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

The Role of Uremic Retention Solutes in the MIA Syndrome in Hemodialysis Subjects

International audienceIntroduction: In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the "MIA syndrome."Methods: In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients. Results: As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (r = 0.54 and 0.37, respectively; p < 0.05). Moreover, total cholesterol and phosphate directly correlate (r = 0.40, p < 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = -0.56, r = -0.39, respectively; p < 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (r = 0.81, r = 0.66, respectively; p < 0.01). Conclusion: We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the uremic milieu in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors

Chronic kidney disease: the missing concept in the 2019 EULAR/ERA-EDTA recommendations for lupus nephritis

Chronic kidney disease (CKD) is diagnosed when glomerular filtration rate (GFR) falls below 60 mL/min/1.73 m2 or urinary albumin: creatinine ratio (UACR) reaches ≥ 30 mg/g, as these two thresholds indicate a higher risk of adverse health outcomes, including cardiovascular mortality. CKD is classified into mild, moderate or severe, based on GFR and UACR values, and the latter two convey a high or very high cardiovascular risk, respectively. Additionally, CKD can be diagnosed based on abnormalities detected by histology or imaging. Lupus nephritis (LN) is a cause of CKD. Despite the high cardiovascular mortality of patients with LN, neither albuminuria nor CKD are discussed in the 2019 EULAR-ERA/EDTA recommendations for the management of LN or the more recent 2022 EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases. Indeed, the proteinuria target values discussed in the recommendations may be present in patients with severe CKD and a very high cardiovascular risk that may benefit from guidance detailed in the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. We propose that the recommendations should move from a conceptual framework of LN as an entity separate from CKD to a framework in which LN in considered a cause of CKD and evidence generated from large CKD trials applies unless demonstrated otherwise

Extracorporeal Techniques in End-Stage Kidney Disease

International audienceDuring the last decades, various strategies have been optimized to enhance clearance of a variable spectrum of retained molecules to ensure hemodynamic tolerance to fluid removal and improve long-term survival in patients affected by end-stage kidney disease. Treatment effects are the result of the interaction of individual patient characteristics with device characteristics and treatment prescription. Historically, the nephrology community aimed to provide adequate treatment, along with the best possible quality of life and outcomes. In this article, we analyzed blood purification techniques that have been developed with their different characteristics

Calciphylaxis-as a drug induced adverse event

INTRODUCTION: Calciphylaxis is a rare but devastating disease with a mortality rate up to 50% in 1 year. It is characterized by profoundly painful ischemic skin lesions and vascular calcification that affects predominantly patients with end stage renal disease. The use of certain medications is an important modifiable risk factor in calciphylaxis and discontinuation of these is a mainstay of treatment. AREAS COVERED: This review will provide an overview of calciphylaxis and will focus on how certain therapeutic agents can affect the risk of calcification and associated thrombosis, key processes involved in the development of calciphylaxis. EXPERT OPINION: Calciphylaxis treatment requires a multi-modal approach including prevention, risk factor management, wound care, reperfusion, and use of fibrinolytics and antioxidants. Patients with end stage renal disease represent the most affected population. This population often has multiple medications prescribed, some worth reconsidering before starting or continuing them. When possible, we recommend stopping all potentially contributing medications in patients with calciphylaxis, including warfarin, active vitamin D, calcium supplements, and iron

Curcumin Supplementation (Meriva^®) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease

Chronic kidney disease (CKD) subjects suffer from high risk of cardiovascular mortality, and any intervention preventing the progression of CKD may have an enormous impact on public health. In the last decade, there has been growing awareness that the gut microbiota (GM) can play a pivotal role in controlling the pathogenesis of systemic inflammatory state and CKD progression. To ameliorate the quality of life in CKD subjects, the use of dietary supplements has increased over time. Among those, curcumin has demonstrated significant in vitro anti-inflammatory properties. In this pilot study, 24 CKD patients and 20 healthy volunteers were recruited. CKD patients followed nutritional counselling and were supplemented with curcumin (Meriva®) for six months. Different parameters were evaluated at baseline and after 3–6 months: uremic toxins, metagenomic of GM, and nutritional, inflammatory, and oxidative status. Curcumin significantly reduced plasma pro-inflammatory mediators (CCL-2, IFN-γ, and IL-4) and lipid peroxidation. Regarding GM, after 6 months of curcumin supplementation, Escherichia-Shigella was significantly lower, while Lachnoclostridium was significant higher. Notably, at family level, Lactobacillaceae spp. were found significantly higher in the last 3 months of supplementation. No adverse events were observed in the supplemented group, confirming the good safety profile of curcumin phytosome after long-term administration

Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy

The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m2 difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN study

Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

Correction to: Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study (Internal and Emergency Medicine, (2018), 13, 5, (651-660), 10.1007/s11739-018-1835-9)

In the original publication, one of the ARAPACIS collaborators Dr. “Leonardo Di Gennaro” name has been erroneously mentioned as “Leonardo De Gennaro”