LVNC and HCM may appear as overlapping entities. The ACTC E101K mutation should be considered in the genetic diagnosis of LVNC, apical HCM, and septal defects.

The prevalence of inflammation is high in pre-dialysis patients. High serum CRP levels predict a constant inflammatory state on follow-up. As occurs in dialysis patients, pre-dialysis inflammation predicts lower serum albumin concentration, poorer response to Epo, and a higher hospitalization rate. The decline in renal function does not seem to be related to the inflammatory state. Mortality was not affected on short-term follow-up.

Bone loss and increased fractures are common complications in chronic kidney disease. Because Wnt pathway activation is essential for normal bone mineralization, we assessed whether Wnt inhibition contributes to high-phosphorus-induced mineralization defects in uremic rats. By week 20 after 7/8 nephrectomy, rats fed a high-phosphorus diet had the expected high serum creatinine, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23) levels and low serum calcium. There was a 15% reduction in tibial mineral density and a doubling of bone cortical porosity compared to uremic rats fed a normal-phosphorus diet. The decreases in tibial mineral density were preceded by time-dependent increments in gene expression of bone formation (Osteocalcin and Runx2) and resorption (Cathepsin K) markers, which paralleled elevations in gene expression of the Wnt inhibitors Sfrp1 and Dkk1 in bone. Similar elevations of Wnt inhibitors plus an increased phospho-β-catenin/β-catenin ratio occurred upon exposure of the osteoblast cell line UMR106-01 either to uremic serum or to the combination of parathyroid hormone, FGF23, and soluble Klotho, at levels present in uremic serum. Strikingly, while osteoblast exposure to parathyroid hormone suppressed the expression of Wnt inhibitors, FGF23 directly inhibited the osteoblastic Wnt pathway through a soluble Klotho/MAPK-mediated process that required Dkk1 induction. Thus, the induction of Dkk1 by FGF23/soluble Klotho in osteoblasts inactivates Wnt/β-catenin signaling. This provides a novel autocrine/paracrine mechanism for the adverse impact of high FGF23 levels on bone in chronic kidney disease.

Background/Aim: Sodium and water retention is common in peritoneal dialysis patients and contributes to cardiovascular disease. As peritoneal sodium removal depends partly on dwell time, and automated peritoneal dialysis (APD) often uses short dwell time exchanges, the aim of this study was to compare the 24-hour peritoneal sodium removal in APD and standard continuous ambulatory peritoneal dialysis (CAPD) patients and to analyze its possible influence on blood pressure control. Methods: A total of 53 sodium balance studies (30 in APD and 23 in CAPD) were performed in 36 stable peritoneal dialysis patients. The 24-hour net removal of sodium was calculated as follows: M = ViCi – VdCd, where Vd is the 24-hour drained volume, Cd is the solute sodium concentration in Vd, Vi is the amount of solution used during a 24-hour period, and Ci is the sodium concentration in Vi. Peritoneal sodium removal was compared between APD and CAPD patients. Residual renal function, serum sodium concentration, daily urinary sodium losses, weekly peritoneal Kt/V and creatinine clearance, 4-hour dialysate/plasma creatinine ratio, proportion of hypertonic solutions, net ultrafiltration, systolic and diastolic blood pressures, and need for antihypertensive therapy were also compared between the groups. Results: Peritoneal sodium removal was higher (p < 0.001) in CAPD than in APD patients. There were no significant differences in residual renal function, serum sodium concentration, urinary sodium losses, peritoneal urea or creatinine clearances, 4-hour dialysate/plasma creatinine ratio, or proportion of hypertonic solutions between groups. The net ultrafiltration was higher in CAPD patients and correlated strongly (r = 0.82; p < 0.001) with peritoneal sodium removal. In APD patients, peritoneal sodium removal increased significantly only in those patients with a second daytime exchange. The systolic blood pressure was higher (p < 0.05) in APD patients, and the proportion of patients with antihypertensive therapy was also higher in APD patients, although no significant relationship between blood pressure values and amount of peritoneal sodium removal was found. Conclusions: The 24-hour sodium removal is higher in CAPD than in APD patients, and there is a trend towards better hypertension control in CAPD patients. As hypertension control and volume status are important indices of peritoneal dialysis adequacy, our results have to be considered in the choice of the peritoneal dialysis modality.

Vascular calcification is a frequent cause of morbidity and mortality in patients with CKD and the general population. The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyperphosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or highphosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and highcalcium and -phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, miR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.

BackgroundPentavalent antimonials have been the first line treatment for dermal leishmaniasis in Colombia for over 30 years. Miltefosine is administered as second line treatment since 2005. The susceptibility of circulating populations of Leishmania to these drugs is unknown despite clinical evidence supporting the emergence of resistance.Methodology/Principal Findings In vitro susceptibility was determined for intracellular amastigotes of 245 clinical strains of the most prevalent Leishmania Viannia species in Colombia to miltefosine (HePC) and/or meglumine antimoniate (SbV); 163, (80%) were evaluated for both drugs. Additionally, susceptibility to SbV was examined in two cohorts of 85 L. V. panamensis strains isolated between 1980–1989 and 2000–2009 in the municipality of Tumaco. Susceptibility to each drug differed among strains of the same species and between species. Whereas 68% of L. V. braziliensis strains presented in vitro resistance to HePC, 69% were sensitive to SbV. Resistance to HePC and SbV occurred respectively, in 20% y 21% of L. panamensis strains. Only 3% of L. V. guyanensis were resistant to HePC, and none to SbV. Drug susceptibility differed between geographic regions and time periods. Subpopulations having disparate susceptibility to SbV were discerned among L. V. panamensis strains isolated during 1980–1990 in Tumaco where resistant strains belonged to zymodeme 2.3, and sensitive strains to zymodeme 2.2.Conclusions/SignificanceLarge scale evaluation of clinical strains of Leishmania Viannia species demonstrated species, population, geographic, and epidemiologic differences in susceptibility to meglumine antimoniate and miltefosine, and provided baseline information for monitoring susceptibility to these drugs. Sensitive and resistant clinical strains within each species, and zymodeme as a proxy marker of antimony susceptibility for L. V. panamensis, will be useful in deciphering factors involved in susceptibility and the distribution of sensitive and resistant populations.

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Our findings demonstrated that the three VDRAs used induced similar changes in bone metabolic parameters and LVH. In addition, paricalcitol was the only VDRA which showed a relevant beneficial effect in the reduction of myocardial fibrosis, a key factor in the myocardial dysfunction in CKD patients.