Patients affected by chronic kidney disease (CKD) or end-stage renal disease (ESRD) experience a huge cardiovascular risk and cardiovascular events represent the leading causes of death. Since traditional risk factors cannot fully explain such increased cardiovascular risk, interest in non-traditional risk factors, such as hyperhomocysteinemia and folic acid and vitamin B12 metabolism impairment, is growing. Although elevated homocysteine blood levels are often seen in patients with CKD and ESRD, whether hyperhomocysteinemia represents a reliable cardiovascular and mortality risk marker or a therapeutic target in this population is still unclear. In addition, folic acid and vitamin B12 could not only be mere cofactors in the homocysteine metabolism; they may have a direct action in determining tissue damage and cardiovascular risk. The purpose of this review was to highlight homocysteine, folic acid and vitamin B12 metabolism impairment in CKD and ESRD and to summarize available evidences on hyperhomocysteinemia, folic acid and vitamin B12 as cardiovascular risk markers, therapeutic target and risk factors for CKD progression.

The novel coronavirus, called SARS-CoV-2 has been declared a pandemic on March 2020, by the World Health Organization. Older individuals and patients with comorbid conditions such as hypertension, heart disease, diabetes, lung disease, chronic kidney disease (CKD), and immunologic diseases are at higher risk of contracting this severe infection. In particular, patients with advanced CKD constitute a vulnerable population and a challenge in the prevention and control of the disease. Home-based renal replacement therapies offer opportunity to manage patients remotely, thus reducing the likelihood of infection due to direct human interaction. Patients are seen less frequently, limiting the close interaction between patients and healthcare workers who may contract and spread the disease. On the other hand, while home dialysis is reasonable selection at his time due to the advantage of isolation of patients, measures must be assured to implement the program. Despite its logistical benefits, outpatient hemodialysis also presents certain challenges during times of crises such as COVID 19 pandemic and potentially future ones.

Immune disorders, involving both innate and adaptive response, are common in patients with end-stage renal disease under chronic hemodialysis. Endogenous and exogenous factors, such as uremic toxins and the extracorporeal treatment itself, alter the immune balance, leading to chronic inflammation and higher risk of cardiovascular events. Several studies have previously described the immune effects of chronic hemodialysis and the possibility to modulate inflammation through more biocompatible dialyzers and innovative techniques. On the other hand, very limited data are available on the possible immunological effects of a single hemodialysis treatment. In spite of the lacking information about the immunological reactivity related to a single session, there is evidence to indicate that mediators of innate and adaptive response, above all complement cascade and T cells, are implicated in immune system modulation during hemodialysis treatment. Expanding our understanding of these modulations represents a necessary basis to develop pro-tolerogenic strategies in specific conditions, like hemodialysis in septic patients or the last session prior to kidney transplant in candidates for receiving a graft.

Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant.

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs that, in addition to emerging as an effective hypoglycemic treatment, have been shown to improve, in several trials, both renal and cardiovascular outcomes. In consideration of the renal site of action and the associated osmotic diuresis, a negative sodium balance has been postulated during SGLT2i administration. Although it is presumable that sodium and water depletion may contribute to some positive actions of SGLT2i, evidence is far from being conclusive and the real physiologic effects of SGLT2i on sodium remain largely unknown. Indeed, no study has yet investigated how SGLT2i change sodium balance in the long term and especially the pathways through which the natriuretic effect is expressed. Furthermore, recently, several experimental studies have identified different pathways, not directly linked to tubular sodium handling, which could contribute to the renal and cardiovascular benefits associated with SGLT2i. These compounds may also modulate urinary chloride, potassium, magnesium, phosphate, and calcium excretion. Some changes in electrolyte homeostasis are transient, whereas others may persist, suggesting that the administration of SGLT2i may affect mineral and electrolyte balances in exposed subjects. This paper will review the evidence of SGLT2i action on sodium transporters, their off-target effects and their potential role on kidney protection as well as their influence on electrolytes and mineral homeostasis.

Background/Aim: Acute kidney injury is an important cause of mortality in very-low-birth-weight (VLBW) preterm infants. As in the general population, the detection of renal damage cannot rely on the measurement of serum creatinine, since it has been demonstrated to be a weak predictor and a delayed indicator of kidney function deterioration. However, several candidate biomarkers have failed to prove sufficient specificity and sensitivity for a routine clinical use because of the poor awareness of their biological role. This study was aimed to investigate the impact of different maternal and neonatal conditions on several renal biomarkers in VLBW preterm infants during the first week of life. Patients and Methods: Preterm infants<32 weeks' gestation and <1500g were enrolled. We measured urinary biomarkers kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, epidermal growth factor (EGF) and osteopontin (OPN) on the 1 st , 3 rd , and 7 th day after birth. Results: Thirty-tree infants were included. The multivariate analysis showed a significant association between gestational age, the presence of patent ductus arteriosus, antenatal maternal hypertension and the levels of urinary biomarkers. Conclusion: There is a possible relation between early biomarkers of renal injury and antenatal, perinatal and post-natal characteristics in VLBW preterm infants during the first week of life. Preterm birth is burdened by high rates of perinatal morbidity and mortality worldwide (1). With an estimated incidence of 12-18%, acute kidney injury (AKI) is among the main causes of mortality in the preterm population, and represents an independent predictor of mortality even after adjustment for confounding variables, namely comorbidities, interventions and demographic characteristics (2, 3). Preterm birth is also associated with an increased risk of cardiovascular and chronic kidney disease in adulthood; this poses important challenges for the clinicians to detect as soon as possible developmental and functional abnormalities that could affect lifetime (4, 5). In humans and experimental animals, however, measurable changes in serum creatinine and glomerular filtration rates can be evident only after a remarkable reduction in kidney function (less than 50-80% of normal values), being thus insensitive to detect subclinical renal damage. Moreover, serum creatinine levels can be influenced by several factors, such as gender, age, hydration state, muscle mass, ongoing medications and endogenous metabolites (e.g., bilirubin) (3, 6). In the neonatal population, AKI definitions based on serum creatinine are susceptible to specific additional limitations: in the first days of life, serum creatinine may reflect the maternal kidney function (7, 8) and it is not able to distinguish pre-renal injuries, which are often reversible and transient, from intrinsic renal injuries (9). Moreover, serum creatinine does not provide specific information on the type of kidney insult (e.g., toxic, infectious, ischemic...

Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease–mineral and bone disorder (CKD–MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.