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Background. Randomized trials have shown that early adoption of everolimus-based immunosuppressive regimens without a calcineurin inhibitor (CNI) improves long-term kidney graft function, but the optimal strategy for CNI minimization remains uncertain.Methods. In a prospective, randomized, multicentre, 12-month trial, 499 de novo kidney transplant patients were randomized at Month 3 to (i) remain on standard CNI (cyclosporine) therapy with mycophenolic acid, (ii) convert to everolimus with mycophenolic acid or (iii) start everolimus with reduced CNI and no mycophenolic acid (clinical trials registry: ClinicalTrials.gov-NCT00514514). Results. The primary endpoint, change in estimated glomerular filtration rate (eGFR) (Nankivell) from randomization to Month 12, was significantly greater in the CNI-free arm versus standard CNI therapy: mean difference 5.6 mL/min/1.73 m2 [95% confidence interval (CI) 2.8–8.3 mL/min/1.73 m2, P < 0.001]. The improvement in eGFR in the CNI-free arm was also higher than in the low-CNI group (mean difference 5.5 mL/min/1.73 m2, 95% CI 2.8–8.2 mL/min/1.73 m2, P < 0.001), while results were similar in the low-CNI and standard CNI arms. The post-randomization incidence of biopsy-proven acute rejection was 11.7%, 8.1% and 7.9% in the CNI-free, low-CNI and standard CNI groups, respectively (CNI-free versus standard CNI, P = 0.27; low-CNI versus standard CNI, P = 1.00). Adverse events led to study drug discontinuation in 28.7%, 15.5% and 15.2% of CNI-free, low-CNI and standard CNI patients, respectively. Conclusions. Everolimus initiation with CNI withdrawal at Month 3 after kidney transplantation achieves a significant improvement in renal function at 12 months, with a similar rate of acute rejection. [ABSTRACT FROM AUTHOR]

Background Patients on haemodialysis (HD) exhibit increased cardiovascular mortality associated with accelerated vascular calcification (VC). VC is influenced by inhibitors such as matrix Gla protein (MGP), a protein activated in the presence of vitamin K. HD patients exhibit marked vitamin K deficiency, and supplementation with vitamin K reduces inactive MGP levels in these patients. The VitaVasK trial analyses whether vitamin K1 supplementation affects the progression of coronary and aortic calcification in HD patients. Methods VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT No.: 2010-021264-14) that will include 348 HD patients in an open-label, two-arm design. After baseline multi-slice computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary calcification volume score of at least 100 will be randomized to continue on standard care or to receive additional supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration will be 18 months, and MSCT scans will be repeated after 12 and 18 months. Primary end points are the progression of thoracic aortic and coronary artery calcification (calculated as absolute changes in the volume scores at the 18-month MSCT versus the baseline MSCT). Secondary end points comprise changes in Agatston score, mitral and aortic valve calcification as well as major adverse cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to record MACE and all-cause mortality in the follow-up period at 3 and 5 years after treatment initiation. This trial may lead to the identification of an inexpensive and safe treatment or prophylaxis of VC in HD patients. [ABSTRACT FROM AUTHOR]

The differential diagnosis of hyponatraemia is manifold and includes hormonal disorders such as primary adrenal insufficiency or hypothyroidism. The diagnosis of adrenal insufficiency is always suggestive in cases of hypotension associated with hyponatraemia, hyperkalaemia and metabolic acidosis. We herein report a case of severe hyponatraemia in a patient with Addison's disease. The underlying cause was disseminated adrenal tuberculosis without any evidence of other organ involvement. To date, tuberculosis remains a frequent cause of adrenal insufficiency although the pathophysiology of adrenal tropism is poorly understood. [ABSTRACT FROM PUBLISHER]

: BackgroundAngiotensin II adversely affects endothelial function and NO availability. We analyzed the effect of AT1 receptor blockade on endothelium-dependent vasodilation and basal nitric oxide (NO) production and release in hypertensive patients.: Methods and resultsSixty patients (53 ± 10 years) with essential hypertension were randomized to 6 weeks of double-blind therapy with either valsartan (80 mg), hydrochlorothiazide (HCTZ) (25 mg), or placebo once daily. Basal NO production and release was assessed by measuring forearm blood flow (FBF) in response to intra-arterial infusion of NG-monomethyl-l-arginine (L-NMMA), and endothelium-dependent vasodilation by measuring FBF in response to intra-arterial administration of acetylcholine, respectively. Intra-arterial infusion of noradrenaline and sodium nitroprusside was used to assess endothelium-independent changes in FBF. Blood pressure (BP) similarly decreased with active treatments (P < .001). After valsartan treatment, the decrease of FBF in response to L-NMMA was augmented (4 μmol/min L-NMMA, −1.3 ± 1.2 after v −0.5 ± 1.1 mL/min/100 mL before therapy, P < .02; 8 μmol/min L-NMMA: −1.7 ± 1.3 after v −1.1 ± 1.2 mL/min 100 mL before therapy, P < .05). No improvement was found after placebo or HCTZ treatment. Changes in L-NMMA-induced decrease of FBF with valsartan treatment were not related to BP changes. Neither drug substantially modified the response of FBF induced by intra-arterial infusion of acetylcholine, noradrenaline, and sodium nitroprusside.: ConclusionsThe AT1 receptor blockade with valsartan improved basal NO production and release. The effect seems to be BP independent, as BP reduction with HCTZ failed to increase NO availability. [Copyright &y& Elsevier]

: Backgroundl-Arginine, the substrate of nitric oxide (NO) synthase, and NG-monomethyl-l-arginine (L-NMMA), a competitive inhibitor of endothelial NO synthase, are used to analyze endothelial function of the renal vasculature. However, little is known about the appropriate dose of l-arginine to be used and the duration of action of l-arginine and L-NMMA.: MethodsTwenty-nine healthy male subjects (age, 27 ± 1 years) were examined. In protocol 1 (N = 17), l-arginine at low (100 mg/kg) and high dose (250 mg/kg), and high-dose l-arginine combined either with L-NMMA (total dose, 4.25 mg/kg; N = 9) or placebo (N = 8) were given. In protocol 2 (N = 12), L-NMMA was given before l-arginine infusion (100 mg/kg). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured at rest and at the end of each infusion step.: ResultsIn protocol 1, l-arginine dose dependently increased RPF and GFR (RPF: 599 ± 19 v 630 ± 18 v 690 ± 24 mL/min, P <.05; GFR: 111 ± 3 v 115 ± 3 v 121 ± 3 mL/min, P <.01; for baseline, l-arginine 100 mg/kg and 250 mg/kg, respectively). However, these changes could not be antagonized by coinfusion of L-NMMA to l-arginine 250 mg/kg: RPF and GFR remained unchanged in both the placebo and the L-NMMA group. In protocol 2, L-NMMA decreased RPF (492 ± 18 v 567 ± 27 mL/min, P <.01) and increased GFR (122 ± 4 v 118 ± 3 mL/min, P <.05). These changes could only be partially reversed by subsequent infusion of l-arginine (RPF: 533 ± 15 mL/min; GFR: 121 ± 4 mL/min; both parameters P = NS v L-NMMA and v baseline).: Conclusionsl-arginine at a dose of 100 mg/kg is sufficient to analyze endothelial function of the renal vasculature. The prolonged effect of L-NMMA and l-arginine must be taken into account in study protocols using both substances. Thus, stimulation and blockade of NO synthase cannot be examined in the same protocol. [Copyright &y& Elsevier]