Conventional Peritoneal Dialysis Research Articles

Supplementation with high-dose trans-resveratrol improves ultrafiltration in peritoneal dialysis patients: a prospective, randomized, double-blind study

Background Ultrafiltration (UF) failure mostly contributes to technical failure in peritoneal dialysis (PD) patients, and one of its responsible factors is peritoneal angiogenesis. Resveratrol has been proposed to have an angiogenesis-ameliorating effect on tumor patients. We hypothesize trans-resveratrol has beneficial effects on angiogenesis-related markers in PD patients. Methods In this prospective, randomized, and double-blind trial, 72 patients were randomly assigned to 12-week treatment of low-dose or high-dose (150 or 450 mg/d) trans-resveratrol or a placebo. Visits were scheduled at 0, 4, 8, and 12 weeks after treatment. Clinical indices including 24-hour UF volume, UF rate, 24-hour urine volume, residual renal function, and dialysis adequacy (kt/v) were measured. Angiogenesis markers including vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), angiopoietin-2 (Ang-2), tyrosine kinase 2 (Tie-2), and thrombospondin-1 (Tsp-1) in peritoneal effluent were also assessed by enzyme-linked immunosorbent assay. Results Finally, 64 out of 72 patients were analyzed, 18 in the high-dose group, 22 in the low-dose group, and 24 in the placebo group. Over the 12-week period, patients in the high-dose group [mean change from baseline (95% CI): 171.4 (141.3-201.5) (mL), p = 0.003 (Net UF); 11.3(10.5-12.1) (mL/h), p = 0.02 (UF rate)] or the low-dose group [mean change from baseline (95% CI: 98.1 (49.5-146.7) (mL), p = 0.007 (Net UF); 6.5 (4.4-8.6) (mL/h), p = 0.04 (UF rate)] versus the placebo group had a significantly greater improvement in mean net UF volume and UF rate. The appearance rates of VEGF, Flk-1, and Ang-2 were more significantly reduced (appearance rates of Tie-2 and Tsp-1 increased) in the high-dose group versus the placebo group, but not in the low-dose group. Conclusion Supplementation with trans-resveratrol is beneficial to improve ultrafiltration in PD patients, and high-dose supplementation may improve ultrafiltration by ameliorating angiogenesis induced by conventional lactate-buffered PD solutions.

A modified peritoneal dialysis catheter with a new technique: Farewell to catheter migration.

To evaluate the efficacy our new, three-cuff peritoneal dialysis (PD) catheter, with the low-entry technique and to study its impact on catheter survival and mechanical and infectious complications, we prospectively used it in 36 incident PD patients and compared the results with those of conventional double-cuff PD Tenckhoff catheters with the classic approach used in 37 patients. The study was carried out at our university hospital over a period of 18 months. At the end of the study, significantly higher survival rate was observed with the use of new catheter compared with the conventional two-cuff Tenckhoff catheter, 91.7% and 73%, respectively, (P <0.01); the difference in catheter survival was due to a lower incidence (P < 0.01) of catheter-tip migration and a lower incidence (P <0.01) of peritonitis. Dialysis fill and drain times were significantly shorter and Kt/V was better with our new catheter. In conclusion, the study suggests superiority of our new catheter and our new technique over the conventional one in terms of catheter survival. This is due to less incidences of catheter tip migration in addition to lower peritonitis rates. Dialysis adequacy was better because of shortened fill and drain time.

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we examined the benefits of interleukin (IL)-10, which exerts anti-inflammatory effects, in an experimental rat model of methylglyoxal (MGO)-induced PF. We injected an adeno-associated virus (AAV) vector encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male Sprague-Dawley rats at 6 weeks of age. Four weeks later, the rats received continuous peritoneal injections of conventional PD fluid (PDF) with MGO for 3 weeks. Then, the peritoneal histology and the expression levels of fibrogenic mediators and proinflammatory cytokines were analyzed. The rats demonstrating persistent IL-10 expression showed significantly reduced fibrous peritoneal thickening compared with those with GFP expression. The infiltration of macrophages, the expression of tumor necrosis factor-α, IL-1β, IL-6, transforming growth factor-β1, Snail, and matrix metalloproteinase 2 genes as well as the proliferation of mesenchymal-like mesothelial cells augmented by MGO were all significantly suppressed by IL-10 expression. IL-10 also abrogated the extent of MGO-induced bowel adhesions mimicking a cocoon-like mass. Our findings provide valuable insight into the potential benefit of immunomodulation with IL-10 as one potentially effective therapeutic strategy for preventing the onset of peritoneal injury resulting in PF.

Update on Peritoneal Dialysis: Core Curriculum 2016

Update on Peritoneal Dialysis: Core Curriculum 2016

Effect of Neutral-pH, Low-Glucose Degradation Product Peritoneal Dialysis Solutions on Residual Renal Function, Urine Volume, and Ultrafiltration: A Systematic Review and Meta-Analysis.

Neutral-pH, low-glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A systematic review was performed evaluating the effect of these solutions on residual renal function, urine volume, peritoneal ultrafiltration, and peritoneal small-solute transport (dialysate to plasma creatinine ratio) over time. Multiple electronic databases were searched from January of 1995 to January of 2013. Randomized trials reporting on any of four prespecified outcomes were selected by consensus among multiple reviewers. Eleven trials of 643 patients were included. Trials were generally of poor quality. The meta-analysis was performed using a random effects model. The use of neutral-pH, low-glucose degradation products solutions resulted in better preserved residual renal function at various study durations, including >1 year (combined analysis: 11 studies; 643 patients; standardized mean difference =0.17 ml/min; 95% confidence interval, 0.01 to 0.32), and greater urine volumes (eight studies; 598 patients; mean difference =128 ml/d; 95% confidence interval, 58 to 198). There was no significant difference in peritoneal ultrafiltration (seven studies; 571 patients; mean difference =-110; 95% confidence interval, -312 to 91) or dialysate to plasma creatinine ratio (six studies; 432 patients; mean difference =0.03; 95% confidence interval, 0.00 to 0.06). The use of neutral-pH, low-glucose degradation products solutions results in better preservation of residual renal function and greater urine volumes. The effect on residual renal function occurred early and persisted beyond 12 months. Additional studies are required to evaluate the use of neutral-pH, low-glucose degradation products solutions on hard clinical outcomes.

Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The BAL Anz Trial

The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary biomarkers as tools to predict RRF decline in PD patients.

Increased peritoneal permeability at peritoneal dialysis initiation is a potential cardiovascular risk in patients using biocompatible peritoneal dialysis solution.

BackgroundCardiovascular disease is a frequent cause of death in peritoneal dialysis patients. Biocompatible peritoneal dialysis solutions with neutral pH have been anticipated to reduce cardiovascular disease more than conventional peritoneal dialysis solutions with low pH, but it remains unclear which factors at peritoneal dialysis initiation increase cardiovascular risk in patients using biocompatible peritoneal dialysis solutions. This study was undertaken to investigate which clinical factors at peritoneal dialysis initiation, including peritoneal transport status, are associated with cardiovascular event in patients using biocompatible peritoneal dialysis solution.MethodsThis retrospective cohort study of peritoneal dialysis patients using biocompatible solutions with neutral pH assessed relations of clinical parameters at peritoneal dialysis initiation to cardiovascular event during the subsequent five years.ResultsOf 102 patients who started peritoneal dialysis, cardiovascular event occurred in 18. Age, history of cardiovascular disease before peritoneal dialysis initiation, hemoglobin, serum albumin, C-reactive protein, peritoneal permeability defined by the ratio of dialysate to plasma creatinine concentration at 4 hr (D/Pcre) in peritoneal equilibration test (PET), number of patients in each PET category defined by D/Pcre, and peritoneal protein clearance significantly differed between patients with and without cardiovascular event. For patients divided according to PET category using Kaplan–Meier method, the group of high average to high peritoneal transporters exhibited significantly high incidence of cardiovascular event and mortality compared with the groups of low and low-average peritoneal transporters (Log rank; p = 0.0003 and 0.005, respectively). A Cox proportional hazards model showed independent association of PET category classification with cardiovascular event.ConclusionsPeritoneal permeability expressed as PET category at peritoneal dialysis initiation is an independent cardiovascular risk factor in peritoneal dialysis patients using biocompatible peritoneal dialysis solution with neutral pH. Greater peritoneal permeability at peritoneal dialysis initiation might reflect subclinical vascular disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2369-15-173) contains supplementary material, which is available to authorized users.

Peritoneal Fibrosis Induced by Intraperitoneal Methylglyoxal Injection: The Role of Concurrent Renal Dysfunction

Background: Peritoneal fibrosis (PF) is a serious pathophysiology of peritoneal dialysis (PD). An ongoing focus of research is the potential fibrogenic nature of methylglyoxal (MGO) in conventional PD fluid (PDF). The aim of the current study was to explore the effects of the uremic milieu on the promotion of PF by MGO using rats with adenine-induced renal failure (RF). Methods: Adenine-treated Sprague-Dawley rats were randomly assigned to receive continuous peritoneal injections of PDF with or without MGO for three weeks or were left untreated for the same duration. Rats without RF were also assigned to three groups. The peritoneal histology and expression levels of type I collagen, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (αSMA), Snail, matrix metalloproteinase-2 (MMP-2), advanced glycation end-products (AGEs) and the receptor for AGE (RAGE) were then analyzed. Results: Peritoneal treatment with 5 m<smlcap>M</smlcap> MGO accelerated the fibrous peritoneal thickening progression promoted by exposure to standard PDF in the rats with RF, but not in the rats with a normal renal function. Treatment with MGO significantly augmented the proliferation of mesenchymal-like mesothelial cells, accumulation of AGE, de novo expression of αSMA and RAGE and gene expression of type I collagen, TGF-β1, Snail and MMP-2, whereas both MGO and RF alone had, at most, marginal effects on the changes in these biological parameters. Conclusions: In the present study, the adverse effects of MGO on the peritoneum became more prominent under conditions of a uremic milieu. These findings imply that MGO and uremia act cooperatively to induce PF.

Structure- and concentration-specific assessment of the physiological reactivity of α-dicarbonyl glucose degradation products in peritoneal dialysis fluids.

In peritoneal dialysis (PD), glucose degradation products (GDPs), which are formed during heat sterilization of dialysis fluids, lead to structural and functional changes in the peritoneal membrane, which eventually result in the loss of its ultrafiltration capacity. To determine the molecular mechanisms behind these processes, the present study tested the influence of the six major α-dicarbonyl GDPs in PD fluids, namely, glyoxal, methylglyoxal, 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), and glucosone with respect to their potential to impair the enzymatic activity of RNase A as well as their effects on cell viability. For comprehensive risk assessment, the α-dicarbonyl GDPs were applied separately and in concentrations as present in conventional PD fluids. Thus, it was shown that after 5 days, glucosone impaired RNase A activity most distinctly (58% remaining activity, p < 0.001 compared to that of the control), followed by 3,4-DGE (62%, p < 0.001), 3-DGal (66%, p < 0.001), and 3-DG (76%, p < 0.01). Methylglyoxal and glyoxal caused weaker inactivation with significant effects only after 10 days of incubation (79%, 81%, p < 0.001). Profiling of the advanced glycation end products formed during the incubation of RNase A with methylglyoxal revealed predominant formation of the arginine modifications imidazolinone, CEA/dihydroxyimidazoline, and tetrahydropyrimidine at Arg10, Arg33, Arg39, and Arg85. Particularly, modification at Arg39 may severely affect the active site of the enzyme. Additionally, structure- and concentration-specific assessment of the cytotoxicity of the α-dicarbonyl GDPs was performed. Although present at very low concentration, the cytotoxic effect of PD fluids after 2 days of incubation was exclusively caused by 3,4-DGE (14% cell viability, p < 0.001). After 4 days of incubation, 3-DGal (13% cell viability, p < 0.001), 3-DG (24%, p < 0.001), and, to a lower extent, glyoxal and methylglyoxal (both 57%, p < 0.01) also reduced cell viability significantly. In conclusion, 3,4-DGE, 3-DGal, and glucosone appear to be the most relevant parameters for the biocompatibility of PD fluids.

Biocompatible dialysis fluids for peritoneal dialysis

The longevity of peritoneal dialysis (PD) is limited by high rates of technique failure, some of which stem from peritoneal membrane injury. 'Biocompatible' PD solutions have been developed to reduce damage to the peritoneal membrane. This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD. We searched the Cochrane Renal Group's Specialised Register (28 February 2013), through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE, and handsearching conference proceedings. All randomised controlled trials (RCTs) and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low glucose degradation product (GDP); neutral pH, bicarbonate (± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based PD solutions were excluded. Two authors extracted data on study quality and outcomes (including adverse effects). The authors contacted investigators to obtain missing information. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for categorical variables, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous variables. Thirty-six eligible studies (2719 patients) were identified: Neutral pH, lactate-buffered/bicarbonate (± lactate)-buffered, low GDP PD solution (24); icodextrin (12). Allocation methods and concealment were generally incompletely reported, and adequate in only ten studies (27.8%). Patients lost to follow-up ranged from 0% to 83.4%. Neutral pH, low GDP versus conventional glucose PD solutionBased on generally sub-optimal quality evidence, the use of neutral pH, low GDP PD solutions was associated with larger urine volumes at the end of the studies, up to three years of therapy duration (7 studies, 520 patients: MD 126.39 mL/d, 95% CI 26.73 to 226.05). Improved preservation of residual renal function was evident in studies with greater than 12 month follow-up (6 studies, 360 patients: SMD 0.31, 95% CI 0.10 to 0.52). There was no significant effect on peritonitis, technique failure or adverse events with the use of neutral pH, low GDP PD solutions. Glucose polymer (icodextrin) versus conventional glucose PD solutionThere was a significant reduction in episodes of uncontrolled fluid overload (2 studies, 100 patients: RR 0.30, 95% CI 0.15 to 0.59) and improvement in peritoneal ultrafiltration (4 studies, 102 patients, MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising residual renal function (4 studies, 114 patients: SMD 0.12, 95% CI -0.26 to 0.49) or urine output (3 studies, 69 patients: MD -88.88 mL/d, 95% CI -356.88 to 179.12) with icodextrin use. A comparable incidence of adverse events with the icodextrin (four studies) was reported. Based on generally sub-optimal quality studies, use of neutral pH, low GDP PD solution led to greater urine output and higher residual renal function after use exceeded 12 months. Icodextrin prescription improved peritoneal ultrafiltration and mitigated uncontrolled fluid overload. There were no significant effects on peritonitis, technique survival, patient survival or harms identified with their use. Based on the best available evidence, the use of these 'biocompatible' PD solutions resulted in clinically relevant benefits without added risks of harm.

The size-dependent efficacy and biocompatibility of hyperbranched polyglycerol in peritoneal dialysis

Glucose is a common osmotic agent for peritoneal dialysis (PD), but has many adverse side effects for patients with end-stage renal disease. Recently, hyperbranched polyglycerol (HPG) has been tested as an alternative osmotic agent for PD. This study was designed to further examine the efficacy and biocompatibility of HPG over a range of different molecular weights. HPGs of varying molecular weights (0.5 kDa, 1 kDa, 3 kDa) were evaluated in a preclinical rodent model of PD. HPG PD solutions were standardized for osmolality and compared directly to conventional glucose-based Physioneal™ PD solution (PYS). The efficacy of HPG solutions was measured by their ultrafiltration (UF) capacity, solute removal, and free water transport; biocompatibility was determined in vivo by the histological analysis of the peritoneal membrane and the cell count of detached peritoneal mesothelial cells (PMCs) and neutrophils, and in vitro cytotoxicity to cultured human PMCs. All the different sized HPGs induced higher UF and sodium removal over a sustained period of time (up to 8 h) compared to PYS. Urea removal was significantly higher for 1–3 kDa than PYS, and was similar for 0.5 kDa. Our analyses indicated that the peritoneal membrane exhibited more tolerance to the HPG solutions compared to PYS, evidenced by less submesothelial injury and neutrophil infiltration in vivo, and less cell death in cultured human peritoneal mesothelial cells. Free water transport analysis of HPG indicated that these molecules function as colloids and induce osmosis mainly through capillary small pores. We attribute the differences in the biocompatibility and osmotic activity of different sized HPGs to the differences in the polymer bound water measured by differential scanning calorimetry. These preclinical data indicate that compared to PYS, low MW HPGs (0.5–3 kDa) produces superior fluid and waste removal with better biocompatibility profile, suggesting that they are promising osmotic agents for PD.

Longitudinal Analysis of Peritoneal Fluid Transport and Its Determinants in a Cohort of Incident Peritoneal Dialysis Patients

There is a paucity of large longitudinal studies on the time course of peritoneal fluid transport. The aim of the present study was to longitudinally analyze changes in fluid transport and relevant solute transport parameters in patients treated with a conventional peritoneal dialysis (PD) fluid and, to mimic clinical reality, not selected for the presence or absence of ultrafiltration (UF) failure. This prospective single-center cohort study followed 138 consecutive incident PD patients from July 1994 until censoring in August 2004. The design was longitudinal, with repeated measures over time in each patient. Patients had undergone at least 1 and a maximum of 5 annual standard peritoneal permeability analyses (SPAs) using 3.86% glucose dialysate. A linear mixed model was used to analyze the longitudinal data. No differences in patient characteristics were present at baseline in relation to the number of available SPAs. There were also no differences in patient withdrawal during the years of follow-up. A gradual decline in fluid transport, expressed as free water transport (FWT), small-pore fluid transport (SPFT), and transcapillary UF (TCUF), was observed with duration of PD. The decline was mainly attributable to patients who developed UF failure. The time courses for the determinants of fluid transport, such as the reflection coefficient (σ) and the UF coefficient (LpA), were not different. However, they were associated with an increase in the mass transfer area coefficient of creatinine, reflecting the peritoneal vascular surface area. Fluid profiles for FWT and SPFT during a dwell can be explained by current knowledge of the three-pore model. Fluid transport declines with the duration of PD because of an increase in the vascular surface area, leading to a rapid dissipation of glucose as the osmotic agent. The absence of a trend in the time course of osmotic conductance and its constituents-that is, LpA and σ-suggests that, in an unselected population, these parameters are affected only late in the time course of PD.

Reverse autoperitoneal dialysis resulting in pseudo acute renal failure.

A rise in serum creatinine without acute kidney injury (AKI) is possible. In the last 5 years, three patients presented to us for high serum creatinine levels after binge drinking. We already reported on two of these three patients [1, 2]. For the first one, dialysis was instituted as the initial diagnosis was AKI. With the experience gained, the next two patients were examined specifically for a particular cause. They were not dialyzed. The data of the third patient were as follows: a 44-year-old male, admitted after a fall following binge alcohol consumption. He complained of painful abdominal distension and was anuric. Serum creatinine was 6.5 mg/dL (575 µmol/L), blood urea: 66 mg/dL (23.5 mmol/L), serum sodium 134 mmol/L and serum potassium 4.3 mmol/L. An abdominal ultrasound examination showed two normal kidneys, a normal urinary tract and presence of peritoneal fluid. In view of these findings, a bladder rupture was suspected and confirmed by cystoscopy. With bladder drainage, serum creatinine diminished to 3.5 and then 1.4 mg/dL (309–123.7 µmol/L). Laparotomy was done and a 4-cm tear on the dome of urinary bladder was surgically repaired. All three patients had similar histories: (i) an alcoholic binge, (ii) a trauma, (iii) sudden onset of abdominal pain and progressive distension (iv) anuria (v) elevated serum creatinine (vi) cystography revealing a tear in the bladder and (vii) improvement in serum creatinine on continuous bladder drainage. The data of these patients are given in supplementary Table S1. In the majority of bladder ruptures, there is a history of significant abdominal trauma. Following heavy alcohol intake, the distended bladder is very susceptible to injury and can be ruptured by a minor trauma. Alcohol-induced polyuria and impaired sensorium that removes cues for voiding cause overdistension of the bladder and rupture. The intoxicated patient may fail to recall the trauma. In a review of 20 isolated intraperitoneal bladder ruptures, the mean time between presentation and diagnosis was 5.4 days [3]. The diagnosis was based on a compatible history: suprapubic pain, anuria, hematuria and rapidly increasing ascites. The diagnosis was strengthened by rapidly rising serum creatinine without features of hypercatabolism. Continuous bladder drainage normalized laboratory abnormalities. Urinary bladder injuries after blunt or penetrating trauma are rare, owing to the bladder's anatomical position [4]. Bladder ruptures can be extraperitoneal, intraperitoneal or both, depending on the site of the injury. Intraperitoneal bladder ruptures are usually associated with blunt abdominal trauma (excluding iatrogenic causes), and unlike extraperitoneal leaks, they are not usually associated with pelvic fractures. Intraperitoneal ruptures usually occur at the dome of the bladder in contrast to extraperitoneal leaks which are most often lateral [4]. Non-traumatic rupture is even rarer and causes may be essentially divided as increase in intravesical pressure or weakening of the bladder wall. In most cases, spontaneous rupture occurs in the presence of a urothelial neoplasm or after pelvic radiation therapy [2]. In neonates, peritoneal entry of urine is a rare complication. The major causes are congenital obstructive uropathy with urine leakage into the peritoneal cavity and bladder perforation as a complication of umbilical artery catheterization [5]. The expression ‘reverse peritoneal dialysis’ was first used in 1991 [5]. It is characterized by a flux of small molecules such as creatinine and urea from urine collected in the peritoneum along a concentration gradient opposite to conventional peritoneal dialysis where small molecules move from the blood to peritoneal cavity, a phenomenon mentioned as ‘reverse autoperitoneal dialysis’. As a result, the blood values of creatinine and urea are elevated mimicking renal failure despite normally functioning kidneys. This was described as ‘pseudo acute renal failure’ in the literature.

"Ico-Alone" single nocturnal exchange to initiate peritoneal dialysis in patients with residual renal function-Five year, single centre experience

We analyzed the outcome of incremental dialysis with single nocturnal icodextrin exchange peritoneal dialysis (PD) as the initial treatment for end-stage kidney failure in patients who have significant residual renal function. All adult patients opting for PD as renal replacement therapy, having residual renal function, and urinary KT/V of 1.0 were offered incremental dialysis with single nocturnal icodextrin exchange as initial treatment. Adequacy of dialysis was calculated at 1, 3, and 6 months and then 6 monthly. Patients were shifted to conventional PD if short of adequacy or if clinically indicated. Median period on “Ico-alone,” peritonitis, exit site infection rates, and patient survival, while on this protocol, were calculated. These outcomes were compared with the cohort of contemporary patients on conventional PD. Thirteen patients were initiated on “Ico-alone” dialysis between October 2006 and October 2011. The baseline characteristics were similar when compared with cohort of conventional PD patients, except urine volume, which was more in “Ico-alone” group (1265 ± 316 vs. 551 ± 504, P = 0.000). Total KT/V at 3 months (1.63 ± 0.6 vs. 1.7 ± 0.2, P = 0.6) and at 1 year (1.64 ± 0.5 vs. 1.53 ± 0.3, P = 0.6) was similar to the cohort of conventional PD patients. Median period on “Ico-alone” was 9.6 months. Peritonitis rate was 1 episode in 56.22 vs 25.29 patient-months and exit site infection was 1 episode in 56.2 vs 189.71 patient-months in “Ico-alone” and conventional group, respectively. Patient survival was 42.84 months in “Ico-alone” vs 25.29 months in conventional dialysis (P = 0.01). In conclusion, single icodextrin exchange offers adequate dialysis in patients with residual renal function (KT/V = 1) for a median period of 9 months.

Effect of the Dialysis Fluid Buffer on Peritoneal Membrane Function in Children

Double-chamber peritoneal dialysis fluids exert less toxicity by their neutral pH and reduced glucose degradation product content. The role of the buffer compound (lactate and bicarbonate) has not been defined in humans. A multicenter randomized controlled trial in 37 children on automated peritoneal dialysis was performed. After a 2-month run-in period with conventional peritoneal dialysis fluids, patients were randomized to neutral-pH, low-glucose degradation product peritoneal dialysis fluids with 35 mM lactate or 34 mM bicarbonate content. Clinical and biochemical monitoring was performed monthly, and peritoneal equilibration tests and 24-hour clearance studies were performed at 0, 3, 6, and 10 months. No statistically significant difference in capillary blood pH, serum bicarbonate, or oral buffer supplementation emerged during the study. At baseline, peritoneal solute equilibration and clearance rates were similar. During the study, 4-hour dialysis to plasma ratio of creatinine tended to increase, and 24-hour dialytic creatinine and phosphate clearance increased with lactate peritoneal dialysis fluid but not with bicarbonate peritoneal dialysis fluid. Daily net ultrafiltration, which was similar at baseline (lactate fluid=5.4±2.6 ml/g glucose exposure, bicarbonate fluid=4.9±1.9 ml/g glucose exposure), decreased to 4.6±1.0 ml/g glucose exposure in the lactate peritoneal dialysis fluid group, whereas it increased to 5.1±1.7 ml/g glucose exposure in the bicarbonate content peritoneal dialysis fluid group (P=0.006 for interaction). When using biocompatible peritoneal dialysis fluids, equally good acidosis control is achieved with lactate and bicarbonate buffers. Improved long-term preservation of peritoneal membrane function may, however, be achieved with bicarbonate-based peritoneal dialysis fluids.

Biocompatible Peritoneal Dialysis Solution Preserves Residual Renal Function

Background/Aims: The long-term effects of biocompatible peritoneal dialysis (PD) solution on residual renal function (RRF), inflammation, adipokines and metabolic acidosis are controversial. We evaluated the effects of biocompatible PD solution in continuous ambulatory PD (CAPD) patients for an additional 12-month period. Method: Among 91 incident patients who started CAPD with either biocompatible PD solution (Balance®, Fresenius; LS, n = 48) or conventional PD solution (CAPD/DPCA®, Fresenius; CS, n = 43), 63 patients, who were followed for 12 months, were enrolled and followed for an additional 12 months. Results: After 24 months of treatment, the glomerular filtration rate (GFR) of the LS group was twofold higher compared to the CS group (33.5 ± 30.7 vs. 16.3 ± 17.9 l/week/1.73 m², respectively, p = 0.021). In a subgroup of patients with an initial GFR >2 ml/min/1.73 m², the GFR of the LS group was significantly higher than the rate of the CS group after 24 months (43.7 ± 30.5 vs. 18.6 ± 19.0 l/week/1.73 m², respectively, p = 0.042). Over a 24-month period, effluent cancer antigen-125 levels were significantly increased in the LS group compared to the CS group, while effluent interleukin-6 levels did not differ between the two groups. The serum tCO₂ levels were consistently higher in the LS group compared to the CS group. Conclusions: We found that the effect of LS on preserving RRF may be maintained over a 24-month treatment period in CAPD patients, and LS use may have other benefits, such as the correction of metabolic acidosis.

The Effects of Biocompatible Compared with Standard Peritoneal Dialysis Solutions on Peritonitis Microbiology, Treatment, and Outcomes: The Balanz Trial

A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products ("biocompatible") compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-related deaths were comparable in the two groups. Biocompatible PD fluid use was associated with a broad reduction in gram-positive, gram-negative, and culture-negative peritonitis that reached statistical significance for non-pseudomonal gram-negative organisms. Peritonitis hospitalization duration was shorter, and peritonitis severity was more commonly rated as mild in patients receiving biocompatible PD fluids, although other peritonitis outcomes were comparable between the groups.

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial

BackgroundThe balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function.MethodsAdult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months.ResultsOf the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference −0.004 per month, 95% confidence interval (95% CI) −0.005 to −0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9–39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups.ConclusionsBiocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted.

A Combination of Biocompatible Peritoneal Dialysis Solutions and Residual Renal Function, Peritoneal Transport, and Inflammation Markers: A Randomized Clinical Trial

The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. Prospective, randomized, controlled, open-label study. Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. RRF, daily urine volume, serum and dialysate cytokine levels. RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. Unblinded, relatively short follow-up; no formal sample-size calculations. Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.

Can Intensive Hemodialysis Prevent Loss of Functionality in the Elderly ESRD Patient?

Initiation of dialysis may be accompanied by decline in physical and cognitive function and independence, especially in the elderly ESRD patient. Here, we postulate the underlying factors, which may contribute to this observation in the elderly dialysis population, such as increased risk of dialysis-induced hypotension and associated cerebral and cardiac events, as well as malnutrition, infections, sleep abnormalities, and psychological complications of dialysis initiation. We describe an elderly dialysis patient who did well on nocturnal home hemodialysis (HD), and we hypothesize how intensive HD (i.e., nocturnal HD and/or short daily HD) may reduce the incidence of these dialysis complications and may therefore be considered as an option to attempt to preserve functional status and quality of life, especially early after the transition from predialysis to dialysis. Before general adoption of this strategy, further studies on the etiology of functional loss at the time of dialysis initiation, as well as on the potential advantageous effects of intensive HD in the elderly ESRD patient as compared with conventional HD, peritoneal dialysis and kidney transplantation, are required.