Impact of incremental initiation of haemodialysis on mortality: a systematic review and meta-analysis.

BACKGROUND: Incremental haemodialysis initiation entails lower sessional duration and/or frequency than the standard 4 h thrice-weekly approach. Dialysis dose is increased as residual kidney function (RKF) declines. This systematic review evaluates its safety, efficacy and cost-effectiveness. METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library databases from inception to 27 February 2022. Eligible studies compared incremental haemodialysis (sessions either fewer than three times weekly or of duration <3.5 h) with standard treatment. The primary outcome was mortality. Secondary outcomes included treatment-emergent adverse events, loss of RKF, quality of life and cost effectiveness. The study protocol was prospectively registered. Risk of bias assessment used the Newcastle-Ottawa Scale and the revised Cochrane risk of bias tool, as appropriate. Meta-analyses were undertaken in Review Manager, Version 5.4. RESULTS: A total of 644 records were identified. Twenty-six met the inclusion criteria, including 22 cohort studies and two randomized controlled trials (RCTs). Sample size ranged from 48 to 50 596 participants (total 101 476). We found no mortality differences (hazard ratio = 0.99; 95% CI 0.80-1.24). Cohort studies suggested similar hospitalization rates though the two small RCTs suggested less hospitalization after incremental initiation (relative risk = 0.31; 95% CI 0.18-0.54). Data on other treatment-emergent adverse events and quality of life was limited. Observational studies suggested reduced loss of RKF in incremental haemodialysis. This was not supported by RCT data. Four studies reported reduced costs of incremental treatments. CONCLUSIONS: Incremental initiation of haemodialysis does not confer greater risk of mortality compared with standard treatment. Hospitalization may be reduced and costs are lower.

Outcomes of incident patients treated with incremental haemodialysis as compared with standard haemodialysis and peritoneal dialysis.

BACKGROUND: Residual kidney function is considered better preserved with incremental haemodialysis (I-HD) or peritoneal dialysis (PD) as compared with conventional thrice-weekly HD (TW-HD) and is associated with improved survival. We aimed to describe outcomes of patients initiating dialysis with I-HD, TW-HD or PD. METHODS: We conducted a retrospective analysis of a prospectively assembled cohort in a single university centre including all adults initiating dialysis from January 2013 to December 2020. Primary and secondary endpoints were overall survival and hospitalization days at 1 year, respectively. RESULTS: We included 313 patients with 234 starting on HD (166 TW-HD and 68 I-HD) and 79 on PD. At the end of the study, 10 were still on I-HD while 45 transitioned to TW-HD after a mean duration of 9.8 ± 9.1 months. Patients who stayed on I-HD were less frequently diabetics (P = .007). Mean follow-up was 33.1 ± 30.8 months during which 124 (39.6%) patients died. Compared with patients on TW-HD, those on I-HD had improved survival (hazard ratio 0.49, 95% confidence interval 0.26-0.93, P = .029), while those on PD had similar survival. Initial kidney replacement therapy modality was not significantly associated with hospitalization days at 1 year. CONCLUSIONS: I-HD is suitable for selected patients starting dialysis and can be maintained for a significant amount of time before transition to TW-HD, with diabetes being a risk factor. Although hospitalization days at 1 year are similar, initiation with I-HD is associated with improved survival as compared with TW-HD or PD. Results of randomized controlled trials are awaited prior to large-scale implementation of I-HD programmes.

Initiating haemodialysis twice-weekly as part of an incremental programme may protect residual kidney function.

BACKGROUND: Initiating twice-weekly haemodialysis (2×HD) in patients who retain significant residual kidney function (RKF) may have benefits. We aimed to determine differences between patients initiated on twice- and thrice-weekly regimes, with respect to loss of kidney function, survival and other safety parameters. METHODS: We conducted a single-centre retrospective study of patients initiating dialysis with a residual urea clearance (KRU) of ≥3 mL/min, over a 20-year period. Patients who had 2×HD for ≥3 months during the 12 months following initiation of 2×HD were identified for comparison with those dialysed thrice-weekly (3×HD). RESULTS: The 2×HD group consisted of 154 patients, and the 3×HD group 411 patients. The 2×HD patients were younger (59 ± 15 versus 62 ± 15 years: P = 0.014) and weighed less (70 ± 16 versus 80 ± 18 kg: P < 0.001). More were females (34% versus 27%: P = 0.004). Fewer had diabetes (25% versus 34%: P = 0.04) and peripheral vascular disease (PVD) (13% versus 23%: P = 0.008). Baseline KRU was similar in both groups (5.3 ± 2.4 for 2 × HD versus 5.1 ± 2.8 mL/min for 3 × HD: P = 0.507). In a mixed effects model correcting for between-group differences in comorbidities and demographics, 3×HD was associated with increased rate of loss of KRU and separation of KRU. In separate mixed effects models, group (2×HD versus 3×HD) was not associated with differences in serum potassium or phosphate, and the groups did not differ with respect to total standard Kt/V. Survival, adjusted for age, gender, weight, baseline KRU and comorbidity (prevalence of diabetes, cardiac disease, PVD and malignancy) was greater in the 2×HD group (hazard ratio 0.755: P = 0.044). In sub-analyses, the survival benefit was confined to women, and those of less than median bodyweight. CONCLUSION: 2×HD initiation as part of an incremental programme with regular monthly monitoring of KRU was safe and associated with a reduced rate of loss of RKF early after dialysis initiation and improved survival. Randomized controlled trials of this approach are indicated.

Incremental and twice weekly haemodialysis in Australia and New Zealand.

BACKGROUND: Haemodialysis is usually started at a frequency of three times a week, with occasional patients starting twice weekly ('incremental dialysis'). Incremental haemodialysis (HD) may preserve residual kidney function and has been associated with reduced mortality. In the present study, we report prevalence and outcomes of incremental dialysis in Australia and New Zealand. METHODS: The cohort was all adults starting renal replacement therapy with HD in Australia and New Zealand 2004-2015. We used cox proportional hazards modelling with a primary exposure of dialysis frequency at first survey date (≥ or <3 times per week). The primary outcome was all-cause mortality (primary), cardiovascular and non-cardiovascular mortality (secondary). RESULTS: Eight-hundred fifty of 27 513 subjects were started on twice weekly HD (prevalence 3%). Compared to conventional patients, incremental dialysis patients were older (67 vs 62 years, P < 0.001), had a lower body mass index (26.1 vs 27.7 kg/m2 , P < 0.001), had a higher starting estimated glomerular filtration rate (7.59 vs 6.66 mL/min P < 0.001) and had less diabetes (39.2% vs 50.2%, P < 0.001). In a multivariate model, incremental start dialysis was not associated with all-cause mortality (hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 0.92-1.16) or cardiovascular mortality (HR = 0.87, 95% CI = 0.71-1.07), but was associated with an increased risk of non-cardiovascular mortality (HR = 1.25, 95% CI = 1.11-1.42). CONCLUSION: Incremental dialysis was used infrequently, and there was evidence of patient level differences. All-cause mortality was similar, but there were differences in cause specific mortality. Incremental dialysis needs to be tested in prospective trials to define the safety and efficacy of this approach.

Comparison between incremental and thrice-weekly haemodialysis: Systematic review and meta-analysis.

AIM: Incremental haemodialysis (HD) regimen has recently gained attention. However, its efficacy and safety, compared with conventional thrice-weekly HD, are controversial and previous research results are not convincing. We sought to conduct a meta-analysis to evaluate the benefits and limitations of incremental HD regimen in patients with end-stage renal disease. METHODS: We searched PubMed, Embase, and the Cochrane Central Register databases for controlled trials published until January 2017. Outcomes of interest included baseline patient characteristics, mortality risk, renal function, urine volume, laboratory values, and hospitalization rate. RESULTS: Overall, 16 studies (n = 252 330), including 15 observational studies and 1 cross-sectional study, were included. Incremental HD reduced mortality risk, compared with conventional HD (risk ratio [RR], 0.797; 95% confidence interval [CI], 0.731-0.870; P < 0.001; I2 = 0%). Renal function (standardized mean difference [SMD] = 0.677, 95% CI: 0.035 to 1.318, P = 0.039; I2 = 92.7%) and urine volume (weighted mean difference [WMD] = 333.37, 95% CI: 86.81 to 579.93, P = 0.008; I2 = 92.7%) were also better preserved in patients on incremental HD. Other clinical outcomes, including serum levels of calcium, phosphate, albumin, haemoglobin, and hospitalization rate, were similar between groups. CONCLUSION: An incremental therapeutic approach as a beginning haemodialysis regimen is associated with lower mortality and better preservation of greater residual renal function.

IHDIP: a controlled randomized trial to assess the security and effectiveness of the incremental hemodialysis in incident patients.

BACKGROUND: Most people who make the transition to renal replacement therapy (RRT) are treated with a fixed dose thrice-weekly hemodialysis réegimen, without considering their residual kidney function (RKF). Recent papers inform us that incremental hemodialysis is associated with preservation of RKF, whenever compared with conventional hemodialysis. The objective of the present controlled randomized trial (RCT) is to determine if start HD with one sessions per week (1-Wk/HD), it is associated with better patient survival and other safety parameters. METHODS/DESIGN: IHDIP is a multicenter RCT experimental open trial. It is randomized in a 1:1 ratio and controlled through usual clinical practice, with a low intervention level and non-commercial. It includes 152 incident patients older than 18 years, with a RRF of ≥4 ml/min/1.73 m2, measured by renal clearance of urea (KrU). The intervention group includes 76 patients who will start with incremental HD (1-Wk/HD). The control group includes 76 patients who will start with thrice-weekly hemodialysis régimen. The primary outcome is assessing the survival rate, while the secondary outcomes are the morbidity rate, the clinical parameters, the quality of life and the efficiency. DISCUSSION: This study will enable to know the number of sessions a patient should receive when starting HD, depending on his RRF. The potentially important clinical and financial implications of incremental hemodialysis warrant this RCT. TRIAL REGISTRATION: U.S. National Institutes of Health, ClinicalTrials.gov . Number: NCT03239808 , completed 13/04/2017. SPONSOR: Foundation for Training and Research of Health Professionals of Extremadura.

The importance of residual kidney function in haemodialysis patients.

In contrast to peritoneal dialysis, residual kidney function (RKF) is commonly disregarded for haemodialysis (HD) patients and not regularly monitored or taken into account in routine clinical care. This is despite evidence that higher levels of RKF in HD patients are associated with better outcomes, including survival, total solute clearance, nutrition, inflammation and fluid balance. This review aims to summarise the clinical effects of RKF specifically in HD patients. Some level of RKF is present in over 80% of patients at the time of dialysis initiation, and while this declines over time, up to 30% of patients on HD for 5 years still have a measurable level of native kidney function. There is little evidence on how best to preserve RKF in HD patients, although it has been observed that intensive HD regimens in incident HD patients appear to accelerate RKF decline. RKF is not commonly factored into HD prescription and measures of adequacy, despite the fact that some guidelines such as Kidney Disease Outcomes Quality Initiative (KDOQI) and European Best Practice Guidelines suggest that it is reasonable to do so. This likely relates, at least in part, to perceived concerns regarding the inconvenience of timed urine collections and to the complexity and lack of consensus regarding the methods for integrating the intermittent clearance of HD with the continuous clearance of native renal function. Further research is required into how best to maintain and maximise the benefits of RKF in HD patients.

Dialysis for older adults: why should the targets be different?

The number of patients aged > 75-years treated by dialysis continues to increase, particularly in developed countries. Haemodialysis is a well-established treatment with national and international clinical guidelines designed to provide patients with optimal treatment. However, these were developed when the dialysis population was younger, and less co-morbid. This change in patient demographics questions whether these guideline targets still apply to older patients. More patients now start dialysis with residual kidney function and could benefit from a less frequent dialysis schedule. Older patients have a lower thirst drive, so lower interdialytic gains, reduced appetite, muscle mass and physical activity would potentially allow starting dialysis with less frequent sessions a practical option. Similarly, patients with residual kidney function and lower metabolic activity may not need to meet current dialyser Kt/Vurea clearance targets to remain healthy. Instead, some elderly patients may be at risk of malnutrition and might need liberalisation of the low salt, potassium and phosphate dietary restrictions, or even additional supplements to ensure adequate protein intake. Although a fistula is the preferred vascular access, a forearm fistula may not be an option due to vascular disease, while a brachial fistula can potentially compromise cardiovascular reserve, so a dialysis catheter becomes the de facto access, especially in patients with limited life expectancy. Thus, clinical guideline targets designed for a younger less co-morbid dialysis population may not be equally applicable to the older patient initiating dialysis, and so a more individualised approach to dialysis prescription and vascular access is required.

Incremental versus conventional haemodialysis in end-stage kidney disease: a systematic review and meta-analysis.

Background: Appropriate dialysis prescription in the transitional setting from chronic kidney disease to end-stage kidney disease is still challenging. Conventional thrice-weekly haemodialysis (HD) might be associated with rapid loss of residual kidney function (RKF) and high mortality. The benefits and risks of incremental HD compared with conventional HD were explored in this systematic review and meta-analysis. Methods: We searched MEDLINE, Scopus and Cochrane Central Register of Controlled Trials up to April 2023 for studies that compared the impacts of incremental (once- or twice-weekly HD) and conventional thrice-weekly HD on cardiovascular events, RKF, vascular access complications, quality of life, hospitalization and mortality. Results: A total of 36 articles (138 939 participants) were included in this meta-analysis. The mortality rate and cardiovascular events were similar between incremental and conventional HD {odds ratio [OR] 0.87 [95% confidence interval (CI)] 0.72-1.04 and OR 0.67 [95% CI 0.43-1.05], respectively}. However, hospitalization and loss of RKF were significantly lower in patients treated with incremental HD [OR 0.44 (95% CI 0.27-0.72) and OR 0.31 (95% CI 0.25-0.39), respectively]. In a sensitivity analysis that included studies restricted to those with RKF or urine output criteria, incremental HD had significantly lower cardiovascular events [OR 0.22 (95% CI 0.08-0.63)] and mortality [OR 0.54 (95% CI 0.37-0.79)]. Vascular access complications, hyperkalaemia and volume overload were not statistically different between groups. Conclusions: Incremental HD has been shown to be safe and may provide superior benefits in clinical outcomes, particularly in appropriately selected patients. Large-scale randomized controlled trials are required to confirm these potential advantages.

Incremental dialysis: two complementary views.

Franco Casino and Mariana Murea discuss today's knowledge about the 'incremental dialysis' concept. Franco Casino frames the problem by saying that, in the presence of substantial residual kidney function, kidney replacement therapy can begin with low doses and/or frequencies, to be gradually increased to compensate for any subsequent losses of residual kidney function, keeping the total clearance above the minimum levels of adequacy. He remarks that studies so far have documented that this approach is safe. He recognizes that adequate randomized controlled trials (RCTs) are necessary to confirm the safety and simplify and standardize the practical aspects of this approach. Mariana Murea objects that most of the evidence gathered so far primarily derives from retrospective and observational studies, which can be influenced by socioeconomic constraints. She argues for the need for RCTs to provide compelling empirical evidence on the efficacy of incremental dialysis. Nephrologists are still reluctant to adopt this approach for various reasons, including unfamiliarity with the method, lack of practical guidance and financial disincentives. Several countries have ongoing or planned RCTs comparing incremental dialysis with conventional dialysis. These trials can shift the haemodialysis paradigm if they validate the safety and effectiveness of this approach. The moderators believe that the results of ongoing trials must be carefully interpreted, and further validation may be needed across different patient populations or healthcare settings. The ultimate goal is to gather robust evidence that could lead to widespread adoption of incremental haemodialysis, optimizing treatment, reducing overtreatment, preserving resources and improving patients' quality of life.

Could incremental haemodialysis be a new standard of care? A suggestion from a long-term observational study.

Introduction: The term incremental haemodialysis (HD) means that both dialysis dose and frequency can be low at dialysis inception but should be progressively increased, to compensate for any subsequent reduction in residual kidney function. Policy of the Matera Dialysis Center is to attempt an incremental start of HD without a strict low-protein diet in all patients choosing HD and with urine output (UO) >500 ml/day. The present study aimed at analyzing the results of this policy over the last 20 years. Subjects and methods: The dataset of all patients starting HD between January 1st, 2000 and December 31st, 2019 was retrieved from the local electronic database. Exclusion criteria were: urine output <500 ml/day or follow-up <3 months after the start of the dialysis treatment. Results: A total of 266 patients were retrieved; 64 of them were excluded from the study. The remaining 202 patients were enrolled into the study and subdivided into 3 groups (G1, G2 and G3) according to the frequency of treatment at the start of dialysis: 117 patients (57.9%) started with once-a-week (1HD/wk) (G1); 46 (22.8%) with twice-a-week (2HD/wk) (G2); 39 (19.3%) with thrice-a-week (3HD/wk) dialysis regimen (G3). Patients of G1 remained on 1HD/wk for 11.9 ±14.8 months and then transferred to 2HD/wk for further 13.0 ±20.3 months. Patients of G2 remained on 2HD/wk for 16.7 ±23.2 months. Altogether, 25943 sessions were administered during the less frequent treatment periods instead of 47988, that would have been delivered if the patients had been on 3HD/wk, thus saving 22045 sessions (45.9%). Gross mortality of the entire group was 12.6%, comparable to the mean mortality of the Italian dialysis population (16.2%). Survival at 1 and 5 years was not significantly different among the 3 groups: 94% and 61% (G1); 83% and 39% (G2); 84% and 46% (G3). Conclusions: Our long-term observational study suggests that incremental HD is a valuable option for incident patients. For most of them (80.7%) it is viable for about 1-2 years, with obvious socio-economic benefits and survival rates comparable to that of the Italian dialysis population. However, randomized controlled trials are lacking and therefore urgently needed. If they will confirm observational data, incremental HD will be a new standard of care.

The lacking equation that estimates the protein catabolic rate in patients on once-weekly haemodialysis.

BACKGROUND: The normalized protein catabolic rate (PCRn) is one of the key indices derived from the urea kinetic model (UKM) in haemodialysis (HD) patients. Ideally, it should be assessed using the double pool UKM (KDOQI clinical practice guidelines, AIKD, 2015), as the web-based software Solute-Solver (SS) does (Daugirdas et al., AJKD, 2009). Simple formulae exist to compute PCRn for patients on thrice- or twice-weekly HD schedule, but not for patients on once-weekly HD schedule (1HD/wk). Aim of the present technical note was to introduce the lacking equation that estimates PCRn in the 1HD/wk regimen. METHODS: Data of a single HD session associated to monthly UKM studies were retrieved from the electronic database of our dialysis unit for 80 historical patients on 1HD/wk regimen. The UKM parameters, as calculated with SS, were used in a subgroup of 40 randomly selected patients (group 1) to build-up a multiple regression model of PCRn. The latter was used to predict PCRn (PCRnPred) values in the cohort of the remaining 40 patients (group 2). The Bland-Altman plot was used to analyse the agreement between PCRnPred and the paired "observed" (PCRnObs) values, as measured with SS. RESULTS: The following equation was established by means of the multiple regression analysis: PCRn = - 0.46 + 0.01 × C0 + 0.09 × eKt/V + 3.94 × Kru/V, where C0 is pre-dialysis blood urea nitrogen concentration, eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. The PCRnPred values were 0.99 ± 0.24 g/kg/day; the PCRnObs values were 0.96 ± 0.23 g/kg/day (mean difference 0.03 ± 0.05 g/kg/day). Their difference at the Bland-Altman analysis ranged from - 0.08 to + 0.13 g/kg/day. Finally, a nomogram was drawn: it can be used to estimate not only PCRn from Kru/V and C0, but also C0 as a function of Kru/V and PCRn. CONCLUSIONS: The equation here introduced allows a simple and accurate estimate of PCRn in patients on once-weekly HD regimen. The availability of the nomogram relating C0 to PCRn and Kru/V could be a further step to make safer and safer the once-weekly HD regimen. The following equation was established by means of the multiple regression analysis [Formula: see text] where PCRn is the normalized protein catabolic rate (PCRn), C0 is pre-dialysis blood urea nitrogen concentration (BUN), eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. A nomogram relating pre-dialysis BUN to PCRn and Kru/V could be drawn: it can be used to estimate not only PCRn from Kru/V and pre-dialysis BUN, but also pre-dialysis BUN as a function of Kru/V and PCRn.

Improving the "second generation Daugirdas equation" to estimate Kt/V on the once-weekly haemodialysis schedule.

INTRODUCTION: The haemodialysis (HD) dose, as expressed by Kt/V urea, is currently routinely estimated with the second generation Daugirdas (D2) equation (Daugirdas in J Am Soc Nephrol 4:1205-1213, 1993). This equation, initially devised for a thrice-weekly schedule, was modified to be used for all dialysis schedules (Daugirdas et al. in Nephrol Dial Transplant 28:2156-2160, 2013), by adopting a variable factor that adjusts for the urea generation (GFAC) over the preceding inter-dialysis interval (PIDI, days). This factor was set at 0.008 for the mid-week session of the standard thrice-weekly HD schedule. In theory, by setting PIDI = 7, one could get GFAC = 0.0025, to be used in patients on the once-weekly (1HD/wk) schedule, but actually this has never been tested. Moreover, GFAC was derived not taking into account the residual kidney urea clearance (Kru). Aim of the present study was to provide a specific value of GFAC for patients on  a once-weekly hemodialysis schedule. SUBJECTS AND METHODS: The equation to predict GFAC (GFAC-1) in the 1HD/wk schedule was established in a group of 80 historical Italian patients (group 1) and validated in a group of 100 historical Spanish patients (group 2), by comparing the Kt/V computed using GFAC-1 (Kt/VGFAC-1) with the reference Kt/V (Kt/VSS) values, as computed with the web-based Solute-Solver software (SS) (Daugirdas et al. in Am J Kidney Dis 54:798-809, 2009). Three more sets of Kt/V (Kt/V0.008, Kt/V0.0025 and Kt/V0.0035) values were computed using the GFAC of the original D2 equation (0.008), the GFAC predicted by PIDI/7 (0.0025) and the mean observed GFAC-1 (0.0035), respectively. They were compared with the reference Kt/VSS values. RESULTS: The predicting equation obtained from group 1 was: GFAC-1 = 0.0022 + 0.0105 × Kru/V (R2 = 0.93). Mean Kt/VSS in the group 2 was 1.54 ± 0.29 SD (N = 500 HD sessions). The mean percent differences for Kt/V0.008, Kt/V0.0025, Kt/VGFAC-1, and Kt/V0.0035 were 5.1 ± 1.0%, - 1.4 ± 0.7%, 0.0 ± 0.3%, - 0.3 ± 0.7%, respectively. No statistically significant difference was found between Kt/V values, except for Kt/V0.008. CONCLUSION: A linear relationship was found between GFAC and Kru/V in patients on the 1HD/wk schedule. Such a relationship is able to improve the "second generation Daugirdas equation" for an accurate estimate of the single pool Kt/V in this setting. However, a simple replacement in the D2 equation of 0.008 with the mean observed GFAC (0.0035) could suffice in the clinical practice.

Routine assessment of kidney urea clearance, dialysis dose and protein catabolic rate in the once-weekly haemodialysis regimen.

BACKGROUND: The dialysis dose (Kt/V) and normalized protein catabolic rate (PCRn) are the most useful indices derived from the urea kinetic model (UKM) in haemodialysis (HD) patients. The kidney urea clearance (Kru) is another important UKM parameter which plays a key role in the prescription of incremental HD. Ideally, the three kinetic parameters should be assessed using the complex software Solute Solver based on the double pool UKM. In the clinical setting, however, the three indices are estimated with simplified formulae. The recently introduced software SPEEDY assembles the aforementioned equations in a plain spreadsheet, to produce quite accurate results of Kru, Kt/V and PCRn. Unfortunately, specific equations to compute Kt/V and PCRn for patients on a once-weekly HD regimen (1HD/wk) were not available at the time SPEEDY was built-up. We devised a new version of SPEEDY (SPEEDY-1) and an even simpler variant (SPEEDY-1S), using two recently published equations for the 1HD/wk schedule . Moreover, we also added a published equation to estimate the equivalent renal clearance (EKR) normalized to urea distribution volume (V) of 35 L (EKR35) from Kru and Kt/V . Aim of the present study was to compare the results obtained using the new methods (SPEEDY-1 and SPEEDY-1S) with those provided by the reference method Solute Solver. SUBJECTS AND METHODS: One hundred historical patients being treated with the once-weekly HD regimen were enrolled. A total of 500 HD sessions associated to the availability of monthly UKM studies were analysed in order to obtain Kru, single pool Kt/V (spKt/V), equilibrated Kt/V (eKt/V), V, PCRn and EKR35 values by using Solute Solver, SPEEDY-1 and SPEEDY-1S. RESULTS: When comparing the paired values of the above UKM parameters, as computed by SPEEDY-1 and Solute Solver, respectively, all differences but one were statistically significant at the one-sample t-test; however, the agreement limits at Bland-Altman analysis showed that all differences were negligible. When comparing the paired values of the above UKM parameters, as computed by SPEEDY-1S and Solute Solver, respectively, all differences were statistically significant; however, the agreement limits showed that the differences were negligible as far as Kru, spKt/V and eKt/V are concerned, though much larger regarding V, PCRn and EKR35. CONCLUSIONS: We implemented SPEEDY with a new version specific for the once-weekly HD regimen, SPEEDY-1. It provides accurate results and is presently the best alternative to Solute Solver. Using SPEEDY-1S led to a larger difference in PCRn and EKR35, which could be acceptable for clinical practice if SPEEDY-1 is not available.

Initiating renal replacement therapy through incremental haemodialysis: Protocol for a randomized multicentre clinical trial.

BACKGROUND: Thrice-weekly haemodialysis is the usual dose when starting renal replacement therapy; however, this schedule is no longer appropriate since it does not consider residual renal function. Several reports have suggested the potential benefit of beginning haemodialysis less frequently and incrementally increasing the dose as the residual renal function decreases. However, all the data published so far are from observational studies. Thus, this clinical trial avoids any potential selection bias and will assess the possible benefits that have been observed in observational studies. METHODS/DESIGN: This report describes the study protocol of a randomized prospective multi-centre open-label clinical trial to evaluate whether starting renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than the standard thrice-weekly regimen. We also explore other clinical parameters, such as concentrations of uremic toxins, dialysis doses, control of anaemia, removal of medium-weight uremic toxins, nutritional status, quality of life, hospital admissions and mortality. Only incident haemodialysis patients who can maintain a urea clearance rate KrU ≥ 2.5 mL/min/1.73 m2 are eligible. Patient recruitment began on 1 January 2017 and will last for 2 years or until the required sample size has been recruited to ensure the established statistical power has been reached. The minimum follow-up period will be 1 year. Anuric patients with acute renal failure and patients who return to haemodialysis after a kidney transplant failure are excluded. It has been calculated that 44 patients should be recruited into each group to achieve a power of 80% in a two-sided comparison of means with a usual significance level of 0.05. A time-to-event analysis will estimate the probability of kidney function survival in both groups using the Kaplan-Meier method. Survival curves will be compared with log-rank tests. This survival analysis will be complemented with a proportional hazard model to estimate the hazard ratio of kidney function survival adjusted for any confounding factors. Analyses will be carried out in accordance with the intention-to-treat principle. DISCUSSION: The incremental initiation of dialysis may preserve residual renal function better than the conventional treatment, with similar or higher survival rates, as reported by observational studies. To our knowledge, this is the first clinical trial to evaluate whether initiating renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than beginning with the standard thrice-weekly regimen. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03302546. Registered on 5 October 2017.

Comparison of characteristics of centers practicing incremental vs. conventional approaches to hemodialysis delivery - postdialysis recovery time and patient survival.

INTRODUCTION: Conventional haemodialysis (HD) involves treatment times of around 4 hours thrice weekly, taking no account of residual kidney function (RKF). In incremental HD the frequency and duration of dialysis sessions are individualized according to RKF. There are no studies comparing these approaches. We utilized data from a recent multicenter study to compare patient characteristics and outcomes between a center practicing incremental HD and others using a conventional approach. METHODS: Seven hundred and nine patients attending for routine outpatient HD in five UK centers were studied. One center practiced incremental dialysis (n = 254) and four conventional HD (n = 455). Data collected included demographics, comorbidity, dialysis parameters, routine biochemistry and hematology, recovery time postdialysis, and Beck Depression Inventory-II score (BDI-II). Patients were followed for a minimum of 12 months. FINDINGS: Pre- and postdialysis BP, serum calcium and phosphate were higher in the incremental center, whilst sessional Kt/Vurea was lower (all P < 0.001), as was the proportion of patients with a mean postdialysis BP <100 mmHg (P = 0.011). Patients recovered from their HD session more quickly in the incremental center, with significantly more patients reporting recovery within 1 and 4 hours Short-term survival was significantly better in the incremental center both unadjusted and adjusted for age, gender, ethnicity, dialysis vintage, anuria, history of cancer, heart disease, diabetes mellitus, body mass index, serum albumin, BDI-II score, and sessional Kt/V. DISCUSSION: The association between incremental dialysis, shorter postdialysis recovery times and improved short-term survival may be related to reduced haemodynamic stress as a consequence of less intensive ultrafiltration and reduced length of dialysis sessions. Prospective studies are required to test this hypothesis.

Residual renal function in incremental haemodialysis.

BACKGROUND: Equivalent renal clearance (EKR) and standard clearance (stdK) are continuous-equivalent measures of urea clearance and include residual renal function (RRF), if calculated appropriately. RRF is qualitatively better than dialysis with equivalent urea clearance. Instructions for calculating stdKt/V (stdK scaled by urea distribution volume) and its target value (2.3) are presented in the Kidney Disease Outcomes Quality Initiative (KDOQI) 2015 guidelines. EKR targets have not been defined in the current guidelines. METHODS: The stdKt/V in the presence of RRF was calculated with the classic double-pool urea kinetic model and with the Daugirdas modification, which accentuates the renal contribution. The EKR/V (EKR scaled by urea distribution volume) was calculated with nominal and adjusted renal clearance (renal urea clearance multiplied by a weighting factor). New prescriptions with different continuous clearance targets were generated by a computer program. RESULTS: The contribution of RRF can be weighted flexibly in EKR/V by adjusting the renal clearance value. A new therapeutic index, EKR/V a (adjusted total EKR/V), was introduced. In 62 incremental dialysis sessions of 16 patients with a renal urea clearance (Kr) of over 1 mL/min, the Daugirdas stdKt/V was, on average, 7.5% higher than classic stdK/V and adjusted EKR/V was 14.4% higher than unadjusted EKR/V. CONCLUSIONS: The stdKt/V is not an optimal descriptor of haemodialysis urea clearance. With EKR/V, the role of RRF can be evaluated more sensibly. Using adjusted EKR/V as the target permits less frequent incremental dialysis.

Rationale and design of DiPPI: A randomized controlled trial to evaluate the safety and effectiveness of progressive hemodialysis in incident patients. / Justificación y diseño de DiPPI: un ensayo controlado aleatorizado para evaluar la seguridad y la efectividad de la hemodiálisis progresiva en pacientes incidentes.

INTRODUCTION: Progressive haemodialysis (HD) is a starting regime for renal replacement therapy (RRT) adapted to each patient's necessities. It is mainly conditioned by the residual renal function (RRF). The frequency of sessions with which patients start HD (one or two sessions per week), is lower than that for conventional HD (three times per week). Such frequency is increased (from one to two sessions, and from two to three sessions) as the RRF declines. METHODOLOGY/DESIGN: IHDIP is a multicentre randomised experimental open trial. It is randomised in a 1:1 ratio and controlled through usual clinical practice, with a low intervention level and non-commercial. It includes 152 patients older than 18 years with chronic renal disease stage 5 and start HD as RRT, with an RRF of ≥4ml/min/1.73m2, measured by renal clearance of urea (KrU). The intervention group includes 76 patients who will start with one session of HD per week (progressive HD). The control group includes 76 patients who will start with three sessions per week (conventional HD). The primary purpose is assessing the survival rate, while the secondary purposes are the morbidity rate (hospital admissions), the clinical parameters, the quality of life and the efficiency. DISCUSSION: This study will enable us to know, with the highest level of scientific evidence, the number of sessions a patient should receive when starting the HD treatment, depending on his/her RRF. TRIAL REGISTRATION: Registered at the U.S. National Institutes of Health, ClinicalTrials.gov under the number NCT03239808.

Quel pourrait être le futur de la prise en charge de la maladie rénale chronique en nutrition ?

The nutrition care of patients with chronic kidney disease (CKD) remains a central question which is permanently studied. The benefits of a dietary protein restriction are once again enlightened, either by reducing the urea found to be hyperglycemic, thus improving the peripheric insulin sensitivity, or by decreasing phosphorus and FGF23 hormone, whose reductions are respectively associated with nephroprotection and diminution of cardiovascular events. The numerous researches conducted on the gut microbiota also open promising avenues to better understand the role of this ecosystem in CKD. Finally, the interest in incremental haemodialysis is revived, results show it may be associated with less loss of proteins and preservation of residual kidney function. The development of a nutritional score, informative of survival prediction, also offers the possibility to ensure a better follow-up of patients.