OBJECTIVE: Chronic kidney disease and end-stage kidney disease (ESKD) are well-established risk factors for cardiovascular disease (CVD), the leading cause of mortality in the dialysis population. Conventional therapies, such as statins, blood pressure control, and renin-angiotensin-aldosterone system blockade, have inadequately addressed this cardiovascular risk, highlighting the unmet need for effective treatment strategies. Sodium-glucose transporter 2 (SGLT2) inhibitors have demonstrated significant renal and cardiovascular benefits among patients with type 2 diabetes, heart failure, or CKD at risk of progression. Unfortunately, efficacy data in dialysis patients is lacking as ESKD was an exclusion criterion for all major clinical trials of SGLT2 inhibitors. This review explores the potential of SGLT2 inhibitors in improving cardiovascular outcomes among patients with ESKD, focusing on their direct cardiac effects.
RESULTS: Recent clinical and preclinical studies have shown promising data for the application of SGLT2 inhibitors to the dialysis population. SGLT2 inhibitors may provide cardiovascular benefits to dialysis patients, not only indirectly by preserving the remaining kidney function and improving anemia but also directly by lowering intracellular sodium and calcium levels, reducing inflammation, regulating autophagy, and alleviating oxidative stress and endoplasmic reticulum stress within cardiomyocytes and endothelial cells. This review examines the current clinical evidence and experimental data supporting the use of SGLT2 inhibitors, discusses its potential safety concerns, and outlines ongoing clinical trials in the dialysis population. Further research is needed to evaluate the safety and effectiveness of SGLT2 inhibitor use among patients with ESKD.

UNASSIGNED: Longitudinal changes in residual kidney function have not been well-examined in patients starting chronic hemodialysis (HD).
UNASSIGNED: We analyzed urine volume and kidney solute clearances from timed urine collections and corresponding plasma samples from 42 patients randomized to incremental HD (n = 21) and conventional HD (n = 21) in the TwoPlus pilot study. Samples were collected before HD initiation (baseline); and at 6, 12, 24, and 48 weeks. We assessed temporal trends in urine volume, kidney urea and creatinine clearance, and correlations between urine volume and kidney solute clearance.
UNASSIGNED: Residual kidney function parameters in all patients declined over time; the pattern of decline differed between urine volume and kidney solute clearances. Urine volume declined at a steady rate with median (quartile 1, quartile 3) percentage change relative to baseline of -10% (-36 to 29) at week 6 and -47% (-76 to 5) by week 48. Kidney urea and creatinine clearances exhibited a larger decline than urine volume at week 6, -32% (-61 to 8) and -47% (-57 to -20), respectively. The rate of decline subsequently slowed, reaching about 61% decline for both solutes by week 48. Conventional HD demonstrated larger declines in urine volume and kidney urea clearance than incremental HD at week 6. Urine volume showed moderate correlation with urea (R = 0.47) and weaker correlation with creatinine (R = 0.34).
UNASSIGNED: Despite gradual decrement in urine volume and kidney solute clearances, residual kidney function persists nearly 1 year after HD initiation. This knowledge could motivate increased practice of individualizing HD prescriptions by incorporating residual kidney function.

OBJECTIVE: Incremental peritoneal dialysis (IPD) could decrease unfavorable glucose exposure results and preserve (RKF). However, there is no standardization of dialysis prescriptions for patients undergoing IPD. We designed a prospective observational multi-center study with a standardized IPD prescription to evaluate the effect of IPD on RKF, metabolic alterations, blood pressure control, and adverse outcomes.
METHODS: All patients used low GDP product (GDP) neutral pH solutions in both the incremental continuous ambulatory peritoneal dialysis (ICAPD) group and the retrospective standard PD (sPD) group. IPD patients started treatment with three daily exchanges five days a week. Control-group patients performed four changes per day, seven days a week.
RESULTS: A total of 94 patients (47 IPD and 47 sPD) were included in this study. The small-solute clearance and mean blood pressures were similar between both groups during follow-up. The weekly mean glucose exposure was significantly higher in sPD group than IPD during the follow-up (p < 0.001). The patients with sPD required more phosphate-binding medications compared to the IPD group (p = 0.05). The rates of peritonitis, tunnel infection, and hospitalization frequencies were similar between groups. Patients in the sPD group experienced more episodes of hypervolemia compared to the IPD group (p = 0.007). The slope in RKF in the 6th month was significantly higher in the sPD group compared to the IPD group (65% vs. 95%, p = 0.001).
CONCLUSIONS: IPD could be a rational dialysis method and provide non-inferior dialysis adequacy compared to full-dose PD. This regimen may contribute to preserving RKF for a longer period.

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UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: Residual kidney function (RKF) impacts patients\' survival rate and quality of life when undergoing peritoneal dialysis (PD). This meta-analysis was conducted to systematically identify risk and protective factors associated with RKF decline and loss.
UNASSIGNED: We searched three English and one Chinese databases from inception to January 31, 2023, for cohort and cross-sectional studies exploring factors associated with RKF decline or loss. The random effects model was employed to aggregate risk estimates and 95% confidence intervals (CIs) from multivariate analysis. Sensitivity and subgroup analyses were performed to explore the heterogeneity among the studies.
UNASSIGNED: Twenty-seven studies comprising 13549 individuals and 14 factors were included in the meta-analysis. Based on the meta-analysis results, risk factors involving male gender (hazard ratio (HR) 1.689, 95%CI 1.385-2.061), greater body mass index (BMI) (odds ratio (OR) 1.081, 95% confidence interval (CI) 1.029-1.135), higher systolic blood pressure (SBP) (HR 1.014, 95%CI 1.005-1.024), diabetes mellitus (DM) (HRRKF loss 1.873, 95%CI 1.475-2.378), DM (ORRKF decline 1.906, 95%CI 1.262-2.879), peritonitis (relative ratio (RR) 2.291, 95%CI 1.633-3.213), proteinuria (OR 1.223, 95%CI 1.117-1.338), and elevated serum phosphorus (RR 2.655, 95%CI 1.679-4.201) significantly contributed to the risk of RKF decline and loss in PD patients. Conversely, older age (HR 0.968, 95%CI 0.956-0.981), higher serum albumin (OR 0.834, 95%CI 0.720-0.966), weekly Kt/V urea (HR 0.414, 95%CI 0.248-0.690), baseline urine volume (UV) (HR 0.791, 95%CI 0.639-0.979), baseline RKF (HR 0.795, 95%CI 0.739-0.857) exhibited protective effects. However, diuretics use, automatic peritoneal dialysis (APD) modality and baseline RKF did not significantly impact RKF decline.
UNASSIGNED: Patients with male gender, greater BMI, higher SBP, DM, peritonitis, proteinuria, and elevated serum phosphorus might have a higher risk of RKF decline and loss. In contrast, older age, higher serum albumin, weekly Kt/V urea, baseline UV, and baseline RKF might protect against RKF deterioration.

UNASSIGNED: The survival benefit of residual kidney function (RKF) in patients on hemodialysis is presumably due to enhanced fluid management and solute clearance. However, data are lacking on the association of renal urea clearance (CLurea) with specific causes of death.
UNASSIGNED: We conducted a longitudinal cohort study of 39,623 adults initiating thrice-weekly in-center hemodialysis from 2007 to 2011 and had data on renal CLurea and urine volume. Multivariable cause-specific proportional hazards model was used to examine the associations between baseline RKF and cause-specific mortality, including sudden cardiac death (SCD), non-SCD cardiovascular death (CVD), and non-CVD. Restricted cubic splines were fitted for change in RKF over 6 months after initiating hemodialysis.
UNASSIGNED: Among 39,623 patients with data on baseline renal CLurea and urine volume, there was a significant trend toward a higher mortality risk across lower RKF levels, irrespective of cause of death in a case-mix adjustment model (Ptrend < 0.05). Adjustment for ultrafiltration rate (UFR) slightly attenuated the association between low renal CLurea and high cause-specific mortality, whereas adjustment for highest potassium did not have substantial effect. Among 12,169 patients with data on change in RKF, a 6-month decline in renal CLurea showed graded associations with SCD, non-SCD CVD, and non-CVD risk, whereas the graded associations between faster 6-month decline in urine output and higher death risk were clear only for SCD and non-CVD.
UNASSIGNED: Lower RKF and loss of RKF were associated with higher cause-specific mortality among patients initiating thrice-weekly in-center hemodialysis.

Residual kidney function (RKF) has been associated with better survival, less morbidity, and improved quality of life in peritoneal dialysis (PD) patients. Since higher peritoneal clearance does not lead to better outcomes, more emphasis should be put on preserving kidney function. Many other benefits have been reported, including better volume and blood pressure control, better nutritional status, lower rates of PD peritonitis, preserved erythropoietin and vitamin D production, middle molecule clearance, lower Left Ventricular Hypertrophy, and better serum phosphate level. The most practical method of assessing RKF is the mean of 24-h urinary urea and creatinine clearance. Incremental PD prescription is an ideal option to supplement RKF in PD patients, which also offers more flexibility to the patient and, possibly, improved adherence. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be used when possible in PD patients to preserve RKF. Loop diuretics are underutilized in PD patients despite providing an additional means of maintaining fluid balance and reducing the need for higher glucose-containing PD solutions. In this paper, we outline the importance of RKF in PD patients and the different strategies for its preservation.

Residual kidney function for patients with chronic kidney disease (CKD) is associated with better quality of life and outcome; thus, strategies should be implemented to preserve kidney function. Among the multiple causes that promote kidney damage, gut dysbiosis due to increased uremic toxin production and endotoxemia need attention. Several strategies have been proposed to modulate the gut microbiota in these patients, and diet has gained increasing attention in recent years since it is the primary driver of gut dysbiosis. In addition, medications and faecal transplantation may be valid strategies. Modifying gut microbiota composition may mitigate chronic kidney damage and preserve residual kidney function. Although various studies have shown the influential role of diet in modulating gut microbiota composition, the effects of this modulation on residual kidney function remain limited. This review discusses the role of gut microbiota metabolism on residual kidney function and vice versa and how we could preserve the residual kidney function by modulating the gut microbiota balance.

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.