The advantages of an incremental dialysis start are not fully clear. We aimed to evaluate the association of incremental initiation of peritoneal dialysis with mortality.
Incident peritoneal dialysis patients with a catheter placed at our hospital between 2008 and 2017 were included. All patients were followed up until December 31, 2019. Patients were categorized into different groups according to the initial daily dialysis exchanges, and were matched at a ratio of 1:2 with propensity score matching. Multiple variables including age, sex, residual kidney function, urine volume, hemoglobin, serum albumin and other important variables were included for the matching. Primary outcomes were all-cause and cardiovascular mortality.
A total of 1315 patients with a mean age of 45.9 years were enrolled. The mean glomerular filtration rate was 4.32 ml/min/1.73 m2 at start of dialysis. Two hundred eighty-five patients in the incremental group and 502 in the full dose group were matched for age, sex, residual kidney function, urine volume, hemoglobin, serum albumin and other important variables. Patient survival and cardiovascular event-free survival were similar between the two groups. However, during the first 6 years of peritoneal dialysis, patients in the incremental group had better survival (P = 0.011) and cardiovascular event-free survival (P = 0.044) than the full dose group, while such advantages disappeared when dialysis vintage became longer. Further analysis showed that the incremental group (vs full dose dialysis) had a 39% lower risk (95% CI 0.42-0.90, P = 0.012) of all-cause mortality and a 41% decreased risk (95% CI 0.35-0.99, P = 0.047) of cardiovascular mortality during the first 6 years of dialysis. Additionally, the cumulative hazard for anuria was significantly lower in the incremental group versus the full dose group (P = 0.006).
Our study shows a time-related survival advantage for incremental peritoneal dialysis patients, suggesting that an incremental regimen for starting peritoneal dialysis is feasible and is not associated with worse outcomes. Graphical Abstract presenting schematically the measurements of the solvation response function by processing the relevant streak camera images and the time-correlated photon counting (TCSPC) data and appropriately combining them together.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Incremental peritoneal dialysis (PD), defined as less than Full-dose PD prescription, has several possible merits, including better preservation of residual kidney function (RKF), lower peritoneal glucose exposure and reduced risk of peritonitis. The aims of this study were to analyse the association of Incremental and Full-dose PD strategy with RKF and urine volume (UV) decline in patients commencing PD.
Incident PD patients who participated in the balANZ randomised controlled trial (RCT) (2004-2010) and had at least one post-baseline RKF and UV measurement was included in this study. Patients receiving <56 L/week and ≥56 L/week of PD fluid at PD commencement were classified as Incremental and Full-dose PD, respectively. An alternative cut-point of 42 L/week was used in a sensitivity analysis. The primary and secondary outcomes were changes in measured RKF and daily UV, respectively.
The study included 154 patients (mean age 57.9 ± 14.1 years, 44% female, 34% diabetic, mean follow-up 19.5 ± 6.6 months). Incremental and Full-dose PD was commenced by 45 (29.2%) and 109 (70.8%) participants, respectively. RKF declined in the Incremental group from 7.9 ± 3.2 mL/min/1.73 m2 at baseline to 3.2 ± 2.9 mL/min/1.73 m2 at 24 months (p < 0.001), and in the Full-dose PD group from 7.3 ± 2.7 mL/min/1.73 m2 at baseline to 3.4 ± 2.8 mL/min/1.73 m2 at 24 months (p < 0.001). There was no difference in the slope of RKF decline between Incremental and Full-dose PD (p = 0.78). UV declined from 1.81 ± 0.73 L/day at baseline to 0.64 ± 0.63 L/day at 24 months in the Incremental PD group (p < 0.001) and from 1.38 ± 0.61 L/day to 0.71 ± 0.46 L/day in the Full-dose PD group (p < 0.001). There was no difference in the slope of UV decline between Incremental and Full-dose PD (p = 0.18).
Compared with Full-dose PD start, Incremental PD start is associated with similar declines in RKF and UV.

The wave of kidney and heart outcome trials, showing multiple potential benefits for sodium-glucose co-transport 2 (SGLT2) inhibitors, have excluded patients with an estimated glomerular filtration rate below 25 ml/min/1.73 m2. However, dialysis patients are at the highest risk of cardiovascular disease and would benefit most from effective cardioprotective therapies. There is emerging evidence from experimental studies and post hoc analyses of randomised clinical trials that SGLT2 inhibitors are well tolerated and may also be effective in preventing cardiovascular and mortality outcomes in patients with severe chronic kidney disease, including patients receiving dialysis. As such, extending the usage of SGLT2 inhibitors to dialysis patients could provide a major advancement in their care. Peritoneal dialysis (PD) patients have an additional unmet need for effective pharmacotherapy to preserve their residual kidney function (RKF), with its associated mortality benefits, and for treatment options that help reduce the risk of transfer to haemodialysis. Experimental data suggest that SGLT2 inhibitors, via various mechanisms, may preserve RKF and protect the peritoneal membrane. There is sound physiological rationale and an urgent clinical need to execute robust randomised control trials to study the use of SGLT2 inhibitors in PD patients to answer important questions of relevance to patients and healthcare systems.

UNASSIGNED: Previous research on incremental hemodialysis transition has mainly focused on one or two benefits or prognoses. We aimed to conduct a comprehensive analysis by investigating whether incremental hemodialysis was simultaneously associated with adequate dialysis therapy, stable complication indicators, long-lasting arteriovenous vascular access, and long-lasting preservation of residual kidney function (RKF) without increasing mortality or hospitalization.
UNASSIGNED: Incident hemodialysis patients from Huashan Hospital in Shanghai, China, over the period of 2012 to 2019, were enrolled and followed every three months until death or the time of censoring. Changes in complication indicators from baseline to all post-baseline visits were analyzed by mixed-effects models. The outcomes of RKF loss, arteriovenous vascular access complications, and the composite of all-cause mortality and cardiovascular events were compared between incremental and conventional hemodialysis by Cox proportional hazards model.
UNASSIGNED: Of the 113 patients enrolled in the study, 45 underwent incremental and 68 conventional hemodialysis. There were no significant differences in the changes from baseline to post-baseline visits in complication indicators between the two groups. Incremental hemodialysis reduced the risks of RKF loss (HR, 0.33; 95% CI, 0.14-0.82), de novo arteriovenous access complication (HR, 0.26; 95% CI, 0.08-0.82), and recurrent arteriovenous access complications under the Andersen-Gill (AG) model (HR, 0.27; 95% CI, 0.10-0.74) and the Prentice, Williams and Peterson Total Time (PWP-TT) model (HR, 0.31; 95% CI, 0.12-0.80). There were no significant differences in all-cause hospitalization or the composite outcome between groups.
UNASSIGNED: Incremental hemodialysis is an effective dialysis transition strategy that preserves RKF and arteriovenous access without affecting dialysis adequacy, patient stability, hospitalization risk and mortality risk. Randomized controlled trials are warranted.

Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.

BACKGROUND: Fluid overload and sleep apnea (SA) are known risk factors for mortality in dialysis patients. Although incidence and severity of SA were shown higher in peritoneal dialysis (PD) patients than in hemodialysis patients, data regarding the association of SA with body fluid status and mortality are limited. Therefore, the association of SA with body fluid status and mortality were investigated in a prospective cohort with patients undergoing PD.
METHODS: The present study included 103 prevalent PD patients who were followed up for median 70 months. At baseline, the subjects underwent in-home polysomnography, bioelectrical impedance analysis, and urea kinetics. Excessive daytime sleepiness and sleep quality were assessed using sleep questionnaires. SA was defined as apnea/hypopnea index higher than 15 events per hour.
RESULTS: Sleep apnea was diagnosed in 57 (55.3%) patients (SA group); the subjects had significantly higher extracellular water (10.3 ± 1.4 vs. 9.2 ± 1.8, p = 0.001) and lower residual kidney function (RKF) (3.3 ± 3.3 vs. 5.9 ± 7.2, p = 0.02) compared with subjects in the non-SA group. SA was significantly associated with RKF [odds ratio, 0.84; 95% confidence interval (CI), 0.73-0.97] in multivariable logistic regression analysis. In multivariable Cox regression models, SA was a significant predictor of mortality in PD patients (adjusted hazard ratio, 5.74; 95% CI, 1.09-30.31) after adjusting for well-known risk factors.
CONCLUSIONS: Sleep apnea was very common in PD patients and significantly associated with lower RKF. SA was also a novel risk predictor of mortality in PD patients.

BACKGROUND: Residual kidney function (RKF) provides substantial volume and solute clearance even after dialysis initiation. Preservation of RKF is associated with improved outcomes including mortality in patients on both peritoneal and haemodialysis (HD). Factors predicting RKF loss are unclear, including HD modality. Nocturnal haemodialysis (NHD) may result in less aggressive fluid and solute shifts, however, retrospective data suggests frequent NHD may accelerate RKF decline. The aim of the study was to determine if decline in RKF differs between patients undergoing conventional haemodialysis (CHD) versus NHD.
METHODS: A prospective observational study of incident HD patients was undertaken comparing patients undertaking CHD (4-5 h, 3 days/week) and NHD (8 h, 3-5 nights/week). Change in RKF was measured by urea and creatinine clearance (48-h interdialytic urine collection) and glomerular filtration rate (GFR) (Cr51-EDTA nuclear scan) at initiation of dialysis (baseline) and 12 months.
RESULTS: A total of 18 incident HD patients were recruited (8 CHD, 10 NHD). Three patients withdrew after baseline (n = 15). Baseline RKF was similar between groups with mean nuclear GFR of 13.3 ± 4.1 mL/min in the CHD cohort vs 13.5 ± 4.6 mL/min in the NHD group (p = 0.89). Baseline urine volume was 2399 ± 950 mLs and 2794 ± 1662 mLs in the CHD and NHD, respectively (p = 0.57). Nuclear GFR declined from time 0 to 12 months to 9.3 ± 2.5 mL/min and 10.4 ± 4.3 mL/min in the CHD and NHD, respectively (p = 0.52). There was a significant decline in 48-h urine volume over 12 months with a mean volume of 1943 ± 1087.0 mLs in the CHD compared to 601.7 ± 315.3 mLs in the NHD (p = 0.01). No significant difference was found in other measures of RKF between groups over 12 months.
CONCLUSIONS: This small prospective cohort study found that the loss of residual urine volume was greater in the NHD vs the CHD cohort but there was no difference in other measures of RKF.

OBJECTIVE: Bioimpedance spectroscopy (BIS) allows volume status to be assessed objectively. This study evaluated the effect of BIS-guided fluid management on residual kidney function (RKF), volume status, and cardiovascular events in peritoneal dialysis (PD) patients.
METHODS: A multicenter, prospective, randomized, controlled trial was conducted over 12 months in 2013-2017. Non-anuric PD patients (urine volume ≥ 500 mL/day) were randomized to clinical method-guided management (n = 98) or BIS-guided management (n = 103). The volume in the BIS group was controlled with BIS, with the aim of achieving the target overhydration (OH) goal of -2.0 to +2.0 L. The volume in the control group was controlled by clinical assessment alone. The groups were compared in terms of change in RKF and volume status at 12 months relative to baseline and in terms of cardiovascular event rates during a median follow-up period of 36 months.
RESULTS: Compared with the controls, the BIS group did not show a significant improvement in change in OH, after adjustments were made for covariates (P = 0.191). The two groups did not differ in terms of delta OH, renal creatinine and urea clearance, and 24 h urine volume. The control and BIS groups also did not differ significantly in terms of change in peritoneal ultrafiltration volume, blood pressure, body weight and echocardiographic variables or in cardiovascular event rates (10.2% vs 11.3%; P = 0.953).
CONCLUSIONS: Bioimpedance spectroscopy-guided fluid management did not show an additional benefit to achieve euvolemia, and did not affect the decline in RKF in non-anuric PD patients.

BACKGROUND: Although angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U.S.
METHODS: We conducted a retrospective observational cohort study using the US Renal Data System and electronic health records data from a large national dialysis provider. We identified adult patients who initiated PD from 2007 to 2011. Only patients who participated in the federal prescription drug benefit program, Medicare Part D, for the first 90 days of dialysis were included. Patients who filled a prescription for an ACEI or ARB during those 90 days were considered users. We applied Cox proportional hazards models to an inverse probability of treatment-weighted (IPTW) cohort to estimate the hazard ratio (HR) for anuria (24-h urine volume < 200 ml) in ACEI/ARB users vs. non-users.
RESULTS: Among 886 patients, 389 (44%) used an ACEI/ARB. Almost a third of these patients were black or Hispanic, and more than a quarter had comorbidities that would have excluded them from the randomized clinical trials of ACEI/ARB. Two hundred eighty patients reached anuria over 840 person-years of follow-up, for a composite event rate of 33 events per 100 person-years. We found no clear association between ACEI/ARB use and progression to anuria [HR: 0.86, 95% CI: 0.73-1.02].
CONCLUSIONS: ACEI/ARB use is common in patients initiating PD in the U.S. but was not associated with a lower risk of anuria. Residual confounding by unmeasured variables is an important limitation of this observational study. Still, these findings suggest that pragmatic clinical trials are warranted to test the effectiveness of ACEI/ARB in slowing the decline of residual kidney function in a diverse population of peritoneal dialysis patients with multiple comorbid conditions.