Background and objectives: Cardiovascular disease is highly prevalent in chronic kidney disease. Traditional risk factors are insufficient to explain the high cardiovascular disease prevalence. Free p-cresol serum concentrations, mainly circulating as its derivative p-cresyl sulfate, are associated with cardiovascular disease in hemodialysis patients. It is not known if p-cresol is associated with cardiovascular disease in patients with chronic kidney disease not yet on dialysis.Design, setting, participants, & measurements: In a prospective observational study in 499 patients with mild-to-moderate kidney disease, we examined the multivariate association between p-cresol free serum concentrations and cardiovascular events.Results: After a mean follow-up of 33 mo, 62 patients reached the primary end point of fatal or nonfatal cardiovascular events. Higher baseline concentrations of free p-cresol were directly associated with cardiovascular events (univariate hazard ratio [HR] 1.79, P < 0.0001). In multivariate analysis, p-cresol remained a predictor of cardiovascular events, independent of GFR and independent of Framingham risk factors (full model, HR 1.39, P ‫؍‬ 0.04).Conclusions: These findings suggest that p-cresol measurements may help to predict cardiovascular disease risk in renal patients over a wide range of residual renal function, beyond traditional markers of glomerular filtration. Whether p-cresol is a modifiable cardiovascular risk factor in CKD patients remains to be proven.

In this cohort of patients with CKD, we found that patients with aortic calcifications (ACs) had higher sclerostin levels. However, in multivariate analysis, the association became inverse. Additional clinical and experimental studies are urgently required to clarify whether or not sclerostin protects against progression of vascular calcification.

Background Preliminary evidence suggests that hemodialysis patients have a blunted early serological response to SARS-CoV-2 vaccination. Optimizing vaccination strategy in this population requires a thorough understanding of predictors and dynamics of humoral and cellular immune responses to different SARS-CoV2 vaccines. Methods This prospective multicenter study of 543 hemodialysis patients and 75 healthy volunteers evaluated the immune responses at 4 or 5 weeks and 8 or 9 weeks after administration of the BNT162b2 or mRNA-1273 vaccine, respectively. We assessed anti-SARS-CoV-2 spike antibodies and T cell responses by IFN-γ of peripheral blood lymphocytes upon SARS-CoV-2 glycoprotein stimulation (QuantiFERON assay) and evaluated potential predictors of the responses. Results Compared with healthy volunteers, hemodialysis patients had an incomplete, delayed humoral immune response and a blunted cellular immune response. Geometric mean antibody titers at both time points were significantly greater in patients vaccinated with mRNA-1273 versus BNT162b2, and a larger proportion of them achieved the threshold of 4160 AU/ml, corresponding with high neutralizing antibody titers in vitro (53.6% versus 31.8% at 8 or 9 weeks, P<0.0001). Patients vaccinated with mRNA-1273 versus BNT162b2 exhibited significantly greater median QuantiFERON responses at both time points, and a larger proportion achieved the threshold of 0.15 IU/ml (64.4% versus 46.9% at 8 or 9 weeks, P<0.0001). Multivariate analysis identified COVID-19 experience, vaccine type, use of immunosuppressive drugs, serum albumin, lymphocyte count, hepatitis B vaccine nonresponder status, and dialysis vintage as independent predictors of the humoral and cellular responses. Conclusions The mRNA-1273 vaccine's greater immunogenicity may be related to its higher mRNA dose. This suggests that a high-dose vaccine might improve the impaired immune response to SARS-CoV-2 vaccination in hemodialysis patients.