The link between homocysteine, folic acid and vitamin B12 in chronic kidney disease.

Patients with chronic kidney disease or end-stage renal disease experience tremendous cardiovascular risk. Cardiovascular events are the leading causes of death in these patient populations, thus the interest in non-traditional risk factors such as hyperhomocysteinemia, folic acid and vitamin B12 metabolism is growing. Hyperhomocysteinemia is commonly found in CKD patients because of impaired renal metabolism and reduced renal excretion. Folic acid, the synthetic form of vitamin B9, is critical in the conversion of homocysteine to methionine like vitamin B12. Folic acid has also been shown to improve endothelial function without lowering homocysteine, suggesting an alternative explanation for the effect of folic acid on endothelial function. Whether hyperhomocysteinemia represents a reliable marker of cardiovascular risk and cardiovascular mortality or a therapeutic target in this population remains unclear. However, it is reasonable to consider folic acid with or without methylcobalamin supplementation as appropriate adjunctive therapy in patients with CKD. The purpose of this review is to summarize the characteristics of homocysteine, folic acid, and vitamin B12 metabolism, the mechanism of vascular damage, and the outcome of vitamin supplementation on hyperhomocysteinemia in patients with CKD, ESRD, dialysis treatment, and in kidney transplant recipients.

Vitamin D Effects on Bone Homeostasis and Cardiovascular System in Patients with Chronic Kidney Disease and Renal Transplant Recipients.

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.

Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.

Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.

Nutritional vitamin D in CKD: Should we measure? Should we treat?

Vitamin Ddeficiency is frequently present in patients affected by chronic kidney disease (CKD). Experimental studies demonstrated that Vitamin D may play a role in the pathophysiology of diseases beyond mineral bone disorders in CKD (CKD-MBD). Unfortunately, the lack of large and interventional studies focused on the so called "non-classic" effects of 25(OH) Vitamin D supplementation in CKD patients, doesn't permit to conclude definitely about the beneficial effects of this supplementation in clinical practice. In conclusion, treatment of nutritional vitamin D deficiency in CKD may play a central role in both bone homeostasis and cardiovascular outcomes, but there is not clear evidence to support one formulation of nutritional vitamin D over another in CKD.

The Key Role of Phosphate on Vascular Calcification.

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance.

Risk and safety in context: medical pluralism and agency in childbirth in an eastern Moroccan oasis.

This article aims to improve the understandings of safety and risk in childbirth in Morocco from a critical medical anthropological perspective. It is based upon nine weeks' of fieldwork undertaken in the town of Ifli,(1) an oasis in Eastern Morocco, on the border with Algeria. Ethnographic material stemmed mainly from participant observation and semi-structured interviews conducted between April and July 2009. This research sheds light on the interplay between the socio-cultural context and the broader political economy of health in shaping the knowledge and practices of childbirth. The core issues emerging from the fieldwork are the local concepts of risk in the birthing process through mothers' and birth attendants' experiences within medical pluralistic frames of reference. This article shall argue that ethnographic insights can play a crucial role not only in understanding socio-cultural dimensions of childbirth, but also in implementing novel approaches to reproductive health care in this area, such as the exchange of experiences between trained and local, non-trained midwives.(2).

Tubular dysfunction after peritonectomy and chemohyperthermic treatment with cisplatin.

Peritoneal carcinomatosis has always been regarded as a contraindication in traditional cancer surgery treatment; however, good results have been reported by using new combined medical-surgical loco-regional techniques. Peritonectomy and chemohyperthermic perfusion with cisplatinum (CIIP) seem to play a central role in obtaining a better survival rate than with the traditional procedures, even though there is a cisplatinum nephrotoxic effect. The aim of this study was to investigate entity and type of renal injury after CIIP. Forty-two patients (12 males and 30 females) with recurrent or primary peritoneal carcinomatosis who underwent peritonectomy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy with cisplatin were enrolled. A significant worsening in renal function was observed on the third post-operative day and this condition then persisted for three months. A reduction in estimated-Glomerular Filtration Rate (e-GFR) and an alteration in the albumin:creatinine ratio proved tubular injury. On the third post-operative day after cisplatinum administration, a high toxicity peak was found following platinum free fraction excretion. Proximal tubular injury was confirmed even at the three month analysis. A significant correlation between the total protein reduction rate and the decrease in renal function was established. In relation to that, the platinum free fraction could increase because of a binding protein shortage and the nephrotoxic effect could be enhanced due to platinum accumulation within the post-operative period. This finding suggests that the higher the protein reduction is, the lower the e-GFR determination is at three months.