Dose-Response Relationship of Phloretin Therapy on Water and Glucose Transport during Experimental Peritoneal Dialysis.

Background: Water retention, ultrafiltration insufficiency, and metabolic complications due to abnormally high glucose concentrations are still common problems in patients treated with peritoneal dialysis. Phloretin, a nonselective inhibitor of facilitative glucose transporter channels (GLUT), has shown to improve water transport and lower glucose absorption in experimental peritoneal dialysis. However, the dose-response relationship remains unknown, and we therefore performed a dose-response study to elucidate the pharmacodynamic properties of intra-peritoneal phloretin therapy.

Transcellular transport of F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis.

Background: Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved.

Pulsed peritoneal dialysis in an experimental rat model: A first experience.

Background: Peritoneal dialysis (PD) is commonly performed using either intermittent or tidal exchanges, whereas other exchange techniques such as continuous flow PD are little used. Previous research indicated that stirring the intra-peritoneal dialysate markedly increases small solute clearances. Here, we tested the hypothesis that stirring of the dialysate increases small solute clearances by using a novel exchange technique where the dialysate is pulsed back and forth during the treatment without addition of fresh fluid.

Relationship between fill volume and transport in peritoneal dialysis-from bench to bedside.

Introduction: Larger fill volumes in peritoneal dialysis (PD) typically improve small solute clearance and water removal, and -but the relationship between intraperitoneal volume and the capacities for solute and water transport in PD has been little studied. Here, it is proposed that this relative relationship is described by a simple ratio (Volume/Volume) up to a critical break-point volume, beyond which further volume increase is less beneficial in terms of solute and water removal.

Method: To scrutinize this hypothesis, experiments were conducted in a rat model of PD alongside a retrospective analysis of data from a prior clinical study.

Determining the residual volume in peritoneal dialysis using low molecular weight markers.

Background: Variation in residual volume between peritoneal dialysis dwells creates uncertainty in ultrafiltration determination, dialysis efficiency, and poses a risk of overfill if the residual volume is large. Measuring the dilution of a marker molecule during fluid fill offers a convenient approach, however, estimation accuracy depends on the choice of dilution marker. We here evaluate the feasibility of creatinine and urea as dilution markers compared to albumin-based residual volumes and three-pore model estimations.

Quantifying Ultrafiltration in Peritoneal Dialysis Using the Sodium Dip.

Key Points: Ultrafiltration (UF) is a key component of clinical peritoneal dialysis prescription, but the traditional method to assess UF is hampered by large inaccuracies. Here we propose a novel method, based on a computational model and on a single dialysate sodium measurement, to accurately estimate UF and osmotic conductance to glucose in patients on peritoneal dialysis.

Background: Volume overload is highly prevalent among patients treated with peritoneal dialysis (PD), contributes to hypertension, and is associated with an increased risk of cardiovascular events and death in this population.

Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes.

Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes.

Methods: In a cohort study, 63 patients undergoing LD ( = 26) and DD ( = 37) transplantation were prospectively included.

Experimental hemodialysis in diet-induced ketosis and the potential use of dialysis as an adjuvant cancer treatment.

Numerous in vivo studies on the ketogenic diet, a diet that can induce metabolic conditions resembling those following extended starvation, demonstrate strong outcomes on cancer survival, particularly when combined with chemo-, radio- or immunological treatments. However, the therapeutic application of ketogenic diets requires strict dietary adherence from well-informed and motivated patients, and it has recently been proposed that hemodialysis might be utilized to boost ketosis and further destabilize the environment for cancer cells. Yet, plasma ketones may be lost in the dialysate-lowering blood ketone levels.

The Peritoneal Membrane and Its Role in Peritoneal Dialysis.

A healthy and functional peritoneal membrane is key to achieving sufficient ultrafiltration and restoring fluid balance, a major component of high-quality prescription in patients treated with peritoneal dialysis (PD). Variability in membrane function at the start of PD or changes over time on treatment influence dialysis prescription and outcomes, and dysfunction of the peritoneal membrane contributes to fluid overload and associated complications. In this review, we summarize the current knowledge about the structure, function, and pathophysiology of the peritoneal membrane with a focus on clinical implications for patient-centered care.

Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats.

Background: Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis (PD). We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during PD in rats. However, more recently, we found that phlorizin, a dual blocker of sodium glucose cotransporters 1 and 2, reduces glucose diffusion in PD.

Dual SGLT1/SGLT2 inhibitor phlorizin reduces glucose transport in experimental peritoneal dialysis.

Introduction: Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD.

Optimised versus standard automated peritoneal dialysis regimens pilot study (OptiStAR): A randomised controlled crossover trial.

Background: The continuous global rise of end-stage kidney disease creates a growing demand of economically beneficial home-based kidney replacement therapies such as peritoneal dialysis (PD). However, undesirable absorption and exposure of peritoneal tissues to glucose remain major limitations of PD.

Methods: We compared a reference (standard) automated PD regimen 6 × 2 L 1.

High versus low ultrafiltration rates during experimental peritoneal dialysis in rats: Acute effects on plasma volume and systemic haemodynamics.

Introduction: Intradialytic hypotension is a common complication of haemodialysis, but uncommon in peritoneal dialysis (PD). This may be due to lower ultrafiltration rates in PD compared to haemodialysis, allowing for sufficient refilling of the blood plasma compartment from the interstitial volume, but the underlying mechanisms are unknown. Here we assessed plasma volume and hemodynamic alterations during experimental PD with high versus low ultrafiltration rates.

Potential relationship between eGFR /eGFR -ratio and glomerular basement membrane thickness in diabetic kidney disease.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomerular basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle-molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine.

Clemizole and La salts ameliorate angiotensin II-induced glomerular hyperpermeability in vivo.

Angiotensin II (Ang II) induces marked, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor, Ang II elicits Ca influx into cells, mediated by TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6). Clemizole and La salts have been shown to block TRPC channels in vitro, and we therefore tested their potential effect on Ang II-induced glomerular hyperpermeability.

Optimization of bimodal automated peritoneal dialysis prescription using the three-pore model.

Background: Previous studies suggested that automated peritoneal dialysis (APD) could be improved in terms of shorter treatment times and lower glucose absorption using bimodal treatment regimens, having 'ultrafiltration (UF) cycles' using a high glucose concentration and 'clearance cycles' using low or no glucose. The purpose of this study is to explore such regimes further using mathematical optimization techniques based on the three-pore model.

Methods: A linear model with constraints is applied to find the shortest possible treatment time given a set of clinical treatment goals.

SGLT2 inhibition does not reduce glucose absorption during experimental peritoneal dialysis.

Introduction: Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may also occur via intracellular or trans-cellular pathways.

Methods: We performed PD in anesthetized Sprague-Dawley rats using a fill volume of 20 mL with either 1.

Novel Method for Osmotic Conductance to Glucose in Peritoneal Dialysis.

Introduction: The osmotic conductance to glucose (OCG) is a crucial determinant of ultrafiltration (UF) in peritoneal dialysis (PD) patients and can be used to monitor membrane integrity in patients on long-term PD. It has been proposed that OCG can be assessed based on drained volumes in 2 consecutive 1-hour glucose dwells, usually 1.5% and 4.

Optimized vs. Standard Automated Peritoneal Dialysis Regimens (OptiStAR): study protocol for a randomized controlled crossover trial.

Background: It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having "UF cycles" using a higher glucose concentration, and "Clearance cycles" using a low concentration or, preferentially, no glucose.

Albumin infusion rate and plasma volume expansion: a randomized clinical trial in postoperative patients after major surgery.

Background: Optimal infusion rate of colloids in patients with suspected hypovolemia is unknown, and the primary objective of the present study was to test if plasma volume expansion by 5% albumin is greater if fluid is administered slowly rather than rapidly.

Methods: Patients with signs of hypoperfusion after major abdominal surgery were randomized to intravenous infusion of 5% albumin at a dose of 10 ml/kg (ideal body weight) either rapidly (30 min) or slowly (180 min). Plasma volume was measured using radiolabeled albumin at baseline, at 30 min, and at 180 min after the start of infusion.

Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ET receptor.

Emerging evidence indicates that endogenous production of endothelin (ET)-1, a 21-amino acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are, however, currently not known.

Computer Simulations of Continuous Flow Peritoneal Dialysis Using the 3-Pore Model-A First Experience.

Continuous flow peritoneal dialysis (CFPD) is performed using a continuous flux of dialysis fluid via double or dual-lumen PD catheters, allowing a higher dialysate flow rate (DFR) than conventional treatments. While small clinical studies have revealed greatly improved clearances using CFPD, the inability to predict ultrafiltration (UF) may confer a risk of potentially harmful overfill. Here we performed physiological studies of CFPD using the extended 3-pore model.