Bioimpedance spectroscopy for assessment of volume status in patients before and after general anaesthesia

BackgroundTechnically assisted assessment of volume status before surgery may be useful to direct intraoperative fluid administration. We therefore tested a recently developed whole-body bioimpedance spectroscopy device to determine pre- to postoperative fluid distribution.MethodsUsing a three-compartment physiologic tissue model, the body composition monitor (BCM, Fresenius Medical Care, Germany) measures total body fluid volume, extracellular volume, intracellular volume and fluid overload as surplus or deficit of 'normal' extracellular volume. BCM-measurements were performed before and after standardized general anaesthesia for gynaecological procedures (laparotomies, laparoscopies and vaginal surgeries). BCM results were blinded to the attending anaesthesiologist and data analysed using the 2-sided, paired Student's t-test and multiple linear regression.ResultsIn 71 females aged 45 ± 15 years with body weight 67 ± 13 kg and Duration of anesthesia 154 ± 69 minutes [corrected] duration of anaesthesia 154 ± 68 min, pre- to postoperative fluid overload increased from -0.7 ± 1.1 L to 0.1 ± 1.0 L, corresponding to -5.1 ± 7.5% and 0.8 ± 6.7% of normal extracellular volume, respectively (both pConclusionsRoutine intraoperative fluid administration results in a significant, and clinically meaningful increase in the extracellular compartment. BCM-measurements yielded plausible results and may become useful to guide intraoperative fluid therapy in future studies

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.</p> <p>Methods/Design</p> <p>This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.</p> <p>Discussion</p> <p>NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00980356</p

The EGF Receptor controls osteoblast differentiation by negatively regulating IGF 1/mTOR signalling

Mäuse, bei denen der epidermale Wachstumsfaktor Rezeptor (EGF-Rezeptor) deletiert wurde sterben innerhalb eines Monates nach ihrer Geburt und bleiben kleiner als Wildtyp-Mäuse, in Folge eines Wachstumsdefekts ihrer Röhrenknochen. Die molekulare Wirkung des EGF-Rezeptors auf die Knochenentwicklung ist aber unklar. Im Rahmen meiner PhD Arbeit habe ich den Knochenphänotyp von EGF-Rezeptor Knock-out Mäusen zu unterschiedlichen Zeitpunkten vor dem 25. Lebenstag untersucht. Die Resultate dieser Arbeit zeigten, dass der Wachstumsdefekt in den Knochen von EGF-Rezeptor Knock-out Mäusen durch eine Interaktion des EGF-Rezeptors mit dem Insulin Wachstumsfaktor 1 (IGF1)/mammalian Target of Rapamycin (mTOR)-Signaltransduktionswegs zustande kommt. Osteoblasten, welche aus EGF-Rezeptor Knock-out Mäusen isoliert wurden proliferierten in der Zellkultur weniger stark als die Wildtyp-Osteoblasten, waren aber gleichzeitig hyperdifferenziert, wobei sie höhere Konzentrationen von Proteinen des mTOR-Signaltransduktionsweges, unter anderem 4EBP und IGF1R, aufwiesen. Die pharmakologische Hemmung von mTOR verringerte die Osteoblasten-Differenzierung in EGF-Rezeptor Knock-out Osteoblasten, bis auf ein ähnliches Niveau wie bei Wildtyp-Zellen, was darauf schliessen liess, dass die Überaktivierung von mTOR für die beobachtete Hyperdifferenzierung verantwortlich war. Die Stimulierung von Wildtyp Osteoblasten mit IGF1 verstärkte die Differenzierung, wohingegen EGF die Differenzierung drastisch verminderte. In der Histologie imponierten die EGF-Rezeptor Knock-out Mäuse osteopenisch, und ihre Röhrenknochen wiesen dysorganisierte, ungerichtete Mineralisierung auf. Kokultur-Experimente mit Osteoblasten und Osteoklasten deuteten darauf hin, dass dies die Folge eines Osteoblasten-Defekts war, nicht eines Osteoklasten-Defekts. In Summe zeigen die vorgelegten Daten einen wahrscheinlichen Mechanismus für den Knochenphänotyp in EGF-Rezeptor Knock-out Mäusen auf, wobei der IGF1/mTOR-Signalweg durch den EGF-Rezeptor gehemmt wird. Diese Hemmung scheint in der normalen Knochenentwicklung dafür notwendig zu sein, eine balancierte Osteoblasten-Proliferation und Osteobasten-Differenzierung zu gewährleisten.Epidermal growth factor receptor knock-out (EGFR-/-) mice die within one month after birth and remain smaller than their wild type littermates, as a consequence of a growth defect which also affects their long bones. The molecular effect of the EGFR on osteodevelopment, however, has remained unclear. During my PhD thesis work, I analyzed the skeletal phenotype of EGFR-/- mice at various time-points before postnatal day 25. The results of this work showed that the growth defect which was observed in the bones of EGFR-/- mice may depend upon an interaction between the EGFR and the insulin-like growth factor-1 (IGF1)/mammalian target of rapamycin (mTOR)-pathway. Osteoblasts isolated from EGFR-/- mice in cell culture proliferated less than wild type osteoblasts, but were hyperdifferentiated and overexpressed several mTOR-pathway proteins, such as 4EBP and the IGF1-receptor (IGF1R). Pharmacological inhibition of mTOR decreased osteoblast differentiation in EGFR-/- osteoblasts to similar levels as in wild type, suggesting that mTOR-overactivation was responsible for the observed hyperdifferentiation. Additionally, stimulation of wild type osteoblasts with IGF1 enhanced, whereas stimulation with EGF reduced differentiation. At the histological level, EGFR-/- mice were osteopenic with bones exhibiting disorganized and irregular mineralization. Experiments with osteoblasts and osteoclasts in co-culture additionally revealed that the in vivo pattern represented an osteoblastic rather than an osteoclastic defect. In summary, the present data provide a likely mechanism for the complex bone phenotype of EGFR-/- mice, by suggesting that the IGF1R/mTOR-pathway is down-regulated through the EGFR, and that this process is necessary for maintaining an adequate equilibrium between osteoblast proliferation and differentiation.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersArbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftMedizinische Universität Wien, Diss., 2018(VLID)346243

More evidence needed before lower dialysate sodium concentrations can be recommended.

Reading the special report from Weiner et al1 advocating a “volume first” approach for improving clinical outcomes among hemodialysis patients was a pleasure. However, we disagree with the part of this proposal that dialysate sodium concentrations (DNa) should be “set routinely in the range of 134-138 mEq/L.”1(p685

Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease

Improved understanding of sex and gender-specific differences in the aetiology, mechanisms and epidemiology of chronic kidney disease (CKD) could help nephrologists better address the needs of their patients. Population-based studies indicate that CKD epidemiology differs by sex, affecting more women than men, especially with regard to stage G3 CKD. The effects of longer life expectancy on the natural decline of glomerular filtration rate (GFR) with age, as well as potential overdiagnosis of CKD through the inappropriate use of GFR equations, might be in part responsible for the greater prevalence of CKD in women. Somewhat paradoxically, there seems to be a preponderance of men among patients starting renal replacement therapy (RRT); the protective effects of oestrogens in women and/or the damaging effects of testosterone, together with unhealthier lifestyles, might cause kidney function to decline faster in men than in women. Additionally, elderly women seem to be more inclined to choose conservative care instead of RRT. Dissimilarities between the sexes are also apparent in the outcomes of CKD. In patients with predialysis CKD, mortality is higher in men than women; however, this difference disappears for patients on RRT. Although access to living donor kidneys among men and women seems equal, women have reduced access to deceased donor transplantation. Lastly, health-related quality of life while on RRT is poorer in women than men, and women report a higher burden of symptoms. These findings provide insights into differences in the underlying pathophysiology of disease as well as societal factors that can be addressed to reduce disparities in access to care and outcomes for patients with CK

Day-to-day variability in euvolemic body mass

AbstractShort-term variability in body mass is a common, everyday phenomenon; however, data on body mass variability are scarce. While the physiological variability of body mass is negligible in healthy individuals, it could have implications for therapy in patients with impaired volume homeostasis, for example, patients with kidney failure undergoing kidney replacement therapy. We analyzed a long-term dataset comprising 9521 days of standardized body mass measurements from one healthy male individual and assessed the variability in body mass as a positive or negative relative difference in body mass measured on subsequent days. The average and median relative differences were zero, with a standard deviation (SD) of 0.53% for the one-day interval, increasing to 0.69% for the 7-day interval, and this variability was constant throughout the observation period. A body mass variability of approximately 0.6% (±450 mL in a 75-kg patient) should be taken into consideration when weight-dependent treatment prescriptions, e.g. the ultrafiltration rates in patients on hemodialysis, are being set. Consequently, a “soft target weight”, considering the longitudinal variation of volume markers, such as body mass, might improve treatment quality