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American Journal of Physiology. Renal... Nov 2016For patients with end-stage kidney disease unable to receive a kidney transplant, replacement of kidney function with dialysis is necessary to extend life. Peritoneal...
For patients with end-stage kidney disease unable to receive a kidney transplant, replacement of kidney function with dialysis is necessary to extend life. Peritoneal dialysis (PD) and hemodialysis (HD) are the two major forms of dialysis therapy. HD involves the passage of blood via an extracorporeal circuit whereby removal of small solutes, toxins, and water is achieved across a synthetic, semipermeable dialysis membrane. In contrast, in PD, the dialysis membrane is the highly vascularized internal lining of the peritoneal cavity. Intraperitoneal installation of hypertonic high glucose PD solution creates a transmembrane osmotic and diffusive gradient that facilitates water removal [ultrafiltration (UF)], convection, and diffusion of uremic toxins. Insight into the physiology of solute and water transport across the peritoneal membrane has been enhanced by the proposal of the ''three-pore model'' of peritoneal membrane transport. Transport characteristics and UF capacity of the peritoneal membrane vary among individuals, and deleterious changes in the membrane may ensue over time. The degree to which these changes are a direct consequence of the type and composition of currently available PD solutions, recurrent infectious episodes, genetic differences among individuals, or a combination thereof is the subject of intense study. Adverse consequences resulting from the systemic and local metabolic effects of intraperitoneal glucose exposure, infection of the PD fluid, PD catheter dysfunction, and patient burnout from self-care often limit the long-term success of the therapy. Research aimed at addressing these challenges will examine the use of more biocompatible PD solutions and strategies aimed at attenuating progressive peritoneal membrane injury.
Topics: Dialysis Solutions; Humans; Kidney Failure, Chronic; Peritoneal Dialysis
PubMed: 27009336
DOI: 10.1152/ajprenal.00012.2016 -
BMC Nephrology Feb 2022Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the phase 3b DIALIZE study, we examined the spectrum of potassium responses to SZC.
METHODS
Post-hoc analyses with SZC and placebo included: the number of long interdialytic interval (LIDI) visits during the 4-week evaluation period where patients attained pre-dialysis serum potassium (sK) concentrations of 4.0-5.0 and 4.0-5.5 mmol/L; potassium gradient (the difference between pre-dialysis sK and dialysate potassium) at days 36, 43, 50, and 57, and change from baseline to the end of treatment (EOT) using categories of potassium gradient (1 to < 2, 2 to < 3, 3 to < 4, and ≥ 4 mmol/L).
RESULTS
A greater proportion of patients achieved the ranges of pre-dialysis sK concentration with SZC versus placebo for ≥1, ≥ 2, ≥ 3, and 4 LIDI visits over 4 weeks; 23.7 and 48.5% of patients in the SZC group achieved pre-dialysis sK concentrations of 4.0-5.0 and 4.0-5.5 mmol/L, respectively, at all 4 LIDI visits. Baseline mean potassium gradient was similar with SZC and placebo. At day 57, mean (standard deviation) potassium gradient was 2.78 (0.08) mmol/L with SZC and 3.52 (0.08) mmol/L with placebo; mean difference (95% confidence interval) was - 0.74 mmol/L (- 0.97 to - 0.52). A greater reduction in potassium gradient category from baseline towards lower-risk categories at EOT was observed with SZC versus placebo.
CONCLUSIONS
These analyses expand our knowledge of the spectrum of potassium responses with SZC in hyperkalemic hemodialysis patients.
TRIAL REGISTRATION
NCT03303521 .
Topics: Dialysis Solutions; Double-Blind Method; Female; Humans; Hyperkalemia; Ion Exchange Resins; Kidney Failure, Chronic; Male; Middle Aged; Potassium; Renal Dialysis; Silicates
PubMed: 35135481
DOI: 10.1186/s12882-021-02569-7 -
Journal of the American Society of... Jul 2018Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies...
Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. modeling and studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone. These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.
Topics: Animals; Aquaporin 1; Biological Transport; Colloids; Computer Simulation; Crystalloid Solutions; Dialysis Solutions; Genotype; Glucose; Icodextrin; Mice; Models, Theoretical; Osmosis; Peritoneal Dialysis; Peritoneum; Water
PubMed: 29844208
DOI: 10.1681/ASN.2017080828 -
Blood Purification 2023Hyperammonemia is a life-threatening condition mainly due to the neurotoxicity of ammonia. Ammonia scavengers may be insufficient, and extracorporeal treatment may be... (Review)
Review
Hyperammonemia is a life-threatening condition mainly due to the neurotoxicity of ammonia. Ammonia scavengers may be insufficient, and extracorporeal treatment may be required. Continuous treatments are preferred, and a high-dose continuous renal replacement therapy (CRRT) must be prescribed to ensure a fast ammonia depletion. Many of the children with hyperammonemia are newborns, with lower blood volume than older children. The majority of the CRRT systems are adult-based, with large extracorporeal priming volumes and inadequate UF control. Recent strides have been made in the development of CRRT systems more suitable for young children with smaller sets to use in adult machines and dedicated monitors for neonates and infants. The main advantage of the machines for adults is the higher dialysis fluid flows, however with greater hemodynamic risks. Pediatric monitors have been designed to reduce the extracorporeal volume and to increase the precision of the treatment. However, they have substantial limitation in clearance performances. In this review, we discuss on current strategies to provide CRRT in newborns and small infants with hyperammonemia. We also presented our experience with the use of CARPEDIEM™ implemented in a CVVHDF modality, boosting the diffusive clearance with a post-replacement convective mechanism.
Topics: Infant, Newborn; Infant; Humans; Child; Adolescent; Child, Preschool; Renal Replacement Therapy; Hyperammonemia; Ammonia; Continuous Renal Replacement Therapy; Dialysis Solutions; Acute Kidney Injury
PubMed: 37725911
DOI: 10.1159/000533486 -
International Journal of Molecular... Nov 2021Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of... (Review)
Review
Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.
Topics: Animals; Dialysis Solutions; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Peritoneum; Sodium
PubMed: 34884617
DOI: 10.3390/ijms222312804 -
Cancer Chemotherapy and Pharmacology Apr 2023For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and...
PURPOSE
For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from poly(ADP-ribose) polymerase inhibitor (PARPi) therapy. Here we report the pharmacokinetics (PK), efficacy, safety and tolerability of olaparib capsules 200 mg BID in a patient with recurrent epithelial ovarian cancer (EOC) and ESRD requiring hemodialysis.
METHODS
Blood and dialysate samples of the patient were collected on a dialysis and non-dialysis day. Olaparib total plasma concentrations were determined through high-performance liquid chromatography with tandem mass spectrometric detection. Actual scheduled sample times were used in the PK analysis to determine multiple dose PK parameters at steady state.
RESULTS
Maximum concentration was achieved 1.5 h after drug administration on non- dialysis and after 1 h on dialysis day. The steady-state trough concentration and the maximal plasma concentration were similar on dialysis and non- dialysis day. On non-dialysis day, the AUC was 30% higher (24.0 µg.h/mL vs. 16.9 µg.h/ml) than on dialysis day. The plasma clearance CL/F was lower on non-dialysis day. Olaparib was not detectable in the dialysate samples.
CONCLUSION
A total dose of olaparib 200 mg BID capsule formulation was well tolerated by our patient with ESRD and hemodialysis. Moreover, this maintenance therapy led to 16 months of progression free survival. Further trials on PARPi therapy in patients with hemodialysis are warranted.
Topics: Humans; Female; Neoplasm Recurrence, Local; Ovarian Neoplasms; Antineoplastic Agents; Kidney Failure, Chronic; Renal Dialysis; Poly(ADP-ribose) Polymerase Inhibitors; Dialysis Solutions; Phthalazines
PubMed: 36947209
DOI: 10.1007/s00280-023-04514-x -
Toxins Feb 2021Peritoneal dialysis (PD) is a feasible and effective renal replacement therapy (RRT) thanks to the dialytic properties of the peritoneal membrane (PM). Preservation of...
Peritoneal dialysis (PD) is a feasible and effective renal replacement therapy (RRT) thanks to the dialytic properties of the peritoneal membrane (PM). Preservation of PM integrity and transport function is the key to the success of PD therapy, particularly in the long term, since the prolonged exposure to unphysiological hypertonic glucose-based PD solutions in current use is detrimental to the PM, with progressive loss of peritoneal ultrafiltration capacity causing technique failure. Moreover, absorbing too much glucose intraperitoneally from the dialysate may give rise to a number of systemic metabolic effects. Here we report the preliminary results of the first clinical experience based on the use in continuous ambulatory PD (CAPD) patients of novel PD solutions obtained through partly replacing the glucose load with other osmotically active metabolites, such as L-carnitine and xylitol. Ten CAPD patients were treated for four weeks with the new solutions. There was good tolerance to the experimental PD solutions, and no adverse safety signals were observed. Parameters of dialysis efficiency including creatinine clearance and urea Kt/V proved to be stable as well as fluid status, diuresis, and total peritoneal ultrafiltration. The promising tolerance and local/systemic advantages of using L-carnitine and xylitol in the PD solution merit further research.
Topics: Adult; Aged; Carnitine; Dialysis Solutions; Female; Glucose; Humans; Italy; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies; Time Factors; Treatment Outcome; Xylitol
PubMed: 33668249
DOI: 10.3390/toxins13030174 -
Peritoneal Dialysis International :... Mar 2023Computerised tomographic (CT) peritoneography is performed on peritoneal dialysis (PD) patients to identify peritoneal boundary defects, dialysate maldistributions and...
BACKGROUND
Computerised tomographic (CT) peritoneography is performed on peritoneal dialysis (PD) patients to identify peritoneal boundary defects, dialysate maldistributions and loculated fluid collections. Iodinated contrast media are added to dialysate and infused through the dialysis catheter, and CT images are obtained. Chemical compatibility of contrast media with dialysis solutions has not been studied. In some institutions, pharmacists charged with oversight of compounded sterile preparations have placed a moratorium on the use of contrast media-dialysate mixtures until compatibility data become available. This study was undertaken to examine the compatibility of non-ionic iodinated contrast agents added to PD solution for the performance of CT peritoneography.
METHODS
100 mL of three non-ionic iodinated contrast agents, iopamidol 370 mgI/mL, iohexol 300 mgI/mL and iodixanol 320 mgI/mL, were mixed with 2 L 1.5% dextrose PD solution and stored at 2-8°C, 25°C and 40°C. Observations at predefined intervals were made over 5 days for visual appearance, turbidity, pH, drug concentration and chemical degradation.
RESULTS
Iopamidol, iohexol and iodixanol were stable for 5 days under study conditions. The contrast-dialysate mixture remained clear and colourless, no turbidity changes observed, pH and drug concentrations were stable and no increase in existing impurities or new impurities were detected.
CONCLUSIONS
The addition of commonly used non-ionic iodinated contrast agents to 1.5% dextrose dialysis solution is chemically stable, meeting the criteria set forth in the standards and guidelines of the US Pharmacopeia and the Institute of Safe Medication Practices. A protocol for performing CT peritoneography is recommended herein to facilitate patient safety and diagnostic reliability of the imaging study.
Topics: Humans; Peritoneal Dialysis; Contrast Media; Peritoneal Dialysis, Continuous Ambulatory; Iohexol; Iopamidol; Reproducibility of Results; Dialysis Solutions; Tomography, X-Ray Computed; Glucose
PubMed: 35505602
DOI: 10.1177/08968608221096562 -
Blood Purification 2015Many pieces of evidence of online hemodiafiltration (HDF) have been reported, and the clinical advantage of postdilution online HDF with sufficient substitution is now... (Review)
Review
Many pieces of evidence of online hemodiafiltration (HDF) have been reported, and the clinical advantage of postdilution online HDF with sufficient substitution is now established. After the approval of online HDF in 2012, the number of online HDF patients has been dramatically increasing in Japan and reached 10% of the total dialysis population at the end of 2013. One of the marked characteristics of Japanese online HDF is a widespread use of predilution treatment and, in 2013, 90.8% of online HDFs were carried out with the predilution mode. The main reason for the wide use of predilution online HDF results from the low blood flow rate in Japan, by which it is difficult to substitute a sufficient volume during the limited treatment time. Other reasons to choose the predilution mode include the reduction of albumin loss and the suppression of membrane fouling during treatment. Contrary to postdilution treatment, adequate clinical evidence has not been reported for predilution online HDF to provide a better outcome of the patients. A further clinical trial is expected to elucidate the clinical advantages over conventional hemodialysis for predilution online HDF.
Topics: Aged; Dialysis Solutions; Female; Hemodiafiltration; Humans; Japan; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged
PubMed: 26344508
DOI: 10.1159/000437405 -
Scientific Reports Apr 2023In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide...
In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide chains are degraded by α-amylase activity in dialysate, influencing its osmotic properties. We modelled water and solute removal taking into account degradation by α-amylase and absorption of icodextrin from the peritoneal cavity. Data from 16 h dwells with icodextrin-based solution in 11 patients (3 icodextrin-exposed, 8 icodextrin-naïve at the start of the study) on dialysate volume, dialysate concentrations of glucose, urea, creatinine and α-amylase, and dialysate and blood concentrations of seven molecular weight fractions of icodextrin were analysed. The three-pore model was extended to describe hydrolysis of icodextrin by α-amylase. The extended model accurately predicted kinetics of ultrafiltration, small solutes and icodextrin fractions in dialysate, indicating differences in degradation kinetics between icodextrin-naïve and icodextrin-exposed patients. In addition, the model provided information on the patterns of icodextrin degradation caused by α-amylase. Modelling of icodextrin kinetics using an extended three-pore model that takes into account absorption of icodextrin and changes in α-amylase activity in the dialysate provided accurate description of peritoneal transport and information on patterns of icodextrin hydrolysis during long icodextrin dwells.
Topics: Humans; Icodextrin; Hydrolysis; Kinetics; Glucans; Peritoneal Dialysis; Dialysis Solutions; Peritoneum; Glucose; alpha-Amylases; Ultrafiltration
PubMed: 37085652
DOI: 10.1038/s41598-023-33480-w