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Background: Lack of evaluations of the dietary phosphorus and dialysis phosphorus removal in daily clinical practice are common obstacles to assessing phosphorus balance and controlling phosphorus in hemodialysis patients. We aimed to investigate whether individualized therapy using a phosphorus balance calculator improves phosphorus control., Methods: A randomized, open-label, multicenter, 4-week clinical trial was conducted. A total of 119 maintenance hemodialysis patients aged 18-85 years old and with serum phosphorus level >1.45 mmol/L from three university teaching hospitals in Shanghai were enrolled. Patients were randomized in a 1:1 ratio to individualized therapy (n = 60) or conventional therapy (n = 59). The primary outcome was the serum phosphorus concentration after 4-week treatment. Secondary outcomes included the serum calcium and parathyroid hormone (PTH) concentrations, changes in serum phosphorus, calcium and PTH concentrations, and the proportion of patients achieving target ranges of serum phosphorus, calcium and PTH after 4-week treatment., Results: Among 119 randomized participants [mean age 62 years; 68 male (57%)], 116 completed the trial. Using the phosphorus balance calculator, the individualized group achieved a better phosphorus balance state and significantly reduced serum phosphorus (1.62 ± 0.45 mmol/L versus 1.85 ± 0.45 mmol/L, P = .006), increased the proportions of patients achieving target serum phosphorus range (41% versus 18%, P = .006) and had greater adjusted mean difference in change in serum phosphorus over the 4 weeks (-0.47 versus -0.23 mmol/L, P = .010) when compared with conventional therapy. No significant changes were observed in serum calcium and PTH levels, the proportion of patients achieving target serum calcium or PTH levels, or the adjusted mean difference of serum calcium and PTH levels over the treatment period., Conclusion: Phosphorus balance calculator was proved to improve serum phosphorus control in patients undergoing maintenance hemodialysis, offering a new tool for managing hyperphosphatemia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: There is a high prevalence of sarcopenia in maintenance hemodialysis (MHD) patients, which is known to be associated with increased mortality. This study is aimed at analyzing the risk factors affecting muscle mass decline in MHD patients., Methods: This retrospective study included MHD patients who underwent two body composition assessments in October 2013 and November 2017. Depending on whether there was muscle loss or not, the patients were divided into a normal muscle mass (NMM) group and a muscle mass decline (MMD) group. According to the muscle mass decline rate, patients in the MMD group were further classified into a low-rate group and a high-rate group. Biochemical variables, serum vitamin concentrations, anthropometric data, SGA, muscle mass, handgrip, and daily steps were assessed. Risk factors for muscle mass decline were screened by multivariate logistic analysis and linear regression analysis., Results: Of the 72 MHD patients included in this study, 33 were male and 39 were female with a mean age of 56.80 ± 10.86 years and a mean dialysis duration of 7.50 ± 5.20 years. Age ( P = .014) and serum 25(OH)D ( P = .040) were found to be associated with a higher risk of muscle mass decline after adjusting for gender, dialysis vintage, albumin, and hs-CRP ( P = .040). Further analysis found that dialysis vintage ( β = 0.285, P = .030), 25(OH)D ( β = -0.351, P = .007), and log NT-proBNP ( β = 0.312, P = .020) were risk factors associated with the muscle mass decline rate in MHD patients., Conclusion: Age and serum 25(OH)D were associated with a higher risk of muscle mass decline, while 25(OH)D, dialysis vintage, and NT-proBNP were associated with the muscle mass decline rate in MHD patients., Competing Interests: None of the authors reported relevant conflicts of interest., (Copyright © 2022 Yiqi Song et al.)

Background: Estimation of phosphate load in hemodialysis patients is always controversial in clinical practice. The aim of this study was to verify individual achievement rate of serum phosphate as the evaluation of phosphate load through investigating its impact on cardiovascular mortality in hemodialysis patients., Methods: This was a single-center, retrospective cohort study. A total of 251 maintenance hemodialysis patients were enrolled. The individual achievement rate of serum phosphate was defined as the times of tests within the target range divided by total times of tests over a period of time. Cox regression model was used to examine the relationship between individual achievement rate of serum phosphate and cardiovascular mortality., Results: The mean age of the study population was 61 ± 13 years old. A total of 44 (17.5%) patients died from cardiovascular disease (CVD) during a median follow-up of 65 months. Multivariable Cox analysis showed that one-year serum phosphate achievement rate of 0% (HR = 4.117, P = 0.016) and 25% (HR = 3.343, P = 0.023) increased the risk of cardiovascular mortality while the achievement rate of 50% (HR = 2.129, P = 0.162) and 75% (HR = 1.080, P = 0.902) did not, compared to the rate of 100%. Urea reduction ratio (URR) was positively, while serum intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), normalized protein catabolic rate (nPCR), and total phosphate-binding capacity of drug were negatively associated with achievement in target of serum phosphate., Conclusions: Keeping one-year achievement rate of serum phosphate higher than 50% provides significant clinical benefits in reducing cardiovascular mortality., (© 2021. The Author(s).)

Background: Our research group has previously reported a noninvasive model that estimates phosphate removal within a 4-h hemodialysis (HD) treatment. The aim of this study was to modify the original model and validate the accuracy of the new model of phosphate removal for HD and hemodiafiltration (HDF) treatment., Methods: A total of 109 HD patients from 3 HD centers were enrolled. The actual phosphate removal amount was calculated using the area under the dialysate phosphate concentration time curve. Model modification was executed using second-order multivariable polynomial regression analysis to obtain a new parameter for dialyzer phosphate clearance. Bias, precision, and accuracy were measured in the internal and external validation to determine the performance of the modified model., Results: Mean age of the enrolled patients was 63 ± 12 years, and 67 (61.5%) were male. Phosphate removal was 19.06 ± 8.12 mmol and 17.38 ± 6.75 mmol in 4-h HD and HDF treatments, respectively, with no significant difference. The modified phosphate removal model was expressed as Tpo4 = 80.3 × C45 - 0.024 × age + 0.07 × weight + β × clearance - 8.14 (β = 6.231 × 10-3 × clearance - 1.886 × 10-5 × clearance2 - 0.467), where C45 was the phosphate concentration in the spent dialysate measured at the 45th minute of HD and clearance was the phosphate clearance of the dialyzer. Internal validation indicated that the new model was superior to the original model with a significantly smaller bias and higher accuracy. External validation showed that R2, bias, and accuracy were not significantly different than those of internal validation., Conclusions: A new model was generated to quantify phosphate removal by 4-h HD and HDF with a dialyzer surface area of 1.3-1.8 m2. This modified model would contribute to the evaluation of phosphate balance and individualized therapy of hyperphosphatemia., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Purpose: Protein-energy wasting, characterized by decreased muscle mass, is one of the strongest predictors of mortality in patients on maintenance hemodialysis (MHD). As people get older, their muscle strength usually declines faster than muscle mass. However, the association between lower-limb muscle strength and all-cause mortality remains unclear. We aimed to evaluate risk factors for decreased upper-limb muscle strength in MHD patients and its impact on patient survival., Methods: The cross-sectional part of the study included 174 MHD patients. Subsequently, they were followed up for 52 weeks. Biceps muscle strength, anthropometry, body composition, dietary intake, daily steps, and biochemical indicators of malnutrition and inflammation were evaluated. Risk factors for muscle weakness were screened by multiple linear regression analysis, and patient survival was analyzed by Kaplan-Merier and Cox multivariate analysis., Results: The 174 MHD patients (93 men; 63.05 ± 12.29 years) were classified as a young (< 65 years, n = 97) group and an elderly group (≥ 65 years, n = 77). Gender, daily steps, muscle mass, 25(OH)D level and IL-6 in young group, and muscle mass, 25(OH)D, daily steps, and NT-proBNP in elderly group were associated with the decreased biceps muscle strength. The survival rate in high muscle strength group was significantly higher than that in low muscle strength group (P = 0.002). The association between low muscle strength and high mortality risk remained strong in the fully adjusted model., Conclusion: Risk factors of muscle weakness were different between young and elderly MHD patients. There was a strong correlation between strong biceps muscle strength and high patient survival.

Background: Both dialysis dose and residual kidney function (RKF) contribute to solute clearance and are associated with outcomes in hemodialysis patients. We hypothesized that the association between dialysis dose and mortality is attenuated with greater RKF., Methods: Among 32 251 incident hemodialysis patients in a large US dialysis organization (2007-11), we examined the interaction between single-pool Kt/V (spKt/V) and renal urea clearance (rCLurea) levels in survival analyses using multivariable Cox proportional hazards regression model., Results: The median rCLurea and mean baseline spKt/V were 3.06 [interquartile range (IQR) 1.74-4.85] mL/min/1.73 m2 and 1.32 ± 0.28, respectively. A total of 7444 (23%) patients died during the median follow-up of 1.2 years (IQR 0.5-2.2 years) with an incidence of 15.4 deaths per 100 patient-years. The Cox model with adjustment for case-mix and laboratory variables showed that rCLurea modified the association between spKt/V and mortality (Pinteraction = 0.03); lower spKt/V was associated with higher mortality among patients with low rCLurea (i.e. <3  mL/min/1.73 m2) but not among those with higher rCLurea. The adjusted mortality hazard ratios (aHRs) and 95% confidence intervals of the low (<1.2) versus high (≥1.2) spKt/V were 1.40 (1.12-1.74), 1.21 (1.10-1.33), 1.06 (0.98-1.14), and 1.00 (0.93-1.08) for patients with rCLurea of 0.0, 1.0, 3.0 and 6.0 mL/min/1.73 m2, respectively., Conclusions: Incident hemodialysis patients with substantial RKF do not exhibit the expected better survival at higher hemodialysis doses. RKF levels should be taken into account when deciding on the dose of dialysis treatment among incident hemodialysis patients.

Background and Objectives: The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality., Design, Setting, Participants, & Measurements: The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m 2 ) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011., Results: A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance ( P interaction =0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance ( i.e. , <1.5 ml/min per 1.73 m 2 ), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance ( i.e. , ≥1.5 ml/min per 1.73 m 2 ; P interaction <0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk ( P trend <0.001 for both) irrespective of residual renal urea clearance strata ( P interaction =0.34 and P interaction =0.53, respectively)., Conclusions: Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population., (Copyright © 2017 by the American Society of Nephrology.)

In the management of patients with chronic kidney diseases (CKD), a low-protein diet usually refers to a diet with protein intake of 0.6 to 0.8 grams per kilogram of body weight per day (g/kg/day) and should include at least 50% high-biologic-value protein. It may be supplemented with essential acids or nitrogen-free ketoanalogues if <0.6 g/kg/d. Low-protein diet can reduce proteinuria especially in non-diabetic CKD patients. In hypoalbuminemic patients it may lead to an increase in serum albumin level. By lowering proteinuria, decreasing nitrogen waste products, ameliorating metabolic burden, mitigating oxidative stress and acidosis, and lowering phosphorus burden, a low-protein diet can help delay dialysis start in advanced CKD. Low-protein diet is safe, since most CKD patients can maintain nitrogen balance by mechanisms of decreasing amino acid oxidation and protein degradation in addition to increased utilization of amino acids for protein synthesis. We suggest a dietary protein intake below 1.0 g/kg/day when estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2 or when there is solitary kidney or proteinuria at any level of GFR. Protein intake should be reduced progressively based on severity and progression of CKD and patient's nutritional status with a target of 0.6-0.8 g/kg/d in most patients with eGFR <45 mL/min/1.73 m2. The risk of protein-energy wasting can be overcome by careful attention to quantity and quality of the ingested proteins, sufficient energy intake of 30-35 Kcal/kg/d, and use of dietary supplements. Long-term observations and individualized approaches are needed to further demonstrate the benefits and safety of low-protein diet.

Coronary artery calcification (CAC) is associated with increased mortality in patients on maintenance hemodialysis (MHD), but the pathogenesis of this condition is not well understood. We evaluated the relationship of CAC score (CACs) and variability in serum phosphorus in MHD patients. Seventy-seven adults on MHD at Huashan Hospital (Shanghai) were enrolled in July, 2010. CAC of all the patients were measured by computed tomography and CACs was calculated by the Agatston method at the entry of enrollment. Patients were divided into three categories according to their CACs (0∼10, 11∼400, and >400). Blood chemistry was recorded every 3 months from January 2008 to July 2010. Phosphorus variation was defined by the standard deviation (SD) or coefficient of variation (CV) and it was calculated from the past records. The ordinal multivariate logistic regression analysis was used to analyze the predictors of CAC. The mean patient age (± SD) was 61.7 years (±11.3) and 51% of patients were men. The mean CACs was 609.6 (±1062.9), the median CACs was 168.5, and 78% of patients had CACs more than 0. Multivariate analysis indicated that female gender (OR = 0.20, 95% CI = 0.07-0.55), age (OR = 2.31, 95% CI = 1.32-4.04), serum fibroblast growth factor 23 (OR = 2.25, 95% CI = 1.31-3.85), SD-phosphorus calculated from the most recent 6 measurements (OR = 2.12; 95% CI = 1.23-3.63), and CV-phosphorus calculated from the most recent 6 measurements (OR = 1.90, 95% CI = 1.16-3.11) were significantly and independently associated with CACs. These associations persisted for phosphorus variation calculated from past 7, 8, 9, 10, and 11 follow-up values. Variability of serum phosphorus may contribute significantly to CAC and keeping serum phosphorus stable may decrease coronary calcification and associated morbidity and mortality in MHD patients.

Background: Residual kidney function (RKF) has consistently been a predictor of greater survival in maintenance hemodialysis (MHD) patients. The relationship between hemodialysis (HD) treatment frequency and RKF preservation has not been well examined. We hypothesized that initial twice-weekly HD helps in maintaining a longer RKF., Methods: In a dialysis center in Shanghai, 168 ESRD patients were screened and finally 85 patients were identified for this main cohort study. We first examined these 85 MHD patients; 30 of them were initiated with twice-weekly HD for 6 months or longer and 55 patients were started and maintained on thrice-weekly HD treatment. Then a subcohort study in 48 incident MHD patients was implemented to assess the independent risk factors responsible for RKF decline during the first year of HD therapy. Multivariate logistic regression analysis was then employed to examine the odds ratio of RKF loss., Results: The main cohort study showed that the clinical outcomes were almost the same between the two groups in 85 patients, but the percent of patients with RKF loss was significantly lower in the twice-weekly group compared with the thrice-weekly group, especially during the first year of HD initiation. In the 48 incident MHD patients, we found no significant differences between the two groups except for variations in the HD frequency, weekly Kt/V. The multivariate analysis showed that factors such as the male gender, HD frequency, URR and intradialytic hypotension episode were associated with RKF loss, and the odds ratio of RKF loss for each additional HD treatment per week was 7.2., Conclusion: Twice-weekly HD during the first year of dialysis therapy appears to be associated with better RKF preservation., (© 2014 S. Karger AG, Basel.)

Background and Objectives: High serum levels of fibroblast growth factor-23 (FGF-23) are associated with mortality in patients with ESRD, but whether it still acts as a phosphaturic factor is unknown. This study aimed to explore the role of circulating FGF-23 on urinary phosphate excretion and phosphate balance in maintenance hemodialysis (MHD) patients with residual renal function (RRF)., Design, Setting, Participants, & Measurements: There were 134 MHD patients enrolled in this cross-sectional study from June to July 2010. Demographics, laboratory data, and excretion capacity of phosphate were recorded. Multivariable linear regression was used to analyze the relationship of serum phosphate and the tubular reabsorption rate of phosphate with other factors., Results: The median age of the patients was 61.0 years and 47.8% were male. Thirty percent of the patients had high urinary output (>200 ml/d) accompanied by lower serum levels of phosphate, calcium, intact parathyroid hormone, and FGF-23 compared with those with low urine output (≤200 ml/d). The independent predictors of serum phosphate were normalized protein nitrogen appearance, intact parathyroid hormone, and FGF-23 in the low urine output group and female sex and GFR in the high urine output group. The tubular reabsorption rate of phosphate decreased to 50% of the normal level in patients with RRF. Elevated circulating FGF-23 was significantly associated with lower tubular phosphate reabsorption after adjusting for GFR., Conclusions: RRF is associated with significant capacity to excrete phosphate in MHD patients and high levels of serum FGF-23 may promote phosphate excretion by remnant nephrons.

Precise assessing phosphate removal by hemodialysis (HD) is important to improve phosphate control in patients on maintenance HD. We reported a simple noninvasive model to estimate phosphate removal within a 4-hour HD. One hundred sixty-five patients who underwent HD 4 hours per session using low-flux dialyzers made of polysulfone (1.2 m(2)) or triacetate (1.3 m(2)) were enrolled. Blood flows varied from 180 to 300 mL/min. Effluent dialysate samples were collected during the 4-hour HD treatment to measure the total phosphate removal. Predialysis levels of serum phosphate, potassium, hematocrit, intact parathyroid hormone, total carbon dioxide (TCO(2)), alkaline phosphatase, clinical and dialysis characteristics were obtained. One hundred thirty-five observations were randomly selected for model building and the remaining 30 for model validation. Total amount of phosphate removal within the 4-hour HD was mostly 15-30 mmol. A primary model (model 1) predicting total phosphate removal was Tpo(4)  = 79.6 × C(45) (mmol/L) - 0.023 × age (years) + 0.065 × weight (kg) - 0.12 × TCO(2) (mmol/L) + 0.05 × clearance (mL/min) - 3.44, where C(45) was phosphate concentration in spent dialysate measured at the 45 minute of HD and clearance was phosphate clearance of dialyzer in vitro conditions offered by manufacturer's data sheet. Since the parameter TCO(2) needed serum sample for measurement, we further derived a noninvasive model (model 2):Tpo(4)  = 80.3 × C(45)  - 0.024 × age + 0.07 × weight + 0.06 × clearance - 8.14. Coefficient of determination, root mean square error, and residual plots showed the appropriateness of two models. Model validation further suggested good and similar predictive ability of them. This study derived a noninvasive model to predict phosphate removal. It applies to patients treated by 4-hour HD under similar conditions., (© 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.)