| 1. |
- Al-Hwiesh, AK, et al.
(författare)
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Metformin in peritoneal dialysis: a pilot experience
- 2014
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 34:4, s. 368-375
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Tidskriftsartikel (refereegranskat)abstract
- In a number of patients, the antidiabetic drug metformin has been associated with lactic acidosis. Despite the fact that diabetes mellitus is the most common cause of end-stage renal disease (ESRD) and that peritoneal dialysis (PD) is an expanding modality of treatment, little is known about optimal treatment strategies in the large group of PD patients with diabetes. In patients with ESRD, the use of metformin has been limited because of the perceived risk of lactic acidosis or severe hypoglycemia. However, metformin use is likely to be beneficial, and PD might itself be a safeguard against the alleged complications. Methods Our study involved 35 patients with insulin-dependent type 2 diabetes [median age: 54 years; interquartile range (IQR): 47–59 years] on automated PD (APD) therapy. Patients with additional risk factors for lactic acidosis were excluded. Metformin was introduced at a daily dose in the range 0.5 – 1.0 g. All patients were monitored for glycemic control by blood sugar levels and HbA1c. Plasma lactic acid levels were measured weekly for 4 weeks and then monthly to the end of the study. Plasma and effluent metformin and plasma lactate levels were measured simultaneously. Results In this cohort, the median duration of diabetes was 18 years (IQR: 14 – 21 years), median time on PD was 31 months (IQR: 27 – 36 months), and median HbA1c was 6.8% (IQR: 5.9% – 6.9%). At metformin introduction and at the end of the study, the median anion gap was 11 mmol/L (IQR: 9 – 16 mmol/L) and 12 mmol/L (IQR: 9 – 16 mmol/L; p > 0.05) respectively, median pH was 7.33 (IQR: 7.32 – 7.36) and 7.34 (IQR: 7.32 – 7.36, p > 0.05) respectively, and mean metformin concentration in plasma and peritoneal fluid was 2.57 ± 1.49 mg/L and 2.83 ± 1.7 mg/L respectively. In the group overall, mean lactate was 1.39 ± 0.61 mmol/L, and hyperlactemia (>2 mmol/L to 5 mmol/L) was found in 4 of 525 plasma samples (0.76%), but the patients presented no symptoms. None of the patients registered a plasma lactate level above 5 mmol/L. We observed no correlation between plasma metformin and plasma lactate ( r = 0.27). Conclusions Metformin may be used with caution in APD patients with insulin-dependent type 2 diabetes. Although our study demonstrated the feasibility of metformin use in APD, it was not large enough to demonstrate safety; a large-scale study is needed.
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| 2. |
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| 3. |
- Bazargani, Farhan, 1969, et al.
(författare)
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Low molecular weight heparin improves peritoneal ultrafiltration and blocks complement and coagulation.
- 2005
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : Multimed Inc.. - 0896-8608 .- 1718-4304. ; 25:4, s. 394-404
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell. DESIGN: Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations. RESULTS: Exposure to PD fluid induced activation of IP complement [formation of C3a (desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin-antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration. CONCLUSIONS: The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.
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| 4. |
- Bazargani, Farhan, 1969-, et al.
(författare)
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The roles of complement factor C5a and CINC-1 in glucose transport, ultrafiltration, and neutrophil recruitment during peritoneal dialysis
- 2006
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Ingår i: Peritoneal Dialysis International. - : Sage Publications. - 0896-8608 .- 1718-4304. ; 26:6, s. 688-696
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a recent experimental study, we showed that low molecular weight heparin improved ultrafiltration and blocked complement activation and coagulation in a single peritoneal dialysis (PD) dwell.Objective: The aim of the present study was to evaluate the possible contribution of the complement factor C5a and the potential interactions between C5a, the coagulation system, and cytokines of the interleukin (IL)-8 family (cytokine-induced neutrophil chemoattractant; CINC-1).Methods: Nonuremic rats were exposed through an in-dwelling catheter to a single dose of 20 mL glucose- (2.5%) based fifter-sterilized PD fluid, with or without the addition of anti-rat CS antibody. The dwell fluid was analyzed 2 and 4 hours later concerning activation of the coagulation cascades, neutrophil recruitment, ultrafiltration volume; CINC-1, glucose, urea, and histamine concentrations; and ex vivo intraperitoneal chemotactic activity. Results: The numbers of neutrophils and levels of thrombin-antithrombin complex (TAT) and CINC-1 increased significantly during the PD dwell. C5 blockade significantly reduced the levels of TAT and increased the ultrafiltration volumes at 2 hours. Glucose concentrations were significantly positively correlated to ultrafiltration volumes.Conclusions: Blockade of C5 Leads to an increase in ultrafiltration, probably by a mechanism that involves a reduction in glucose transport. This effect may form a basis for improving PD efficiency in situations where high glucose transport limits ultrafiltration. Mechanisms connected to complement activation during PD may involve coagulation. Further studies of the intraperitoneal cascade systems under conditions of PD are indicated.
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| 5. |
- Bergling, Karin, et al.
(författare)
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Optimised versus standard automated peritoneal dialysis regimens pilot study (OptiStAR) : A randomised controlled crossover trial
- 2022
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Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608. ; 42:6, s. 615-621
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Tidskriftsartikel (refereegranskat)abstract
- 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 1.36% glucose (76 mmol/L) over 9 h with a novel, theoretically glucose sparing (optimised) prescription consisting of ‘ultrafiltration cycles’ with high glucose strength (126 mmol/L) and ‘clearance cycles’ with ultra-low, physiological glucose (5 mmol/L) for approximately 40% of the treatment time. Twenty-one prevalent PD patients underwent the optimised regimen (7 × 2 L 2.27% glucose + 5 × 2 L 0.1% glucose over 8 h) and the standard regimen in a crossover fashion. Six patients were excluded from data analysis. Results: Median glucose absorption was 43 g (IQR 41–54) and 44 g (40–55) for the standard and optimised intervention, respectively (p = 1). Ultrafiltration volume, weekly Kt/V creatinine and urea were significantly improved during optimised interventions, while no difference in sodium removal was detected. Post hoc analysis showed significantly improved ultrafiltration efficiency (ml ultrafiltration per gram absorbed glucose) during optimised regimens. No adverse events were observed except one incidence of drain pain. Conclusion: Optimised treatments were feasible and well tolerated in this small pilot study. Despite no difference in absorbed glucose, results indicate possible improvements of ultrafiltration efficiency and small solute clearances by optimised regimens. Use of optimised prescriptions as glucose sparing strategy should be evaluated in larger study populations.
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| 6. |
- Braide, Magnus, 1955, et al.
(författare)
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Erythrocytes as Volume Markers in Experimental PD Show that Albumin Transport in the Extracellular Space Depends on PD Fluid Osmolarity
- 2016
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Ingår i: Peritoneal Dialysis International. - Toronto, Canada : SAGE Publications. - 0896-8608 .- 1718-4304. ; 36:3, s. 247-256
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Tidskriftsartikel (refereegranskat)abstract
- Background: Macromolecules, when used as intraperitoneal volume markers, have the disadvantage of leaking into the surrounding tissue. Therefore, Cr-51-labeled erythrocytes were evaluated as markers of intraperitoneal volume and used in combination with I-125-labeled bovine serum albumin to study albumin transport into peritoneal tissues in a rat model of peritoneal dialysis (PD). Methods: Single dwells of 20 mL of lactate-buffered filter-sterilized PD fluid at glucose concentrations of 0.5%, 2.5%, and 3.9% were performed for 1 or 4 hours. Tissue biopsies from abdominal muscle, diaphragm, liver, and intestine, and blood and dialysate samples, were analyzed for radioactivity. Results: The dialysate distribution volume of labeled erythrocytes, measured after correction for lymphatic clearance to blood, was strongly correlated with, but constantly 3.3 mL larger than, drained volumes. Erythrocyte activity of rinsed peritoneal tissue biopsies corresponded to only 1 mL of dialysate, supporting our utilization of erythrocytes as markers of intraperitoneal volume. The difference between the distribution volumes of albumin and erythrocytes was analyzed to represent the albumin loss into the peritoneal tissues, which increased rapidly during the first few minutes of the dwell and then leveled out at 2.5 mL. It resumed when osmotic ultrafiltration turned into reabsorption and, at the end of the dwell, it was significantly lower for the highest osmolarity PD fluid (3.9% glucose). Biopsy data showed the lowest albumin accumulation and edema formation in abdominal muscle for the 3.9% fluid. Conclusion: Labeled erythrocytes are acceptable markers of intraperitoneal volume and, combined with labeled albumin, provided novel kinetic data on albumin transport in peritoneal tissues.
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| 7. |
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| 8. |
- Cavallini, Nicola, 1978, et al.
(författare)
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Neuropeptide release augments serum albumin loss and reduces ultrafiltration in peritoneal dialysis
- 2012
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Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608 .- 1718-4304. ; 32:2, s. 168-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: The triggers of the acute local inflammatory response to peritoneal dialysis (PD) fluid exposure remain unknown. In the present study, we investigated the effects of neurogenic inflammation and mast cell degranulation on water and solute transport in experimental PD. Methods: Single 2-hour dwells in rats with PD catheters were studied. Histamine and the neuropeptides substance P and calcitonin gene-related peptide (CGRP) were measured in PD fluid samples by ELISA. Radiolabeled albumin (I-125 and I-131 respectively) was used as an intraperitoneal (IP) and intravascular tracer. Glucose and urea concentrations were measured in plasma and PD fluid. The effects of varying the volume and osmolarity of a lactate-buffered PD fluid were compared and related to the effects of pharmacologic intervention. Results: Application of 20 mL 3.9% glucose PD fluid induced an IP histamine release during the first 30 minutes, blockable by the mast cell stabilizer doxantrazole and the substance P neurokinin-1 receptor (NK1R)-blocker spantide. Histamine release was also inhibited at a reduced PD volume (14 mL), but was not affected by normalizing the PD fluid osmolarity. Blockade of NK1R also reduced plasma albumin leakage to the peritoneal cavity. Inhibition of CGRP receptors by CGRP8-37 improved osmotic (transcapillary) and net ultrafiltration and reduced the dialysate urea concentration. Neuropeptide release was not clearly related to activation of the TrpV1 receptor, the classic trigger of neurogenic inflammation. Conclusions: Neuropeptide release exaggerated albumin loss and reduced ultrafiltration in this rat PD model. Intervention aimed at the neuropeptide action substantially improved PD efficiency.
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| 9. |
- Chen, ZM, et al.
(författare)
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High alkaline phosphatase and low intact parathyroid hormone associate with worse clinical outcome in peritoneal dialysis patients
- 2021
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 41:2, s. 236-243
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Tidskriftsartikel (refereegranskat)abstract
- Alkaline phosphatase (ALP) is used as a biomarker to monitor the chronic kidney disease–mineral bone disorder (CKD-MBD) and high levels of parathyroid hormone (PTH) that were reported to be related to increased mortality in CKD patients. Therefore, we conducted this longitudinal cohort study to evaluate the relations between ALP and intact PTH (iPTH) and the associations with all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients.Methods:In 1276 incident PD patients (median age 50 years, 56% males), baseline serum ALP, iPTH, and metabolic biomarkers potentially linked to CKD-MBD were analyzed in relation to mortality during follow-up period of up to 60 months. All-cause and cardiovascular mortality risk of ALP and iPTH were analyzed with competing-risks regression models with transplantation as competing risk adjusting for all covariates.Results:After adjustments for confounders by logistic regression model, older age, higher change level to levels of iPTH, S-albumin, calcium, alanine transaminase (ALT), and lower level of phosphorus were associated with higher ALP level (>79 U/L), and female gender, non-diabetes mellitus, younger age, lower calcium, higher ALT, total bilirubin, phosphorus, and ALP were associated with higher iPTH level (>300 pg/mL). During 60 months (median 44 months) of follow-up, the all-cause mortality rate was 16%, and 91 (46%) of the 199 deaths were caused by cardiovascular disease. In competing-risks regression analysis, “high ALP + low iPTH” was independently associated with all-cause and cardiovascular mortality after adjustment for age, gender, presence of diabetes, and cardiovascular disease, the calendar year of recruitment and vitamin D therapy in PD patients. The subhazard ratio (sHR) of group “high ALP + low iPTH” was 1.96 times and 3.35 times higher than sHR of group “low ALP + high iPTH” for all-cause mortality and cardiovascular mortality, respectively.Conclusions:The combination of high ALP and low iPTH was independently associated with increased all-cause and cardiovascular mortality in PD patients, suggesting that ALP and iPTH have the potential to predict clinical outcomes and might be useful risk assessment tools in PD patients. Further studies exploring the observed association between combination of ALP with iPTH and mortality are warranted.
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| 10. |
- Corzo, L, et al.
(författare)
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Technique failure in remote patient monitoring program in patients undergoing automated peritoneal dialysis: A retrospective cohort study
- 2022
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 42:3, s. 288-296
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Tidskriftsartikel (refereegranskat)abstract
- Remote patient monitoring (RPM) programs in automated peritoneal dialysis (APD) allow clinical teams to be aware of many aspects and events of the therapy that occur in the home. The present study evaluated the association between RPM use and APD technique failure. Methods: A retrospective, multicentre, observational cohort study of 558 prevalent adult APD patients included between 1 October 2016 and 30 June 2017 with follow-up until 30 June 2018 at Renal Therapy Services network in Colombia. Patients were divided into two cohorts based on the RPM use: APD-RPM ( n = 148) and APD-without RPM ( n = 410). Sociodemographic and clinical characteristics of all patients were summarized descriptively. A propensity score was used to create a pseudo-population in which the baseline covariates were well balanced. The association of RPM with technique failure was estimated adjusting for the competing events death and kidney transplant. Results: Five hundred fifty-eight patients were analyzed. 26.5% had APD-RPM. In the matched sample comprising 148 APD-RPM and 148 APD-without RPM patients, we observed a lower technique failure rate of 0.08 [0.05–0.15] episodes per patient-year in APD-RPM versus 0.18 [0.12–0.26] in APD-without RPM cohort; incidence rate ratio = 0.45 95% confidence interval: [0.22–0.91], p-value = 0.03. Conclusions: The use of an RPM program in APD patients may be associated with a lower technique failure rate. More extensive and interventional studies are needed to confirm its potential benefits and to measure other patient-centered outcomes.
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