Small and Middle Molecular Weight Solute Clearance in Nocturnal Intermittent Peritoneal Dialysis

1999 ◽  
Vol 19 (6) ◽  
pp. 534-539 ◽  
Author(s):  
Donald F. Brophy ◽  
Kevin M. Sowinski ◽  
Michael A. Kraus ◽  
Sharon M. Moe ◽  
James E. Klaunig ◽  
...  

Objectives To determine the dialysate-to-plasma (D/P) concentration ratios and peritoneal dialytic clearance (ClD) of substances with a wide range of molecular weights in subjects receiving a simulated nocturnal intermittent peritoneal dialysis (NIPD) session. Design Open-label single-dose study. Subjects Six end-stage renal disease patients undergoing peritoneal dialysis (PD). Setting Clinical research center of a university-affiliated hospital. Interventions Subjects received intravenous gentamicin and vancomycin on the first day of the study. Subjects received no PD until their return on the following day, when subjects underwent a simulated NIPD session utilizing four 2- to 2.5-L peritoneal dialysate dwells of 2 hours. Blood and dialysate samples were collected immediately before the session and after each dialysate dwell for determination of urea, creatinine, gentamicin, vancomycin, and β2-microglobulin (β2M) concentrations. Each solute's D/P concentration ratio and peritoneal ClD were calculated. Measurements and Main Results The (mean ±SD) 2-hour D/P concentration ratios were 0.78 ± 0.05 (urea), 0.49 ± 0.11 (creatinine), 0.38 ± 0.08 (gentamicin), 0.11 ± 0.06 (vancomycin), and 0.07 ± 0.03 (β2M). Peritoneal ClD values (mL/min of dialysis) were 19.0 ± 2.8 (urea), 12.1 ± 3.5 (creatinine), 8.4 ± 2.8 (gentamicin), 2.7 ± 1.5 (vancomycin), and 1.7 ± 0.8 (β2M). The D/P concentration ratios and peritoneal ClD values for urea, creatinine, and gentamicin were significantly different from vancomycin and β2M (repeated measures ANOVA, p < 0.05). β2-Micro-globulin peritoneal ClD was strongly related to gentamicin peritoneal ClD ( r = 0.96, p < 0.05). Conclusion Small molecular weight solutes have significantly greater D/P and peritoneal ClD than middle molecular weight solutes in NIPD. In NIPD, daily peritoneal ClD of β2M is lower than that reported in continuous ambulatory PD. NIPD also results in lower drug ClD than that reported in continuous ambulatory PD studies.

1989 ◽  
Vol 9 (4) ◽  
pp. 267-272 ◽  
Author(s):  
J. Passlick ◽  
R. Wonner ◽  
E. Keller ◽  
L. Essers ◽  
B. Grabensee

To evaluate the pharmacokinetics of ofloxacin, a novel quinolon antibiotic, in patients with end-stage renal disease (ESRO) on continuous ambulatory peritoneal dialysis (CAPO), we investigated 6 patients in a single-dose study and 9 patients in a multiple-dose study, all without peritonitis. In the single-dose study, patients received 200 mg ofloxacin orally. Serum concentrations (Cmax) peaked at 3.1 ± 0.3 mg/L (x ± SEM), 1.6 ± 0.5 h after p. 0. administration of the drug. Elimination half-life ( t112) was 26.8 ± 2.5 h. Peritoneal clearance accounted for 10% of the total body clearance. After 5- h dwell time, ofloxacin concentrations in the dialysate were 1.5 ± 0.2 mg/L, which is above the MIC90 for most bacteria responsible for peritonitis in patients on CAPO. In the multiple dose study, 200 mg ofloxacin were administered twice, with a time interval of 12 h, followed by 200 mg for 9 days every morning. Mean trough serum levels were 2.6 ± 1.0 mg/L, mean peak concentrations were 4.1 ± 1.7 mg/L. Mean ofloxacin concentrations in the peritoneal effluent were 1.9 ± 0.9 mg/L. It is concluded that an oral loading dose of 400 mg on the first day and a maintenance dose of 200 mg ofloxacin/day does not lead to significant accumulation, even though the elimination by the peritoneal route is only small. The proposed dosing regimen could be an adequate therapy of peritonitis and exit-site infections in patients on CAPO since levels reached in the dialysate effluent are bactericidal. The clinical usefulness in the treatment of peritonitis has to be proven in further studies.


1985 ◽  
Vol 55 ◽  
Author(s):  
Zbylut J. Twardowski ◽  
Karl D. Nolph ◽  
Ramesh Khanna ◽  
Hannelore Hain ◽  
Harold Moore ◽  
...  

ABSTRACTA sustained ultrafiltration during long-dwell peritoneal dialysis exchanges cannot be achieved with rapidly absorbable small molecular weight substances such as commonly used glucose. Uncharged polymeric substances are absorbed slower, but yield insufficient osmotic driving force because osmolality is inversely proportional to the molecular weight.Charged polymers induce colloid osmotic pressure not only because of the molecules themselves, but also by ions kept in the peritoneal cavity by opposite charges of polymers. In anin vitromodel of peritoneal dialysis, a sustained ultrafiltration has been achieved with several synthetic polymers including polyacrylate, dextran sulfate and polyethylenimine. However, these polymers were locally toxic to the peritoneal membrane when tested in rats and rabbits.Chemically modified gelatin derivatives, such as polygelin, exypolygelatin, and succinylated gelatin are widely used in Europe as plasma substitutes. They are metabolized and have proven to be systemically non-toxic. These gelatin derivative solutions were tested in rat models of peritoneal dialysis. Up to 10% solutions achieved sustained ultrafiltration at the rate proportional to the concentration and no untoward systemic or local effects on the peritoneum were observed. Absorption of gelatin molecules ranged from 40–60% of the infused amounts. The results of the studies indicate that gelatin derivitives have potential for clinical use as osmotic agents in long-dwell peritoneal dialysis exchanges if the absorption rates in humans are markedly lower than in rats.


2018 ◽  
Vol 34 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Winnie Y. Sohn ◽  
Anthony A. Portale ◽  
Isidro B. Salusky ◽  
Hao Zhang ◽  
Lucy L. Yan ◽  
...  

Abstract Background Calcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects. Methods In this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing. Results Median plasma cinacalcet t max was 1 h (range 0.5–4.0 h); mean (SD) C max and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t 1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12–72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults. Conclusions In conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged < 6 years.


1993 ◽  
Vol 85 (4) ◽  
pp. 495-500 ◽  
Author(s):  
Chandra D. Mistry ◽  
Ram Gokal

1. In peritoneal dialysis the removal of excess body water (ultrafiltration) is traditionally achieved by means of dialysis solution made hypertonic to plasma by the addition of an osmotic agent. In vitro, the osmotic flow may be directed against the osmolality gradient by using a hypo-osmolar solution, but this phenomenon has not previously been applied to clinical peritoneal dialysis. 2. The ultrafiltration performances of hypo-osmolar dialysis solutions containing a high-molecular-weight glucose polymer (weight average molecular weight 22 000), isolated by fractionation of hydrolysed corn starch, were compared with those of hypertonic glucose solutions over a 12 h exchange in 11 patients well established on continuous ambulatory peritoneal dialysis. 3. Five per cent (272 +1.1 mosmol/kg) and 7.5% (277 + 2.0 mosmol/kg) glucose polymer solutions produced net ultrafiltration of 243 +53 and 526 +59 ml that were significantly greater than the ultrafiltration of −48 +96 and 223 +84 ml associated with 1.36% (339 +1.9 mosmol/kg) and 2.27% (393 +3.2 mosmol/kg) glucose solutions, respectively. The net ultrafiltration with 10% glucose polymer (284 +2.0 mosmol/kg) and 3.86% glucose (482 + 1.6 mosmol/kg) solutions were similar (699 +48 versus 708 +82 ml). 4. The transperitoneal absorption of glucose polymer was substantially lower than that of glucose solutions as was the potential calorie load per millilitre of ultrafiltrate. 5. The addition of 0.35% glucose (molecular weight 180) to 7.5% glucose polymer solution raised the dialysate osmolality to an iso-osmolar level (299 +0.8 mosmol/kg) and produced ultrafiltration which was 29% greater than with 7.5% glucose polymer solution alone. 6. The demonstration of ultrafiltration with hypo-osmolar dialysate represents an important advance towards the formulation of a physiological iso-osmolar dialysis solution, which may have long-term benefits over the conventional hypertonic solutions. The iso-osmolar combination of ‘colloid’ and ‘crystalloid’ osmotic agents looks promising with a potential for a wide range of ultrafiltration capabilities as well as metabolic correction.


1998 ◽  
Vol 18 (2) ◽  
pp. 210-216 ◽  
Author(s):  
Michael R. Jones ◽  
Todd W. Gehr ◽  
John M. Burkart ◽  
Richard J. Hamburger ◽  
Alfred P. Kraus ◽  
...  

Objective Losses of nutrients into dialysate may contribute to malnutrition. Peritoneal dialysis (PD) patients are reported to lose 3 -4 g/day of amino acids (AAs) and 4 -15 g/day of proteins. The extent to which one exchange with a 1.1% AA dialysis solution (Nutrineal, Baxter, Deerfield, IL, U.s.A.) offsets these losses was investigated in a 3-day inpatient study in 20 PD patients. Design Simple, open-label, cross-over study on consecutive days in a clinical research unit. On day 1 all patients were given a peritoneal equilibration test (PET). On day 2 they received 1.5% dextrose Dianeal (Baxter) as the first exchange of the day and their usual regimen thereafter. On day 3, the first exchange of the day was the 1.1% AA solution in place of 1.5% Dianeal and the usual PD regimen thereafter. On days 2 and 3 all dialysate effluent was collected and analyzed for AAs and proteins. Patients were maintained on a constant diet. Results Losses of AAs and total proteins on day 2 were 3.4 ± 0.9 g and 5.8 ± 2.4 g, respectively, totaling 9.2 ± 2.7 g. The net uptake of AAs on day 3 was 17.6 ± 2.6 g (80 ± 12% of the 22 g infused). Mean gains of AAs on day 3 exceeded losses of proteins and AAs on day 2, p < 0.001. Losses of total proteins, but not losses of AAs, and the net absorption of AAs from the dialysis solution were correlated directly with peritoneal membrane transport characteristics, obtained from the PET. Conclusion Daily losses of AAs and proteins into dialysate are more than offset by gains of AAs absorbed from one exchange with 1.1% AA-based dialysis solution. Net gains of AAs exceeded losses of proteins and AAs in all patients studied. The difference was relatively constant across a wide range of membrane transport types. Net AA gains were approximately two times the total AA and protein losses.


1968 ◽  
Vol 48 (2) ◽  
pp. 435-453
Author(s):  
FOTIS C. KAFATOS

1. The labial gland of adult saturniids produces a voluminous liquid at about the time of ecdysis, in response to either confinement of the moth or physostigmine injection. This liquid normally facilitates escape from the cocoon. 2. During secretion the gland accumulates K+ and HCO3- from the blood, and Rb+ if it is available, but excludes rather efficiently Na+, Li+, Sr2+, Ca2+, Mg2+, phosphate and other small molecular weight components of blood. Cl- is approximately equally distributed in blood and secretion. 3. The pH of the secretion is approximately 8.5, as compared with 6.5 for blood. 4. The secretion is in osmotic equilibrium with blood, even after alteration of blood osmotic pressure by injection of hypertonic or hypotonic solutions. 5. For both Cl- and Na+ the rate of entry into the secretion is proportional to concentration in blood; i.e. the efficiency of exclusion is characteristic for each ion, within a wide range of blood concentrations. 6. Secretion is accompanied by a potential difference across the secretory cell (ca.+25 mV. lumen positive). Secretion is abolished by dinitrophenol, but not by ouabain or acetazoleimide. 7. The results are best explained in terms of a respiration-mediated active accumulation of blood K+, in exchange for H+, in the basal region of the cells; this is presumably followed by release of the K+ into the lumen, with concomitant reabsorption of H+ from the secretion. The alkaline secretion then traps blood CO2 by converting it to HCO3-. Water follows osmotically, and other ions enter passively, at a rate determined by the corresponding permeability of the cells.


2014 ◽  
Vol 2 (8) ◽  
pp. 44
Author(s):  
Paula McKenzie ◽  
David Sotello ◽  
Kunal Parekh ◽  
Kristen Fuhrmann ◽  
Richard Winn

We report a 23-year-old woman with systemic lupus erythematous, lupus nephritis(class IV), and end-stage renal disease on peritoneal dialysis who presented with abdominal pain, nausea, vomiting, and diarrhea for one week. A previous admission for peritonitis occurred one month earlier, and peritoneal fluid culture at that time was negative. She was discharged on three weeks of intraperitoneal cefepime and vancomycin. On the current admission, due to recurrent symptoms approximately two weeks after her antibiotics were discontinued, peritoneal fluid cultures were positive for Mycobacterium fortuitum. The peritoneal catheter was removed, and trimethoprim- sulfamethoxazoleand ciprofloxacin were initially recommended for six months. This was later changed to trimethoprim-sulfamethoxazole and amikacin based on new susceptibilities.M. fortuitum is a rapidly growing mycobacterial species (RGM) widely distributedin nature; tap water is the major reservoir. It can produce a wide range of infections inhumans, and outbreaks have been reported in hospitals from contaminated equipment. Immunosuppression and chronic lung disease have been described as predisposing factors for RGM infection. Peritoneal dialysis associated with M. fortuitum infection occurs very rarely; no guidelines exist for treatment recommendations.


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