The advances in transplant immunosuppression have reduced substantially the incidence of kidney graft rejection. In recent years, the focus has moved from preventing rejection to preventing the long-term consequences of long-standing immunosuppression, including nephrotoxicity induced by calcineurin inhibitors (CNI), as well as infectious and neoplastic complications. Since the appearance in the late 1990s of mTOR inhibitors (mTORi), these unmet needs in immunosuppression management could be addressed thanks to their benefits (reduced rate of viral infections and cancer). However, management of side effects can be troublesome and hands-on experience is needed. Here, we review all the available information about them. Thanks to all the basic, translational and clinical research achieved in the last twenty years, we now use mTORi as de novo immunosuppression in association with CNI. Another possibility is represented by the conversion of either CNI or mycophenolate (MPA) to an mTORi later on after transplantation in low-risk kidney transplant recipients.

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases; however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non- or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters.

Background: High-volume online hemodiafiltration (OL-HDF) has proven to be the most efficient dialysis modality and to offer better clinical outcomes in patients on hemodialysis. Longer and more frequent dialysis sessions have demonstrated clinical and survival benefits. Methods: A single-center observational study of the first one hundred patients on nocturnal every-other-day OL-HDF was conducted with the aim of reporting the experience with this treatment schedule and evaluating analytical and clinical outcomes as well as the patient and technique survival. Results: Nocturnal OL-HDF on alternate days was highly accepted, with no adverse symptoms, good clinical tolerance, and maintained active work in 62%. Kt, and the convective volume increased from 67.6 ± 12 L to 105.4 ± 11.7 L, and from 27.1 ± 4.6 L to 48.1 ± 6.4 L, respectively, from the baseline to 24 months. An improved calcium–phosphate balance and blood pressure control were observed, as the use of phosphate binders and antihypertensive medications decreased from 76.7% to 3.3% and from 56.7% to 28.3%, respectively. Furthermore, 58.3% of patients required phosphate supplementation in the dialysis fluid to prevent intradialytic hypophosphatemia. Additionally, doses of iron and erythropoiesis-stimulating agents were reduced. The global patient survival was 94% at the end of the follow-up. It was higher in those on the transplant waiting list, with 98.1% survival compared to 84.6% in non-wait-listed patients at 24 months. The main reason for treatment discontinuation was kidney transplantation, accounting for 78.4% of the 88 withdrawals, while death was the leading cause of discontinuation in non-listed patients (41.6%). Conclusions: Nocturnal every-other-day OL-HDF is a well-tolerated dialysis regimen that offers significant clinical benefits, which may positively impact morbidity and mortality. Additionally, it allows patients to integrate the treatment into their social and occupational lives.

Acetate is widely used as a dialysate buffer to avoid the precipitation of bicarbonate salts. However, even at low concentrations that wouldn’t surpass the metabolic capacity of the Krebs tricarboxylic acid (TCA) cycle, other metabolic routes are activated, leading to undesirable clinical consequences by poorly understood mechanisms. This study aims to add information that could biologically explain the clinical improvements found in patients using citrate dialysate. A unicentric, cross-over, prospective targeted metabolomics study was designed to analyze the differences between two dialysates, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Fifteen metabolites were studied to investigate changes induced in the TCA cycle, glycolysis, anaerobic metabolism, ketone bodies, and triglyceride and aminoacidic metabolism. Twenty-one patients completed the study. Citrate increased during the dialysis sessions when CD was used, without surpassing normal values. Other differences found in the next TCA cycle steps showed an increased substrate accumulation when using AD. While lactate decreased, pyruvate remained stable, and ketogenesis was boosted during dialysis. Acetylcarnitine and myo-inositol were reduced during dialysis, while glycerol remained constant. Lastly, glutamate and glutarate decreased due to the inhibition of amino acidic degradation. This study raises new hypotheses that need further investigation to understand better the biochemical processes that dialysis and the different dialysate buffers induce in the patient’s metabolism.

Background. Frailty is highly prevalent among patients with heart failure (HF) and is associated with adverse clinical outcomes. Chronic kidney disease (CKD) frequently coexists with HF and may further increase risk. However, the clinical profile linking frailty and CKD remains insufficiently characterized. This study aimed to determine the prevalence and clinical correlates of frailty in outpatients with HF and to assess whether its prognostic significance varies across CKD severity. Methods. A prospective, observational cohort of HF outpatients was enrolled. Frailty was defined according to Fried’s phenotype (≥3 criteria). Factors associated with frailty were identified using logistic regression. The primary endpoint was a composite of all-cause mortality or HF hospitalization over one year. Cox proportional hazards models were used to evaluate associations between frailty and outcomes and to test its interaction with CKD. Results. A total of 459 HF outpatients (median age 75 [IQR 68–82] years; 72% men) were included. Frailty was present in 39.9% of patients and increased progressively with worsening renal function—from 14% in those with eGFR >60 to 38% in eGFR 30–60 and 48% in eGFR <30 mL/min/1.73 m² (p < 0.001). In multivariate analysis, older age, prior stroke, higher CA125 levels, and lower eGFR were independently associated with frailty. Frail patients had a higher risk of all-cause death or HF hospitalization (adjusted HR 2.09; 95% CI 1.22–3.58; p = 0.007), with an amplified effect among those with advanced CKD (HR 5.02; 95% CI 2.46–10.22; p < 0.001). Conclusions. In HF outpatients, frailty is common and closely linked to renal dysfunction. Its coexistence with advanced CKD identifies a subgroup at the highest risk of adverse outcomes. Combined assessment of frailty and renal function may enhance prognostic precision and guide more individualized therapeutic strategies.