Role of Vitamin D in Vascular Complications and Vascular Access Outcome in Patients with Chronic Kidney Disease.

Vitamin D has been known for a long time as a major factor involved in the calcium- phosphate balance and homeostasis, along with parathyroid hormone (PTH). While vitamin D effects on calcium and phosphate are fully known, recent studies attempted to link vitamin D status and cardiovascular diseases. The involvement of vitamin D on vascular remodeling is mediated by several mechanisms such as activation of renin-angiotensin-aldosterone system (RAAS), cell proliferation and anti-apoptotic cell pathways. This correlation is highlighted by the fact that the activated form of vitamin D (1,25 (OH)2 D3) can be synthesized by the same endothelial cells, due to the constitutive presence of endothelial 1α-hydroxylase. Vitamin D reduces the expression of angiotensin 2 receptor (AT2R) on the endothelial cell surface (AT2R), leading to a cascade of events that result in the synthesis of vasodilators, such as nitric oxide. The activation of vitamin D receptors (VDRs) on endothelial cells induces changes in the metabolic activity of the endothelium and is responsible for cell survival, proliferation and neoangiogenesis. Moreover, altered signaling of VDR due to gene polymorphisms has been demonstrated in patients with cardiac disorders and chronic kidney disease (CKD). Recently, vascular access outcome has been associated with vitamin D status. Future studies will help to better define the need of vitamin D supplementation for a better cardiovascular as well as vascular access outcome in patients with CKD.

Sevalamer Hydrochloride, Sevelamer Carbonate and Lanthanum Carbonate: In Vitro and In Vivo Effects on Gastric Environment.

Hyperphosphatemia is common in patients with chronic renal failure. Phosphate binders are associated with gastric intolerance, representing the main reason of drug discontinuation. The aim of this study was to compare the effects in vitro and in vivo of sevelamer hydrochloride (SH), sevelamer carbonate (SC) and lanthanum carbonate (LC) on gastric microenvironment. We have also evaluated the efficacy and tolerability of these drugs in hemodialysis (HD) patients. In vitro analysis: Dissolution time, ability to uptake phosphorus, changes in pH starting from gastric milieu and the amount of carbon dioxide (CO(2)) produced were the variables analyzed. In vivo analysis: 24-h esophago-gastric pH measurement was evaluated in 24 HD patients treated with phosphate binders and proton pump inhibitor (PPI). In vitro: LC dissolved over a longer time compared with SC (58 ± 2.4 vs. 12 ± 0.6 min; P < 0.001) and SH (58 ± 2.4 vs. 10.3 ± 0.8 min; P < 0.001), determining the most alkaline pH. SC had the highest chelation power, binding 4.00 × 10(-9) mol/L of phosphoric acid. CO2 volume released was increased in LC solution (53.2 ± 7.8) compared to SC (33.9 ± 6.2; P < 0.001) and SH (2.3 ± 1.8; P < 0.001). In vivo: gastric pH increased after administration of phosphate binder. The most alkaline pH was recorded in patients treated with SC. The alkalinization of the gastric environment was not prevented by PPI therapy. 424 episodes of esophageal reflux were registered, 74% of them were alkaline. The LC group was characterized by the highest number of episodes. Sevelamer carbonate had a greater capacity and rapidity to chelate phosphorus, with a mild tolerability, due to its low CO(2) production. Sevelamer HCl was the most tolerated chelator because it did not produce CO(2), while lanthanum carbonate was the least soluble.

Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2* MRI assessment.

INTRODUCTION: Endocrinopathies and metabolic disorders-characterized ß thalassemic (ßT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in ßT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. PATIENTS AND METHODS: Seventy-two ßT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan-Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. RESULTS: High ferritin levels were observed in patients with hypothyroidism [1500 (872.5-2336.5) µg/L], hypogonadism [878 (334-2010) µg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367-1857) µg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = -0.64; P:0.0006) and liver (r = -0.40; P:0.03) values was observed. Patients with ferritin values above 1800 µg/L experienced a significantly faster evolution to hypothyroidism [log-rank (χ(2) ):7.7; P = 0.005], hypogonadism [log-rank (χ(2) ):10.7; P = 0.001], and multiple endocrinopathies [log-rank (χ(2) ):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P < 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. CONCLUSIONS: Ferritin represents a prognostic marker for ßT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility of hypothyroidism.

Vitamin D intoxication in two brothers: be careful with dietary supplements.

Vitamin D (VitD) intoxication, a well-known cause of hypercalcaemia in children, has renal, cardiac and neurological consequences. Iatrogenic or accidental administrations are the most common causes. We present two cases of hypervitaminosis D due to over-the-counter VitD supplement self-medication. A 12-year-old boy was hospitalised for abdominal pain, constipation and vomiting. Routine biochemistry indicated severe hypercalcaemia and renal failure. Plasma 25-OH VitD level was very high and parathyroid hormone was suppressed. Renal ultrasound showed nephrolithiasis. Hydration, diuretics and prednisone induced a progressive reduction of calcium levels. His brother, who was receiving the same treatment, was hospitalised although asymptomatic. Normal serum calcium and renal function were revealed, while 25-OH VitD was high and parathyroid hormone was suppressed. Renal ultrasound was within the normal range. Examination of the VitD content of the over-the-counter supplement revealed a higher amount than declared. VitD administration implies several risks and must be prescribed only when needed and under strict medical control.

Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy.

OBJECTIVE: Endocrine complications characterised patients with ß thalassaemia (ßT). In particular, thyroid dysfunction occurs frequently in ßT major, but its long-term natural history is poorly understood. DESIGN: A total of 72 ßT patients were followed for 8 years. The incidence of thyreopathies, defined as the primary study endpoint, was assessed. The aim of this study was to analyse the prognostic role of ferritin for thyreopathies in patients with major and intermedia ßT. The power of different iron chelators to treat iron overload and to prevent or reverse thyreopathies was also assessed. METHODS: Patients were treated with chelators with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying thyroid dysfunction in thalassaemic patients. Kaplan-Meier curves were generated to assess incidence of thyreopathy. Adjusted risk estimates for thyreopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. RESULTS: PATIENTS WITH THYROID DYSFUNCTION WERE CHARACTERISED BY HIGHER FERRITIN WHEN COMPARED WITH PATIENTS WITHOUT THYREOPATHIES (1500 (8722336) VS 513 (370698) G/L; P0.0001). PATIENTS WITH FERRITIN VALUES ABOVE 1800G/L EXPERIENCED A SIGNIFICANTLY FASTER EVOLUTION TO ENDPOINT (LOG-RANK ((2)): 7.7; P=0.005). Ferritin predicted high risk of thyroid dysfunction independently of confounding factors (hazard ratio: 1.20; P<0.0001). The intensification of chelation therapy led to an amelioration of thyroid function. CONCLUSIONS: Ferritin represents a prognostic marker for ßT patients and a predictive factor for progression to thyroid dysfunction. Intensive chelation therapy allows the prevention and reversibility of thyroid complications.

Can neutrophil gelatinase-associated lipocalin help depict early contrast material-induced nephropathy?

PURPOSE: To evaluate the utility of serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) in depicting an event of contrast material-induced nephropathy (CIN) in patients who received iodinated contrast media, gadoterate meglumine, or radiopharmaceutical technetium-99m ((99m)Tc) and to evaluate the protective effect exerted by isotonic saline infusion, sodium bicarbonate administration, or N-acetylcysteine administration. MATERIALS AND METHODS: Institutional ethics committee approval was given, and informed consent was obtained. One hundred twenty patients were enrolled in a prospective study and divided into three groups: iomeprol group, magnetic resonance (MR) imaging group (gadoterate meglumine), and renal scintigraphy group ((99m)Tc). They randomly received N-acetylcysteine, physiologic saline, or sodium bicarbonate. Receiver operating characteristic (ROC) analysis, Kaplan-Meier curves, and Cox proportional hazard regression analysis were used. RESULTS: In the MR imaging and renal scintigraphy groups, there were significant changes in serum creatinine and NGAL levels, and there were no cases of CIN. In the iomeprol group, an early rise in NGAL was found, while serum creatinine level changes occurred 24 hours after contrast material administration. At ROC analysis, NGAL showed high sensitivity and specificity (serum NGAL: area under the curve, 0.995; 95% confidence interval [CI]: 0.868, 0.992; urinary NGAL: area under the curve, 0.992; 95% CI: 0.925, 1.000) in identifying CIN 8 hours after iomeprol administration. Regression analysis showed that NGAL independently predicted CIN. Administration of N-acetylcysteine, sodium bicarbonate, or physiologic saline did not influence NGAL level. CONCLUSION: NGAL depicted CIN in patients who received iodinated contrast material within 8 hours of contrast material administration. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120578/-/DC1.

From chronic kidney disease to transplantation: the roles of obestatin.

BACKGROUND: Kidney transplantation is the therapy of choice in most cases of end stage renal disease. The purpose of the present study was to evaluate serum obestatin levels in kidney transplant recipients (Tx), compare levels in patients with renal failure (CKD) with those in healthy subjects (HS), and to assess the role of this hormone in energetic metabolism. PATIENTS AND METHODS: A total of 95 subjects were studied: 40 were Tx; 35 had CKD and 20 were HS. Inclusion criteria were age>18years and good allograft function. Patients with an inflammatory disease or a diagnosis of cancer were excluded from the study. RESULTS: Obestatin levels in Tx patients were significantly lower than in HS (3.5 [3-4.8] versus 11 [8.56-28.60] ng/mL; p<0.0001) and patients with CKD (3.5 [3-4.8] versus 4.7 [3, 5-6, 1] ng/mL; p=0.008). At univariate analysis, a direct correlation was found between obestatin and calcemia (p: 0.0001; r: 0.51), phosphoremia (p: 0.0005; r: 0, 46), calcium-phosphate product (p<0.0001; r:0.53), and parathormone (p: 0.01; r: 0.32), whereas significant inverse correlations were evidenced for BMI (p<0.0001; r: -0.52). At multivariate analysis, significance was maintained for the correlation between obestatin and phosphoremia (ß=0.47; p=0.008), for the calcium-phosphate product (ß=0.55; p=0.0005) and for BMI (ß=-0.53; p=0.01). CONCLUSION: Obestatin, present in lower levels in Tx patients than in CKD patients and HS, plays a role in energy metabolism, affecting BMI and the metabolism of calcium-phosphorus.

Malnutrition in the elderly patient on dialysis.

Approximately one-third of all dialysis patients have mild to moderate malnutrition, while 6-8% have severe malnutrition, which is associated with increased morbidity and mortality rates and numerous pre-existing factors directly correlated with, or existing prior to, replacement hemodialysis. However, moderate to severe malnutrition (present in 10-30% of dialysis patients) is a prevalent cause of death among the elderly. Many of these patients have a particularly unstable cardiovascular and metabolic status that, independent of any underlying uremia and/or dialysis, impacts negatively on both their quality of life and clinical status. Moreover, their condition is often further exacerbated by dialysis itself, with its acute (e.g., hypotension and sensorial alterations) and chronic complications, including an exacerbation of malnutrition and systemic vascular disease. Malnutrition can occur secondary not only to erroneous dietary choices or uremia, but it may also depend on the patient's level of tolerance to dialysis and on the dialysis modality. Despite the improvements made to dialysis techniques, the nutritional condition of elderly patients on dialysis for chronic renal failure remains a cause for concern. In this patient category, it is therefore mandatory to ensure the daily supervision of nutritional status and early control when the first signs of malnutrition appear.