Incremental peritoneal dialysis in incident end-stage kidney disease patients

Background: This retrospective cohort study investigated the characteristics and outcomes of the end-stage kidney disease (ESKD) patients treated with incremental peritoneal dialysis (PD) at a large academic centre. Methods: ESKD patients initiating PD with a dialysate volume ≤6 L/day were analysed. Results: One hundred and seventy-five patients were included and were followed up for 352.6 patient-years. The baseline residual kidney function (RKF) was 8.3 ± 3.4 mL/min/1.73 m2. The unadjusted 1- to 5-year patient survival rate was 89.6%, 80.4%, 65.4%, 62.7% and 48.8%, respectively, and the corresponding time on PD therapy rate was 95.1%, 89.1%, 89.1%, 82.4% and 77.6%. Greater initial PD dose (hazard ratio = 1.608, 95% confidence interval 1.089–2.375) was associated with death after adjusting for age, Charlson comorbidity index (CCI), haemodialysis prior to PD, assisted PD and baseline RKF, likely as a result of residual confounding. There was no association with PD discontinuation. The average peritonitis rate and hospitalisation rate were 0.122 and 0.645 episodes per patient-year, respectively. The dialysate volume increased from 4.5 (4.3–5.7) L/day to 8.0 (6.0–9.8) L/day at 5 years. Fifty-seven (32.6%) patients graduated to full-dose PD at a median time of 10.3 (6.2, 15.7) months. Male sex, greater body mass index and lower baseline serum albumin were risk factors for increasing PD dose to over 6 L/day within 1 year. Conclusions: Incremental PD is a safe approach to initiate dialysis, and it offers satisfactory outcomes. Close monitoring, comprehensive evaluation of clinical responses and prompt adjustment of the prescription as needed play a crucial role in this patient-centred treatment.

Peritoneal dialysis for acute kidney injury: Equations for dosing in pandemics, disasters, and beyond

Background: Peritoneal dialysis (PD) is a viable option for renal replacement therapy in acute kidney injury (AKI), especially in challenging times during disasters and pandemics when resources are limited. While PD techniques are well described, there is uncertainty about how to determine the amount of PD to be prescribed toward a target dose. The aim of this study is to derive practical equations to assist with the prescription of PD for AKI. Methods: Using established physiological principles behind PD clearance and membrane transport, a primary determinant of dose delivery, equations were mathematically derived to estimate dialysate volume required to achieve a target dose of PD. Results: The main derivative equation is VD = (1.2 × std- Kt/ V × TBW)/( t dwell + 4), where VD is the total dialysate volume per day, std- Kt/ V is the desired weekly dose, TBW is the total body water, and t dwell is the dwell time. VD can be expressed in terms of dwell volume, v dwell, by VD = (0.3 × std- Kt/ V × TBW) − (6 × v dwell). Two further equations were derived which directly describe the mathematical relationship between t dwell and v dwell. A calculator is included as an Online Supplementary Material. Conclusions: The equations are intended as a practical tool to estimate solute clearances and guide prescription of continuous PD. The estimated dialysate volume required for any dose target can be calculated from cycle duration or dwell volume. However, the exact target dose of PD is uncertain and should be adjusted according to the clinical circumstances and response to treatment. The equations presented in this article facilitate the adjustment of PD prescription toward the targeted solute clearance.

Intraperitoneal vancomycin for peritoneal dialysis-associated peritonitis in children: Evaluation of loading dose guidelines

Background: Current pediatric International Society for Peritoneal Dialysis guidelines for initial treatment of peritoneal dialysis (PD)-associated peritonitis suggest either monotherapy with cefepime or double therapy with first-generation cephalosporin or glycopeptide and ceftazidime or aminoglycoside. When using vancomycin, the intraperitoneal (IP) recommended pediatric loading dosage is 1000 mg/L of dialysate. This is based on adult pharmacokinetic (PK) studies and roughly translates to the adult recommendation where 30 mg/kg in 2 L is approximately 1000 mg/L. However, since the dialysate volume in pediatric patients is normalized to body surface area and not weight, the current recommended dosing can result in high vancomycin exposure in children. Vancomycin can potentially cause adverse effects. We aimed to determine if the IP vancomycin dosing of 1000 mg/L was causing elevated vancomycin levels and to offer possible dosing recommendations based on PK modeling and simulation. Methods: Retrospective review of pediatric patients who had been treated with IP vancomycin for PD-associated peritonitis. Vancomycin levels obtained for clinical monitoring were analyzed using NONMEM to generate population and individual (empiric Bayesian) estimates of vancomycin PK parameters and estimated peak levels. Predicted vancomycin peaks were also simulated from virtual pediatrics patients 3–70 kg following various dosing strategies. Results: Six episodes of peritonitis in three patients were analyzed. In the two episodes treated with 1000 mg/L, the first vancomycin levels (h post) were 95.6 ug/mL (3) and 49 (33) and following 500 mg/L were 33.2 (11), 30.2 (11), 23.6 (24), and 22.1 (11). All patients were cured of their peritonitis without the need for catheter removal. Based on our population PK model, a 1000 mg/L IP vancomycin loading dose will typically result in peak > 50 mg/L in patients weighing <35 kg and >60 mg/L in patients <15 kg. Vancomycin levels will remain above 20 mg/L for over 2 days without additional vancomycin dosing. Conclusion: The data suggest that a loading dose of vancomycin 1000 mg/L leads to higher than desired vancomycin levels and should be lowered. A 500 mg/L loading dosing appears more appropriate and needs further study.

P1055REMARKABLE REMOVALS OF BETA-2-MICROGLOBULIN AND PHOSPHATE WITH SHORT-DAILY HOME HEMODIALYSIS USING LOW DIALYSATE FLOW RATE

Background and Aims Short-daily hemodialysis (HD) with low-dialysate volume is an appealing portable dialysis approach for home use. Although this type of HD has proved being effective for the volume control and the clearance of low molecular-weight uremic toxins, limited data are available on the impact on the removal rates of other uremic toxins like β2-microglobulin (β2M) or phosphate (P), whose clearance is limited by sequestration into compartments, poor diffusion, high time-dependency, or protein binding. We evaluated the impact of short-daily HD with slow dialysate flow rate on the removal of solutes of different molecular weights and distribution volumes. Method Single-session and weekly balances of β2M, P, urea, and creatinine were prospectively assessed with total dialysate collection and serum measurements before and after 341 dialysis sessions (mean dialysate volume: 30963 ± 862 mL; mean length of dialysis session: 153 ± 8 min) in 31 stable patients (female; 9, 29 %; mean age: 55.6 ± 13.6 y; dry weight: 74.9 ± 13.3 kg) undergoing short-daily home HD with NxStage cycler, between July 2014 and October 2019. The mean blood flow rate was 365 ± 17 mL/min, whereas the mean dialysate flow rate was 194 ± 12 mL/min. Results Single-session β2M, P, urea, and creatinine removals were 0.138 ± 0.050 g, 0.610 ± 0.161 g, 18.89 ± 6.07 g and 1.07 ± 0.31 g, respectively, whereas the reduction rates (%) were 38.0 ± 13.0, 46.8 ± 8.6, 48.2 ± 7.0 and 46.6 ± 6.6, for β2M, P, urea and creatinine, respectively. The estimated weekly β2M, P, urea and creatinine removals in HDD patients dialyzing 5-6 days per week were comparable with 4-h in-center thrice-weekly on-line hemodiafiltration according to previous studies (Table 1). Conclusion Treating patients with short-daily HD with low-dialysate volume at a 5-6 days per week prescription may achieve an efficient weekly β2M and P removal.

Association of adipocytokines with peritoneal function

Background: Preservation of peritoneal function is crucial for the continuation of peritoneal dialysis (PD). A previous study suggested that blood cholesterol is involved in the preservation of peritoneal function; therefore, we determined whether adipocytokines can predict peritoneal function preservation. Methods: Eighty patients were enrolled. Serum adiponectin, leptin, apelin, various blood components, and estimated glomerular filtration rate (eGFR) (mL/min/m2) were measured. In addition, the duration of PD, presence or absence of peritonitis and diabetes mellitus, body mass index, urine output, peritoneal Kt/ V, renal Kt/ V, weekly Kt/ V, peritoneal creatinine clearance rate (CCr), renal CCr, weekly CCr, use or nonuse of statin products, dialysate volume, glucose exposure, and use or nonuse of icodextrin dialysate were assessed. Peritoneal equilibration tests were performed at 6-month intervals, and dialysate-to-plasma [D/P] ratio and glucose uptake ratio [D/D0] were measured. Associations of the baseline values and their percent changes with various adipocytokines and test items were evaluated. Results: Multiple regression analyses identified adiponectin ( p = 0.0392, p = 0.0348) as a significant predictive factor of D/P and D/D0 ratios. eGFR was identified as a significant predictive factor ( p = 0.015) of percent change in the D/P ratio. Apelin ( p = 0.0484), high-density lipoprotein cholesterol ( p = 0.0066), dialysate volume ( p = 0.0223), and urine output ( p = 0.0020) were identified as factors affecting the duration of PD. Conclusions: Adipocytokines are a predictive factor of peritoneal function and the duration of PD in patients undergoing PD.

Monitoring of Intraperitoneal Fluid Volume during Peritoneal Equilibration Testing using Segmental Bioimpedance

Background: Ultrafiltration failure and fluid overload are common in peritoneal dialysis (PD) patients. Knowledge of intraperitoneal volume (IPV) and time to peak IPV during a dwell would permit improved PD prescription. This study aimed to utilize trunk segmental bioimpedance analysis (SBIA) to quasi-continuously monitor IPV (IPVSBIA) during the peritoneal dwell. Methods: IPVSBIA was measured every minute using lower-trunk SBIA (Hydra 4200; Xitron Technologies Inc., CA, USA) in 10 PD patients during a standard 240-min peritoneal equilibration test (PET). The known dialysate volume (2 L) rendered IPVSBIA calibration and calculation of instantaneous ultrafiltration volume (UFVSBIA) possible. UFVSBIA was defined as IPVSBIA – 2 L. Results: Based on dialysate-to-plasma creatinine ratio, 2 patients were high, 7 high-average, and 1 low-average transporters. Technically sound IPVSBIA measurements were obtained in 9 patients (age 59.0 ± 8.8 years, 7 females, 5 African Americans). Drained ultrafiltration volume (UFVdrain) was 0.47 ± 0.21 L and correlated (r = 0.74; p < 0.05) with end-dwell UFVSBIA (0.55 ± 0.17 L). Peak UFVSBIA was 1.04 ± 0.32 L, it was reached 177 ± 61 min into the dwell and exceeded end-dwell UFVSBIA by 0.49 ± 0.28 L (95% CI: 0.27–0.7) and UFVdrain by 0.52 ± 0.31 L (95% CI: 0.29–0.76), respectively. Conclusion: This pilot study demonstrates the feasibility of trunk segmental bioimpedance to quasi-continuously monitor IPVSBIA and identify the time to peak UFVSBIA during a standard PET. Such new insights into the dynamics of intraperitoneal fluid volume during the dwell may advance our understanding of the underlying transport physiology and eventually assist in improving PD treatment prescriptions.

Removal of Different Classes of Uremic Toxins in APD vs CAPD: A Randomized Cross-Over Study

♦AimIn this study, we investigated, and this for the different classes of uremic toxins, whether increasing dialysate volume by shifting from continuous ambulatory peritoneal dialysis (CAPD) to higher volume automated peritoneal dialysis (APD) increases total solute clearance.♦MethodsPatients on peritoneal dialysis were randomized in a cross-over design to one 24-hour session of first a CAPD regimen (3*2 L of Physioneal 1.36% and 1*2 L of icodextrin) or APD (consisting of 5 cycles of 2 L Physioneal 1.36 and 1 cycle of 2 L Extraneal), and the other week the alternate regime, each patient serving as his/her own control. Dialysate, blood and urine samples were collected and frozen for later batch analysis of concentrations of urea, creatinine, phosphorus, uric acid, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, indoxyl sulfate, indole acetic acid, and p-cresyl sulfate. For the protein-bound solutes, total and free fractions were determined. Total, peritoneal and renal clearance (K) and mass removal (MR) of each solute were calculated, using validated models.♦ResultsIn 15 patients (11 male, 3 diabetics, 56 ± 16 years, 8 on CAPD, time on peritoneal dialysis 12 ± 14 months, and residual renal function of 9.9 ± 5.4 mL/min) dialysate over plasma ratio for creatinine (D/Pcrea) was 0.62 ± 0.10. Drained volume and obtained ultrafiltration were higher with APD vs CAPD (13.3 ± 0.5 L vs 8.5 ± 0.7 L and 1.3 ± 0.5 L vs 0.5 ± 0.7 L), whereas urine output was lower (1.0 ± 0.5 L vs 1.4 ± 0.6 L). Total clearance and MR tended to be higher for CAPD vs APD for all small and water soluble solutes, but mainly because of higher renal contribution, with no difference in the peritoneal contribution. For the protein-bound solutes, no differences in clearance or mass removal were observed.♦ConclusionAlthough the drained dialysate volume nearly doubled, APD did not result in better peritoneal clearance or solute removal vs classic CAPD. APD resulted in better ultrafiltration, but at the expense of residual urinary output and clearance.