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.

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.

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The newly developed sodium‐glucose cotransporter 2 inhibitors (SGLT2is) effectively modulate glucose metabolism in diabetes. Although clinical data suggest that SGLT2is (empagliflozin, dapagliflozin, ertugliflozin, canagliflozin, ipragliflozin) are safe and protect against renal and cardiovascular events, very little attention has been dedicated to the effects of these compounds on different electrolytes. As with other antidiabetic compounds, some effects on water and electrolytes balance have been documented. Although the natriuretic effect and osmotic diuresis are expected with SGLT2is, these compounds may also modulate urinary potassium, magnesium, phosphate, and calcium excretion. Notably, they have had no effect on plasma sodium levels and promoted only small increases in serum potassium and magnesium concentrations in clinical trials. Moreover, SGLT2is may induce an increase in serum phosphate, FGF‐23, and PTH; reduce 1,25‐dihydroxyvitamin D; and generate normal serum calcium. Some published and preliminary reports, as well as unconfirmed reports have suggested an association with bone fractures. Some homeostasis perturbations are transient, whereas others may persist, suggesting that the administration of SGLT2is may affect electrolyte balances in exposed subjects. Although current evidence supports their safety, additional efforts are needed to elucidate the long‐term impact of these compounds on chronic kidney disease, mineral metabolism, and bone health. Indeed, the limited follow‐up studies and the heterogeneity of the case‐mix of different randomized controlled trials preclude a definitive answer on the impact of these compounds on long‐term outcomes such as the risk of bone fracture. Here we review the current understanding of the mechanisms involved in electrolyte handling and the available data on the clinical implications of electrolytes and mineral metabolism perturbations induced by SGLT2i administration. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Chronic kidney disease (CKD) patients have a higher risk of cardiovascular (CVD) morbidity and mortality compared to the general population. The links between CKD and CVD are not fully elucidated but encompass both traditional and uremic-related risk factors. The term CKD-mineral and bone disorder (CKD-MBD) indicates a systemic disorder characterized by abnormal levels of calcium, phosphate, PTH and FGF-23, along with vitamin D deficiency, decreased bone mineral density or altered bone turnover and vascular calcification. A growing body of evidence shows that CKD patients can be affected by subclinical vitamin K deficiency; this has led to identifying such a condition as a potential therapeutic target given the specific role of Vitamin K in metabolism of several proteins involved in bone and vascular health. In other words, we can hypothesize that vitamin K deficiency is the common pathogenetic link between impaired bone mineralization and vascular calcification. However, some of the most common approaches to CKD, such as (1) low vitamin K intake due to nutritional restrictions, (2) warfarin treatment, (3) VDRA and calcimimetics, and (4) phosphate binders, may instead have the opposite effects on vitamin K metabolism and storage in CKD patients.

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Fabry disease is classified as a rare X-linked disease caused by a complete or partial defect of enzyme alpha-galactosidase, due to GLA gene mutations. This disorder leads to intracellular globotriaosylceramide (Gb3) deposition associated with increased Gb3 plasma levels. Most of the symptoms of the disease, involving kidneys, heart and nervous system, result from this progressive Gb3 deposition. The incidence is estimated in 1/50,000 to 1/117,000 in males. Fabry nephropathy begins with microalbuminuria and/or proteinuria, which, in the classic form, appear from childhood. Thus, a progressive decline of renal function can start at a young age, and evolve to kidney failure, requiring dialysis or renal transplantation. Enzyme replacement therapy (ERT), available since 2001 for Fabry disease, has been increasingly introduced into the clinical practice, with overall positive short-term and long-term effects in terms of ventricular hypertrophy and renal function. Kidney transplantation represents a relevant therapeutic option for Fabry nephropathy management, for patients reaching end-stage renal disease, but little is known about long-term outcomes, overall patient survival or the possible role of ERT after transplant. The purpose of this review is to analyze the literature on every aspect related to kidney transplantation in patients with Fabry nephropathy: from the analysis of transplant outcomes, to the likelihood of disease recurrence, up to the effects of ERT and its possible interference with immunosuppression.