the analytical variables of lipid profile, serum glucose and renal function before and 6 months after initiating CAPD. The levels of CT and LDL were lower 6 months after CAPD initiation, but these were not statistically significant. Using the plasma lipid profile, with a mass spectrometry approach, a significant increase (P < 0.05) in total free fatty acids (FFA) was observed from T0 to T1. FFA (16:1) and FFA (18:0) were the FFAs with the highest peak response (Fig. 1). CONCLUSION Our LC-QTOF/MS-based lipidomics approach to study the effect of starting renal replacement therapy with CAPD in patients with CKD shows that total FFAs increased after 6 months on this technique. Within this group of lipids, FA 16:1 (palmitoleic acid) and FA 18:0 (stearic acid) were the ones that increased the most. An earlier study demonstrated that FFA levels are increased in the plasma of CKD patients; moreover, they have reported that higher levels of saturated fatty acids in serum correlate with sudden cardiac death in patients starting HD. Likewise, monounsaturated fatty acids are the products of stearoyl-CoA desaturase (SCD) catalyzed reactions and act as substrates to synthesize phospholipids and triglycerides. The activity of SCD is very high in patients with cardiovascular disease, hypertension and diabetes.

Background and Aims Early graft failure (EGL) is a devastating complication of kidney transplantation. Patients with EGL have an increased risk of mortality of up to twelve times compared to patients who received grafts that survive beyond 30 days. Moreover, they may have become sensitized to antigens from the failed graft and that human leukocyte antigen antibodies (anti-HLA), identified on single antigen bead assays, may not be reliable until several weeks after transplantation. Thus, if rapid re-transplantation occurs, there is no certainty regarding the recipient's immunological status. Hence, there could be an increased immunological risk with the consequent disturbance of the new graft's survival. Method We performed a retrospective single-center observational study in re-transplanted patients with EGL (defined as graft loss before 30 days from transplant) between January 1977 and November 2019 from our center to analyze the outcomes of rapid re-transplantation (occurred within 30 days of EGL) vs late re-transplantation (occurred beyond those 30 days). Results: T here were 82 re-transplants after EGL. The median overall patient survival after re-transplantation was 32 years. Eight patients died within the first year. Among the mortality causes, there were four septic shocks, one cardiogenic shock, one massive pulmonary thromboembolism, one myocardial infarction, and one unknown cause. When analyzed for periods, death censored graft survival was 89% at one and five years after re-transplantation. One graft was lost at eight days due to antibody-mediated rejection (AMR), while there was one death with a functioning graft three months after re-transplantation secondary to a pulmonary embolism. Seventy-three late re-transplants occurred. When analyzed for periods, death censored graft survival was 81% and 69% at one and five years after re-transplantation, respectively. The median patient survival after late re-transplantation was 32 years. There were fewer deaths after rapid re-transplantation than late re-transplantation, but given the small number of cases in the former, this difference did not reach statistical significance (p = 0.3). There was no association between the timing of re-transplantation and an increased risk of graft failure (HR 0.30 [0.04 – 2.2]). While four rapid re-transplants did not share any incompatibilities between donors, four did share at least one HLA type I incompatibility, and one shared an incompatibility of HLA class I and class II. There were no T-cell mediated rejections (TCMR), and there was only one AMR in the rapid rapid re-transplantation group, whereas there were six TCMRs and fifteen AMRs in the late re-transplantation group (p = 0.03 and p = 0.4, respectively). Conclusion Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor it diminishes long-term graft survival when compared to late re-transplantation.

BACKGROUND AND AIMS Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side-effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. METHOD This is an observational prospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose and reported symptoms were collected from October 2018 to March 2021. RESULTS Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%) and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). CONCLUSION We present the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population.