Circulating Klotho levels: clinical relevance and relationship with tissue Klotho expression

Klotho is a protein that exerts paracrine and endocrine functions. In chronic kidney disease (CKD), its expression is decreased in several tissues. This decrease probably plays important roles in various complications associated with CKD, in both a fibroblast growth factor-23 (FGF23)-dependent and an FGF23-independent manner. The clinical diagnosis of Klotho deficiency is not easy. The relevance of circulating Klotho levels, if any, needs to be adequately defined. Serum Klotho may not reflect tissue Klotho concentration

miR-223: An inflammatory oncomiR enters the cardiovascular field

AbstractMicroRNAs (miRNAs) are small, noncoding RNAs of 18–22 nucleotides in length that regulate post-transcriptional expression by base-pairing with target mRNAs. It is now clearly established that miRNAs are involved in most of the cell's physiopathological processes (including carcinogenesis and metabolic disorders). This review focuses on miR-223, which was first described as a modulator of hematopoietic lineage differentiation. We outline the role of miR-223 deregulation in several types of cancers and highlight its inclusion in a newly identified and fast-growing family of miRNAs called oncomiRs. We then look at miR-223's emerging role in inflammatory and metabolic disorders, with a particular focus on muscle diseases, type II diabetes, atherosclerosis and vascular calcification. miR-223 is one of the growing number of RNA biomarkers of various human metabolic diseases and is thus of special interest to both researchers and clinicians in the cardiovascular field

Maintenance haemodialysis with low dialysate flow rates in Senegal

Introduction: The objective of the study reported here was to demonstrate that maintenance haemodialysis using a reduced dialysate flow rate of 300 mL/min (RQD) is not inferior to haemodialysis using the standard flow rate of 500 mL/min (SQD) in respect of the delivered dose of dialysis. Methods: A prospective, single-centre, sequential study was performed at the haemodialysis  centre of Pikine Hospital in Dakar. Twenty patients were included. During the first week, three haemodialysis sessions were performed with SQD and during the second week three haemodialysis  sessions were conducted with RQD for each patient. Results: For SQD, the mean eKt/V was 1.38 ± 0.58. There were 38 (63%) sessions with eKt/V greater than 1.2 and 16 patients (80%) had adequate dialysis, based on the average eKt/V. For RQD, the mean eKt/V was 1.2 ± 0.43 with 25 sessions (42%) having an eKt/V greater than 1.2. There were 11 patients (55%) with adequate dialysis. The dialysis dose was higher with the SQD prescription (P < 0.001). Ten patients with dry weight ≤60 kg had adequate dialysis with RQD. Cases of hypokalaemia were significantly higher with the SQD (P = 0.001). Conclusions: RQD appears to be inferior in terms of dialysis dose. However, for patients with dry weight ≤60 kg, adequate dialysis could be delivered with RQD, consequently allowing substantial saving of water in haemodialysis

Estimated glomerular filtration rate is a poor predictor of the concentration of middle molecular weight uremic solutes in chronic kidney disease

Background: Uremic solute concentration increases as Glomerular Filtration Rate (GFR) declines. Weak associations were demonstrated between estimated GFR (eGFR) and the concentrations of several small water-soluble and protein-bound uremic solutes (MW500Da). Materials and Methods: In 95 CKD-patients (CKD-stage 2-5 not on dialysis), associations between different eGFR-formulae (creatinine, CystatinC-based or both) and the natural logarithm of the concentration of several LMWP's were analyzed: i.e. parathyroid hormone (PTH), Cystatin C (CystC), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), leptin, retinol binding protein (RbP), immunoglobin light chains kappa and lambda (Ig-kappa and Ig-lambda), beta-2-microglobulin (beta M-2), myoglobin and fibroblast growth factor-23 (FGF-23)). Results: The regression coefficients (R-2) between eGFR, based on the CKD-EPI-Crea-CystC-formula as reference, and the examined LMWP's could be divided into three groups. Most of the LMWP's associated weakly (R-2 0.7). Almost identical R-2-values were found per LMWP for all eGFR-formulae, with exception of CystC and beta M-2 which showed weaker associations with creatinine-based than with CystC-based eGFR. Conclusion: The association between eGFR and the concentration of several LMWP's is inconsistent, with in general low R-2-values. Thus, the use of eGFR to evaluate kidney function does not reflect the concentration of several LMWP's with proven toxic impact in CKD

A snapshot of European registries on chronic kidney disease patients not on kidney replacement therapy

Non peer reviewe

Changes in clinical indicators related to the transition from dialysis to kidney transplantation-data from the ERA-EDTA Registry

Background. Kidney transplantation should improve abnormalities that are common during dialysis treatment, like anaemia and mineral and bone disorder. However, its impact is incompletely understood. We therefore aimed to assess changes in clinical indicators after the transition from chronic dialysis to kidney transplantation. Methods. We used European Renal Association-European Dialysis and Transplant Association Registry data and included adult dialysis patients for whom data on clinical indicators before and after transplantation (2005-15) were available. Linear mixed models were used to quantify the effect of transplantation and of time after transplantation for each indicator. Results. In total, 16 312 patients were included. The mean age at transplantation was 50.1 (standard deviation 14.2) years, 62.9% were male and 70.2% were on haemodialysis before transplantation. Total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides increased right after transplantation but decreased thereafter. All other indicators normalized or approached the target range soon after transplantation and these improvements were sustained for the first 4 years of follow-up. In patients with higher estimated glomerular filtration rate (eGFR) levels (30-60 and >60 mL/min/1.73 m(2)), the improvement of haemoglobin, ferritin, ionized calcium, phosphate, parathyroid hormone, HDL cholesterol, triglycerides, albumin and C-reactive protein levels was more pronounced than in patients with a lower eGFR ( Conclusions. Except for total cholesterol, LDL cholesterol and triglycerides, all clinical indicators improved after transplantation. These improvements were related to eGFR. Nevertheless, values remained out of range in a considerable proportion of patients and anaemia and hyperparathyroidism were still common problems. Further research is needed to understand the complex relationship between eGFR and the different clinical indicators.Peer reviewe

Effect of oral calcium carbonate on aortic calcification in apolipoprotein E-deficient (apoE−/−) mice with chronic renal failure

Background. In chronic kidney disease (CKD) patients, the intake of calcium-based phosphate binders is associated with a marked progression of coronary artery and aortic calcification, in contrast to patients receiving calcium-free phosphate binders. The aim of this study was to reexamine the role of calcium carbonate in vascular calcification and to analyse its effect on aortic calcification-related gene expression in chronic renal failure (CRF). Methods. Mice deficient in apolipoprotein E underwent either sham operation or subtotal nephrectomy to create CRF. They were then randomly assigned to one of the three following groups: a control non-CRF group and a CRF group fed on standard diet, and a CRF group fed on calcium carbonate enriched diet, for a period of 8 weeks. Aortic atherosclerotic plaque and calcification were evaluated using quantitative morphologic image processing. Aortic gene and protein expression was examined using immunohistochemistry and Q-PCR methods. Results. Calcium carbonate supplementation was effective in decreasing serum phosphorus but was associated with a higher serum calcium concentration. Compared with standard diet, calcium carbonate enriched diet unexpectedly induced a significant decrease of both plaque (p < 0.05) and non-plaque-associated calcification surface (p < 0.05) in CRF mice. It also increased osteopontin (OPN) protein expression in atherosclerotic lesion areas of aortic root. There was also a numerical increase in OPN and osteoprotegerin gene expression in total thoracic aorta but the difference did not reach the level of significance. Finally, calcium carbonate did not change the severity of atherosclerotic lesions. Conclusion. In this experimental model of CRF, calcium carbonate supplementation did not accelerate but instead decreased vascular calcification. If our observation can be extrapolated to humans, it appears to question the contention that calcium carbonate supplementation, at least when given in moderate amounts, necessarily enhances vascular calcification. It is also compatible with the hypothesis of a preponderant role of phosphorus over that of calcium in promoting vascular calcification in CR