Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a growing worldwide epidemic. Patients face lifelong therapy to control hyperglycemia and prevent the associated complications. There are many medications, with varying mechanisms, available for the treatment of T2DM, but almost all target the declining insulin sensitivity and secretion that are associated with disease progression. Medications with such insulin-dependent mechanisms of action often lose efficacy over time, and there is increasing interest in the development of new antidiabetes medications that are not dependent upon insulin. One such approach is through the inhibition of renal glucose reuptake. Dapagliflozin, the first of a class of selective sodium glucose cotransporter 2 inhibitors, reduces renal glucose reabsorption and is currently under development for the treatment of T2DM. Here, we review the literature relating to the preclinical and clinical development of dapagliflozin

Nutrition aspects in children receiving maintenance hemodialysis: impact on outcome

Children with end-stage renal disease (ESRD) have rates of mortality estimated to be 30-times higher than expected for age compared with those of healthy children. Physical manifestations of under-nutrition, such as body mass index (BMI) and low height standard deviation score (SDS), have been associated with increased risk of mortality. Traditional measures, such as height, weight and serum albumin concentration, may not be accurate indicators to assess the nutritional status of children receiving maintenance hemodialysis. Normalized protein catabolic rate (nPCR) has emerged as a better marker of nutritional status of such children. Meeting the special nutritional needs of these children often requires nutritional supplementation, by either the enteral or the parenteral route. Recently, in children receiving maintenance hemodialysis who are malnourished, intradialytic parenteral nutrition (IDPN) has been utilized as a means to provide additional protein and calories. This article is a state-of-the-art review of malnutrition in children receiving maintenance hemodialysis, with special focus on outcome, nPCR and IDPN

Plasma Levels of Middle Molecules to Estimate Residual Kidney Function in Haemodialysis without Urine Collection

© 2015 Vilar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/Licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.BACKGROUND: Residual Kidney Function (RKF) is associated with survival benefits in haemodialysis (HD) but is difficult to measure without urine collection. Middle molecules such as Cystatin C and β2-microglobulin accumulate in renal disease and plasma levels have been used to estimate kidney function early in this condition. We investigated their use to estimate RKF in patients on HD. DESIGN: Cystatin C, β2-microglobulin, urea and creatinine levels were studied in patients on incremental high-flux HD or hemodiafiltration(HDF). Over sequential HD sessions, blood was sampled pre- and post-session 1 and pre-session 2, for estimation of these parameters. Urine was collected during the whole interdialytic interval, for estimation of residual GFR (GFRResidual = mean of urea and creatinine clearance). The relationships of plasma Cystatin C and β2-microglobulin levels to GFRResidual and urea clearance were determined. RESULTS: Of the 341 patients studied, 64% had urine output>100 ml/day, 32.6% were on high-flux HD and 67.4% on HDF. Parameters most closely correlated with GFRResidual were 1/β2-micoglobulin (r2 0.67) and 1/Cystatin C (r2 0.50). Both these relationships were weaker at low GFRResidual. The best regression model for GFRResidual, explaining 67% of the variation, was: GFRResidual = 160.3 · (1/β2m) - 4.2. Where β2m is the pre-dialysis β2 microglobulin concentration (mg/L). This model was validated in a separate cohort of 50 patients using Bland-Altman analysis. Areas under the curve in Receiver Operating Characteristic analysis aimed at identifying subjects with urea clearance≥2 ml/min/1.73 m2 was 0.91 for β2-microglobulin and 0.86 for Cystatin C. A plasma β2-microglobulin cut-off of ≤19.2 mg/L allowed identification of patients with urea clearance ≥2 ml/min/1.73 m2 with 90% specificity and 65% sensitivity. CONCLUSION: Plasma pre-dialysis β2-microglobulin levels can provide estimates of RKF which may have clinical utility and appear superior to cystatin C. Use of cut-off levels to identify patients with RKF may provide a simple way to individualise dialysis dose based on RKF.Peer reviewe

Nutrition in children with CRF and on dialysis

The objectives of this study are: (1) to understand the importance of nutrition in normal growth; (2) to review the methods of assessing nutritional status; (3) to review the dietary requirements of normal children throughout childhood, including protein, energy, vitamins and minerals; (4) to review recommendations for the nutritional requirements of children with chronic renal failure (CRF) and on dialysis; (5) to review reports of spontaneous nutritional intake in children with CRF and on dialysis; (6) to review the epidemiology of nutritional disturbances in renal disease, including height, weight and body composition; (7) to review the pathological mechanisms underlying poor appetite, abnormal metabolic rate and endocrine disturbances in renal disease; (8) to review the evidence for the benefit of dietetic input, dietary supplementation, nasogastric and gastrostomy feeds and intradialytic nutrition; (9) to review the effect of dialysis adequacy on nutrition; (10) to review the effect of nutrition on outcome