MO687FREE WATER TRANSPORT AND ABSOLUTE DIP OF DIALYSATE SODIUM CONCENTRATION: EARLY CLINICAL PARAMETERS FOR PERITONEAL FIBROSIS IN PD PATIENTS?

Background and Aims Reduction of peritoneal salt and water removal is an important cause of shortened patient and technique survival in peritoneal dialysis (PD). The aim of this study was to longitudinally analyze changes in fluid and solute transport parameters in PD patients during the first year of treatment, using peritoneal equilibration test (PET). Method Retrospective observational study of incident PD patients who underwent 4-hour 3.86% glucose PET with additional measurement of ultrafiltration at 1 hour, 1 month after PD initiation and 12 months later. Parameters of peritoneal transport such as dialysate-to-plasma ratio of creatinine (D/Pcreat), ultrafiltration at 1 and 4 hours, small-pore ultrafiltration (SPUF), free water transport (FWT), sodium removal and absolute dip of dialysate sodium concentration (ΔDNa) at 1 hour (as an expression of sodium sieving), were calculated. Serum cancer antigen 125 (CA-125) was also assessed. Clinical, analytical and demographic data were analyzed. Statistical analysis was performed using SPSS (Version 23 for Mac OSX). Results The average age of 16 incident PD patients was 58.69 ± 8.51 years, 10 (62.5%) were male and 5 (31.8%) were diabetic. Ten patients (62.5%) were on automated peritoneal dialysis (APD). One month after PD initiation, membrane characteristics were: D/P = 0.684 ± 0.589, total UF at 4h = 0.696 ± 0.283L, UF at 1h = 0.487 ± 0.162L, SPUF = 0.303 ± 0.359L, FWT = 0.207 ± 0.738L, %FWT = 51.855 ± 11.828%, sodium removal = 38.048 ± 16.087mmol/L and ΔDNa = 11.125 ± 3.34mmol/L. Average serum CA-125 was 51.206 ± 22.6U/mL. A paired sample t-test was performed to compare these parameters 1 and 12 months after PD initiation and revealed a statistically significant increase of 0.11± 0.196L (p=0.042) on SPUF and 18.607 ± 7.1mmol/L (p=0.019) on sodium removal. ΔDNa showed a decrease of 2.5 ± 0.743mmol/L (p=0.005) and % FWT of 11.782 ± 12.831% (p=0.002). FWT also showed a decrease of 0.168 ± 0.019L, total UF at 4h of 0.206 ± 0.142L and UF at 1h of 0.114 ± 0.243L, however did not reach statistical significance. D/Pcreat remained stable. CA-125 showed a mild decrease of 3.644 ± 22.364U/mL although not statistically significant. Pearson correlation revealed a positive correlation between the variation of total UF at 4h and the variation of FWT (r=0.553, p=0.026) and ΔDNa (r=0.503, p=0.047), but not with SPUF, sodium removal, D/Pcreat or CA-125, during the study follow-up period. Conclusion The reduction of FWT through aquaporins and, particularly, the reduction of ΔDNa as a sodium sieving measure, appear to be the first functional changes in peritoneal membrane, suggesting that fibrosis may begin soon after PD initiation. Our results indicate that FWT and ΔDNa can be used to access fibrotic peritoneal alterations earlier than other conventional parameters such as D/Pcreat.

P1131STEADY CONCENTRATION PERITONEAL DIALYSIS INCREASES ULTRAFILTRATION AND SODIUM REMOVAL COMPARED TO CAPD

Background and Aims Fluid and sodium removal may be a challenge during glucose-based PD, leading to increased use of high glucose solutions to maintain sufficient fluid removal. This may in turn lead to increased sodium sieving, resulting in a decreased sodium removal. Carry Life® UF uses Steady Concentration PD (SCPD), where the infusion of glucose compensates for glucose uptake and maintains the intraperitoneal glucose concentration at a sufficient level providing a continuous ultrafiltration throughout the dwell. The present study investigated the effect of Carry Life UF compared to a standard CAPD dwell regarding ultrafiltration, sodium removal and glucose absorption. Method Eight stable PD patients were included in the study. Subjects were treated with 5-hour Carry Life UF treatments using three different glucose doses (11, 14, 20 g/h). An initial fill with 1500 ml, 13.6 g/l glucose PD solution was used. A small volume of dialysate was drained hourly to avoid overfill. A standard 4-hour Peritoneal Equilibration Test (PET) (2000 ml, 22.7 g/l glucose) was used as control. Data expressed as mean ± SD, statistical analysis using one-way ANOVA. Results Ultrafiltration was significantly increased during the Carry Life UF treatments compared to PET (646±256, 739±312, 863±380 ml for 11 g/h, 14 g/h and 20 g/h, respectively, vs. 162±242 ml for PET, p<0.01). Sodium removal increased significantly during Carry Life UF treatments (86±27, 92±33, 110±37 mmol/dwell for 11, 14, and 20 g glucose/h) compared to PET (22±33 mmol/dwell, p<0.001). Figure a shows that the intraperitoneal glucose concentration increased during the first hours of the Carry Life UF treatments and remained stable during the remainder of the treatments. During PET the glucose concentration decreased gradually during the treatment. The maximum intraperitoneal glucose concentration did not exceed 26 g/l (144 mmol/l) during the Carry Life UF treatments. The UF volume per gram of glucose uptake was significantly higher for the two lower Carry Life UF glucose doses compared to PET (Figure b). Conclusion SCPD performed with Carry Life® UF maintained a stable intraperitoneal glucose concentration during the 5-hour treatment which generated significantly higher UF volumes compared to 4-hour PET. During the Carry Life UF treatments glucose was used more efficiently, particularly for the two lowest doses, in comparison to PET. The increased sodium removal with Carry Life® UF enables a better balance between UF volume and sodium removal than for example during APD. In summary, SCPD using Carry Life® UF increases the efficiency of PD compared to standard, glucose-based CAPD with respect to ultrafiltration and sodium removal.

P1149PERITONEAL MEMBRANE CHARACTERISTICS OVER TIME: A LONGITUDINAL STUDY

Background and Aims Modified PET (use of 3.86% glucose dialysate instead of 2.27%) and temporal drainage at one hour allows a more complete study of peritoneal membrane transport, as it provides information about sodium sieving, free water transport (FWT) and ultrafiltration failure (UFF). Longitudinal data using this PET are sporadic. Aims of our study were a) longitudinal follow-up of the membrane function using modified PET b) evaluation of UFF and association with clinical and membrane characteristics. Method We analyzed all modified PET tests performed in our unit during the last 9 years. Patients who underwent the first test during the first year of treatment and then once a year were included. We estimated classic peritoneal transport parameters like D/P creatinine, D/D0 glucose and ultrafiltration (UF) at 4 hours. Moreover we calculated sodium seiving expressed as Dip/DPNa= (Dialysate sodium time 0/plasma sodium)-(Dialysate sodium time 1 hour/plasma sodium)], sodium removal (in one hour) and FWT. We collected clinical and lab data of the patients too. Results A total of 219 PETs were performed in 85 PD patients, (median age 64 years (range 18-45). The baseline membrane characteristics of the patients were: DP creatinine=0.74±0.11, D/D0glucose=0.28±0.08, DipDPNa=0.05±0.04, sodium removal=29,804 ±26,894 (mmol/L), FWT=214.9±194.7 ml and UF =655.1±265.5 ml. On multivariate regression analysis D/P creatinine, FWT and sodium removal were significant independent covariates accounting for 50% of the variability of ultrafiltration . The patients were followed-up for a median of 36 months (range 2.4-143).For the repeated measurements, the analysis showed that the observed values of D/Pcre,D/D0, Dip/DPNa, FWT and UF remained rather stable across the different time measurements. During the study, 23 out of 85 pts developed peritoneal UF failure (UFF). Analysis was performed using univariate random effects logistic time-series models and only D/D0 (OR=0.84, P=0.001), D/P Cre (OR=1.15, p<0.001), urine volume (OR=1.26, p=0.027) and sodium removal (OR=0.99, p=0.003) were significantly associated with relative risk of UFF development. Conclusion Surprisingly, our patients present a stable membrane function over time. Possible explanations could be the low peritonitis rate and strict use of hypertonic glucose dialysates. Ultrafiltration failure was correlated with higher D/P creatinine and lower D/D0 glucose values, higher baseline urine volume and lower sodium sieving.

A Large Intraperitoneal Residual Volume Hampers Adequate Volumetric Assessment of Osmotic Conductance to Glucose

Background In end-stage renal disease patients treated with peritoneal dialysis (PD), the osmotic conductance to glucose (OCG) represents the intrinsic ability of the membrane to transport water in response to a crystalloid osmotic gradient. A progressive loss of OCG in long-term PD patients indicates the development of fibrosis in the peritoneal interstitium, and helps identify patients at risk for encapsulating peritoneal sclerosis. The double mini-peritoneal equilibration test (PET) has been proposed as a simple method to assess OCG using the difference in initial ultrafiltration rates generated by 2 successive dwells using 1.36% and 3.86% glucose-based, 1-h PET. However, the presence of a large peritoneal residual volume (RV) may potentially interfere with the correct evaluation of drained volumes, limiting the reliability of OCG assessed by the double mini-PET. Methods We retrospectively reviewed data from 53 peritoneal function tests in 35 consecutive PD patients starting PD at our center between March 2013 and March 2017. The test consisted of a uni-PET (double mini-PET combined with a 3.86%, 4-h PET) performed at PD start, then yearly. In addition to peritoneal solute transport rate and net ultrafiltration, the tests provided information about osmotic water transport (OCG, sodium sieving, and free-water transport) as well as the RV estimated from albumin dilution. Results Contrary to sodium sieving, net ultrafiltration, and free-water transport, OCG did not correlate with any of the other parameters of osmotic water transport. In multivariate regression analyses, the RV was identified as the only determinant of OCG, while it did not alter the robust association between sodium sieving/free-water transport and their respective determinants. Considering only baseline tests or the whole series of tests, the presence of a large intraperitoneal RV was associated with discrepant values between OCG and sodium sieving, and with an artificial increase in OCG. Conclusions A large RV leads to significant overestimation of OCG using the double mini-PET, potentially reducing the ability of OCG to identify patients with progressive fibrosis in the peritoneal interstitium. On the other hand, sieving of the dialysate sodium, a biochemical surrogate for OCG, is independent of the RV and may therefore be more reliable. A call for caution is warranted in patients with a large RV to avoid misinterpretation of OCG values derived from the double mini-PET.

Peritoneal Equilibration Test Reference Values Using A 3.86% Glucose Solution during the First Year of Peritoneal Dialysis: Results of a Multicenter Study of a Large Patient Population

BackgroundThe original peritoneal equilibration test (PET) was used to classify peritoneal dialysis (PD) patients using a 2.27% glucose solution. It has since been suggested that a 3.86% glucose solution be used because this provides better information about ultrafiltration (UF) capacity and the sodium (Na) sieving of the peritoneal membrane.ObjectiveThe aim of this study was to determine reference values for a PET using a 3.86% glucose solution (PET-3.86%).MethodsWe evaluated the PET-3.86% in a large population of incident PD patients attending 27 Italian dialysis centers.ResultsWe evaluated the results of 758 PET-3.86% in 758 incident PD patients (1 test per patient). The mean duration of PD was 5 ± 3 months. The ratio of the concentrations of creatinine in dialysate/plasma (D/PCreat) was 0.73 ± 0.1 (median 0.74). The ratio between the concentrations of glucose at the end/beginning of the test (D/D0) was 0.25 ± 0.08 (median 0.24). Ultrafiltration uncorrected and corrected for bag overfill was respectively 776 ± 295 mL (median 781 mL) and 675 ± 308 mL (median 689 mL). Sodium sieving was 8.4 ± 3.8 mmol/L (median 8.0 mmol/L).ConclusionThe results of the study provide PET-3.86% reference values for the beginning of PD that can be used to classify PD patients into transport classes and monitor them over time.

Ultrafiltration Failure and Impaired Sodium Sieving during Long-Term Peritoneal Dialysis: More than Aquaporin Dysfunction?

Fifteen years ago, our group reported the case of a 67-year-old man on peritoneal dialysis for 11 years, in whom ultrafiltration failure and impaired sodium sieving were associated with an apparently normal expression of aquaporin-1 (AQP1) water channels in peritoneal capillaries. At that time, AQP1 dysfunction was suggested as the cause of impaired free-water transport. However, recent data from computer simulations, and structural and functional analysis of the peritoneal membrane of patients with encapsulating peritoneal sclerosis, demonstrated that changes in the peritoneal interstitium directly alter osmotic water transport. In light of these insights, we challenge the initial hypothesis and provide several lines of evidence supporting the diagnosis of encapsulating peritoneal sclerosis in this patient and suggesting that severe peritoneal fibrosis accounted for the loss of osmotic conductance developed during the course of peritoneal dialysis.

Ultrafiltration Failure in Peritoneal Dialysis: A Pathophysiologic Approach

Background: Ultrafiltration failure is a significant cause of technique failure for peritoneal dialysis and subsequent transfer to hemodialysis. Summary: Ultrafiltration failure is defined as failure to achieve at least 400 ml of net ultrafiltration during a 4 h dwell using 4.25% dextrose. Four major causes of ultrafiltration failure have been described. A highly effective peritoneal surface area is characterized by transition to a very rapid transport state with D/P creatinine >0.81. Low osmotic conductance to glucose is characterized by attenuation of sodium sieving and decreased peritoneal free water clearance to <26% of total ultrafiltration in the first hour of a dwell. Low effective peritoneal surface area manifests with decreases in the transport of both solute and water. A high total peritoneal fluid loss rate is the most difficult to diagnose clinically; failure to achieve ultrafiltration with an 8-10 h icodextrin dwell may provide a clue to diagnosis. Key Messages: Knowledge of the specific pathophysiology of the various causes of ultrafiltration failure will aid in the diagnosis thereof.

Two-in-One Protocol: Simultaneous Small-Pore and Ultrasmall-Pore Peritoneal Transport Quantification

BackgroundReduced free water transport (FWT) through ultrasmall pores contributes to net ultrafiltration failure (UFF) and should be seen as a sign of more severe functional deterioration of the peritoneal membrane. The modified peritoneal equilibration test (PET), measuring the dip in dialysate Na concentration, estimates only FWT. Our aim was to simultaneously quantify small-solute transport, FWT, and small-pore ultrafiltration (SPUF) during a single PET procedure.MethodsWe performed a 4-hour, 3.86% glucose PET, with additional measurement of ultrafiltration (UF) at 60 minutes, in 70 peritoneal dialysis patients (mean age: 50 ± 16 years; 61% women; PD vintage: 26 ± 23 months). We calculated the dialysate-to-plasma ratios (D/P) of creatinine and Na at 0 and 60 minutes, and the Na dip (DipD/PNa60,), the delta dialysate Na 0–60 (ΔDNa0–60), FWT, and SPUF.ResultsSodium sieving (as measured by ΔDNa0–60) correlated strongly with the corrected DipD/PNa60, ( r = 0.85, p < 0.0001) and the corrected FWT ( r = 0.41, p = 0.005). Total UF showed better correlation with FWT than with indirect measurements of Na sieving ( r = 0.46, p < 0.0001 for FWT; r = 0.360, p < 0.0001 for DipD/PNa60,). Corrected FWT fraction was 0.45 ± 0.16. A negative correlation was found between time on PD and both total UF and FWT ( r = -0.253, p = 0.035 and r = -0.272, p = 0.023 respectively). The 11 patients (15.7%) diagnosed with UFF had lower FWT (89 mL vs 164 mL, p < 0.05) and higher D/P creatinine (0.75 vs 0.70, p < 0.05) than did the group with normal UF. The SPUF correlated positively with FWT in the normal UF group, but negatively in UFF patients ( r = -0.709, p = 0.015). Among UFF patients on PD for a longer period, 44.4% had a FWT percentage below 45%.ConclusionsMeasurement of FWT and SPUF is feasible by simultaneous quantification during a modified 3.86% glucose PET, and FWT is a decisive parameter for detecting causes of UFF in addition to increased effective capillary surface.

N-Acetylcysteine Improves Residual Renal Function in Peritoneal Dialysis Patients: A Pilot Study

BackgroundPreservation of peritoneal membrane function and residual renal function is important for the optimal care of peritoneal dialysis patients. N-Acetylcysteine may ameliorate oxidative stress, which is thought to be involved in peritoneal membrane dysfunction. In addition, N-acetylcysteine may have a positive effect on renal function in the setting of nephrotoxic contrast media administration. The aim of this study was to investigate the effect of N-acetylcysteine on peritoneal and residual renal function in peritoneal dialysis patients.MethodsTen prevalent peritoneal dialysis patients were administered oral N-acetylcysteine 1200 mg twice daily for 4 weeks. At baseline and at the end of treatment, peritoneal membrane function and residual renal function were assessed using a 4.25% dextrose peritoneal equilibration test and 24-hour dialysate and urine collection for calculation of peritoneal and residual renal Kt/V and mean urea and creatinine residual renal clearance.ResultsNo significant changes were demonstrated in peritoneal membrane function, including dialysate-to-plasma creatinine ratio, sodium sieving, and net ultrafiltration. Residual renal function improved significantly: urine volume increased from 633 ± 426 to 925 ± 552 mL/24 hours ( p = 0.022), residual renal Kt/V increased from 0.56 ± 0.41 to 0.75 ± 0.47 ( p = 0.037), and mean residual urea and creatinine clearance increased from 4.96 ± 3.96 to 5.95 ± 4.08 mL/min/1.73 m2( p = 0.059).ConclusionsN-acetylcysteine may improve residual renal function in patients treated with peritoneal dialysis.

Influence of the Preceding Dwell Time on the Peritoneal Equilibration Test with 3.86% Glucose Solution in Automated Peritoneal Dialysis

ObjectiveThe peritoneal equilibration test (PET) using 3.86% glucose solution is preceded by a long dwell with 3.86% glucose solution. A point of concern in patients treated with automated peritoneal dialysis (APD) is the influence of the preceding short nightly dwells on the results of a standardized PET. The aim of the study was to compare net ultrafiltration, small solute transport, sodium sieving, and solute transport type between a PET preceded by a long night dwell and one preceded by short (APD) dwells.Patients and Methods13 stable APD patients (mean age 60 ± 15 years; mean duration of peritoneal dialysis 31 ± 15 months) underwent 2 PETs: 1 preceded by short nightly dwells (PET A) and 1 preceded by a long night dwell (PET B).ResultsBoth PETs were performed within a mean period of 8 (range 5 – 11) days. Mean total ultrafiltration of PET A was 626 ± 218 mL and PET B was 644 ± 223 mL (NS). The 4-hour results of both tests for dialysate-to-plasma (D/P) ratios of creatinine and urea, Dt/D0ratios of glucose, and the dip in D/P sodium (sodium sieving) were similar. Classification of transport categories was identical for 10 of 13 patients.ConclusionIn APD, the preceding dwell time of a 3.86% glucose PET does not influence fluid transport, solute transport, or transport type.