Therapeutic Effects of Add-On Tenapanor for Hemodialysis Patients with Refractory Hyperphosphatemia

<b><i>Introduction:</i></b> Phosphate binders are used to treat hyperphosphatemia. Some patients have inappropriately controlled serum phosphorus levels, which may occur for many reasons, including a high pill burden and adverse events (AEs). Tenapanor selectively inhibits the passive paracellular transfer of phosphate in the gastrointestinal tract, thereby reducing serum phosphorus levels. This novel mechanism of action may contribute to improved phosphate management. The efficacy and safety of tenapanor have not been evaluated in Japanese patients with high serum phosphorus levels despite treatment with phosphate binders. This study aimed to assess the efficacy and safety of add-on tenapanor therapy for reducing serum phosphorus levels in this population. <b><i>Methods:</i></b> This multicenter, double-blind, randomized, placebo-controlled trial enrolled patients with refractory hyperphosphatemia undergoing hemodialysis. Patients were randomly assigned in a 1:1 ratio to receive tenapanor or placebo as an add-on to their phosphate binder regimen for 6 weeks. Change in serum phosphorus levels at week 6 (day 43) compared with the baseline value (day 1, week 0) (primary endpoint), achievement of target serum phosphorus levels (serum phosphorus level ≤6.0 or ≤5.5 mg/dL), and safety, based on all AEs and drug-related AEs, were among the outcomes evaluated. <b><i>Results:</i></b> In total, 24 patients were randomly assigned to the placebo group and 23 to the tenapanor group. The mean serum phosphorus level decreased from 7.01 mg/dL on day 1 to 6.69 mg/dL on day 43 in the placebo group and from 6.77 mg/dL on day 1 to 4.67 mg/dL on day 43 in the tenapanor group. In the placebo and tenapanor groups (modified intent-to-treat population), the mean (standard deviation) change in the serum phosphorus level at day 43 (last observation carried forward [LOCF]) was 0.08 (1.52) mg/dL and −1.99 (1.24) mg/dL, respectively, with a between-group difference of −2.07 (95% confidence interval: −2.89, −1.26; <i>p</i> &#x3c; 0.001). The target achievement rate (serum phosphorus level ≤6.0 mg/dL at week 6 [LOCF]) was 37.5 and 87.0% in the placebo and tenapanor groups, respectively. Diarrhea was the most common drug-related AE, and it occurred in 8.3 and 65.2% of patients in the placebo and tenapanor groups, respectively. No specific AEs were observed with add-on tenapanor or with phosphate binders. <b><i>Discussion/Conclusion:</i></b> Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binders. No new safety signals were raised, and add-on tenapanor was generally well tolerated.

MO456DOES PHOSPHORUS EXCRETION PER NEPHRON AFFECT THE PROGNOSIS OF CHRONIC KIDNEY DISEASE?

Background and Aims Serum phosphorus is an important factor associated with mortality and cardiovascular disease in dialysis patients as well as in non-dialysis patients with chronic kidney disease (CKD) and healthy individuals. One observational study reported that elevated phosphorus is a risk factor for end-stage renal disease and is linked to reduced renal function, even within the normal range. Although the mechanism is unknown, an excessive load of phosphorus to the kidney is presumed to cause renal damage via phosphorus-containing nanoparticles. In this study, we examined the association between phosphorus excretion per nephron and the prognosis of CKD. Method A single-center, retrospective cohort study was conducted in 276 patients with CKD category G3 to G5 who were admitted to our hospital and received an inpatient educational program on CKD between June 2016 and November 2019 and who could be followed up for at least 1 year or started on dialysis within 1 year after hospitalization. Phosphorus excretion per nephron was defined as daily phosphorus excretion divided by creatinine clearance (Ccr), and its association with the annual rate of decline in estimated glomerular filtration rate (eGFR) was investigated for each CKD category. For statistical analysis, multiple regression analysis was performed using the following covariates: age, sex, presence/absence of diabetes mellitus, mean arterial blood pressure, amount of daily urine protein, serum phosphorus level, and use of a renin-angiotensin system inhibitor. Results There were 108 patients with CKD G3, 106 patients with CKD G4, and 62 patients with CKD G5. Daily phosphorus excretion was 442 mg in G3, 350 mg in G4, and 350 mg in G5 patients. Phosphorus excretion per nephron was 8.4 mg/Ccr in G3, 14.0 mg/Ccr in G4, and 24.2 mg/Ccr in G5 patients. It increased with the progression of renal damage. In G4 patients, phosphorus excretion per nephron was significantly negatively correlated with the rate of decline in eGFR (p = 0.004); however, no correlation was found between the two in G3 and G5 patients (p = 0.09 and p = 0.16, respectively). Multiple regression analysis showed that phosphorus excretion per nephron was not a significant worsening factor for renal function in G3, G4, and G5 patients (p = 0.09, p = 0.36, and p = 0.41, respectively). On the other hand, serum phosphorus level was a significant worsening factor for renal function in G3 and G5 patients (p = 0.03 and p = 0.01, respectively). Conclusion No association was found between phosphorus excretion per nephron and the rate of the subsequent decline in renal function.

Predictive Factors for In-Hospital Preoperative Rupture in Hyperacute Type A Aortic Dissection

Objective: This study aims to figure out risk factors of in-hospital preoperative rupture of hyperacute type A aortic dissection (haTAAD) patients and build a prediction and risk stratification model. Methods: From January 2011 to December 2019, 830 patients diagnosed as haTAAD from Nanjing Drum Tower Hospital were enrolled. Among them, 799 patients received prompt surgery and 31 suffered aortic rupture before operation. The association between in-hospital preoperative rupture and perioperative parameters were examined. Best subset selection was used for feature selection and ROC curve was used to identify the model. Results: Age, winter season, back pain, preoperative hypotension, albumin and globulin ratio, high serum phosphorus level are risk factors for in-hospital preoperative rupture of haTAAD. On the basis of six variables with AUC 0.828, a nomogram was established. According to the robustness test, actual in-hospital preoperative ruptures were fitted well. Conclusions: The in-hospital rupture prediction model was developed using logistic regression analysis. High serum phosphorus level is one of the strongest predictors. This nomogram may be useful when evaluating the risk of aortic dissection in-hospital rupture in future trials.

Body mass index and blood urea nitrogen to creatinine ratio predicts refeeding hypophosphatemia of anorexia nervosa patients with severe malnutrition

Aim To investigate development of refeeding hypophosphatemia during the refeeding period and the extent of the decrease in the serum phosphorus level among anorexia nervosa patients with severe malnutrition. Objective The accurate prediction of the severity of refeeding hypophosphatemia in patients with anorexia nervosa during acute treatment is of great importance. Although some predictors were found in previous reports, these studies used binominal data—the presence or absence of hypophosphatemia—as an outcome indicator but not the extent of serum phosphorus level decrease. It is crucial in clinical settings to predict the extent of the serum phosphorus level decrease as well as development of refeeding hypophosphatemia, in particular, for patients with severe malnutrition, who has a higher risk of death. Methods We investigated 63 admissions from 37 patients with anorexia nervosa who had severe malnutrition (admission body mass index 11.5 ± 1.6) and carried out a linear discriminant regression analysis for the development of refeeding hypophosphatemia. The extent of the decrease in the serum phosphorus level were investigated using multiple linear regression analysis. Explanatory variables included data upon admission (age, sex, body mass index, blood urea nitrogen to creatinine ratio, albumin, initial serum phosphorus level, anorexia nervosa type, i.e., restrictive or binge-purge) as well as treatment-related indicators (calorie intake, amount of phosphate administered, and rate of weight gain). Results Development of refeeding hypophosphatemia and a change in serum phosphorus levels were predicted by body mass index and elevated blood urea nitrogen to creatinine ratio. Conclusions Our study found that refeeding hypophosphatemia among patients with severe malnutrition was predicted by a lower body mass index and elevated blood urea nitrogen to creatinine ratio.

Abstract 13331: Impact of Longer Hemodialysis Vintage With Higher Serum Phosphorus Level on Clinical Outcomes in Patients With Chronic Limb-threatening Ischemia

Background: Although hemodialysis vintage and serum phosphorus level adversely impact on outcomes in the field of general population on hemodialysis, it has not systematically studied whether these have similar prognostic impacts on clinical outcomes in population with chronic limb-threatening ischemia (CLTI). Methods: The current study retrospectively analyzed 374 hemodialysis patients with CLTI presenting ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 39.6%, Rutherford 5: 75.9%, 6: 24.1%, WIFI stage 4: 50.0%) primarily treated with endovascular therapy (EVT) between April 2007 and December 2016. Primary outcome measure was 1-year amputation-free survival (AFS), while secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. Result: One-year rate of AFS and wound healing rate were 70.5±2.5%, and 57.1±3.0%, respectively. Multivariate analysis demonstrated that body mass index (hazard ratio [HR], 0.918; 95% confidence interval [CI], 0.859-0.981; p=0.012), non-ambulatory status (HR, 1.887; 95% CI, 1.222-2.913; p=0.004), lower serum albumin level (HR, 0.591; 95% CI, 0.414-0.844; p=0.004), WIfI stage 4 (HR, 1.782; 95% CI, 1.156-2.748; p=0.009) and longer vintages for hemodialysis with higher serum phosphorus levels (HR, 1.670; 95% CI, 1.099-2.537; p=0.016) were significantly associated with 1-year AFS (Figure), while WIfI stage 4 (HR, 0.713; 95% CI, 0.519-0.979; p=0.037) was associated and longer vintages for hemodialysis with higher serum phosphorus levels was close to significant association (HR, 0.684; 95% CI, 0.467-1.000; p=0.050) with 1-year wound healing. Conclusion: Longer hemodialysis vintage with higher serum phosphorus level would adversely affect clinical outcomes after EVT for hemodialysis patients with CLTI presenting ischemic tissue loss.

Effect of Neighborhood Food Environment and Socioeconomic Status on Serum Phosphorus Level for Patients on Chronic Dialysis

BackgroundElevated blood phosphorus levels are common and associated with a greater risk of death for patients receiving chronic dialysis. Phosphorus-rich foods are prevalent in the American diet, and low-phosphorus foods, including fruits and vegetables, are often less available in areas with more poverty. The relative contributions of neighborhood food availability and socioeconomic status to phosphorus control in patients receiving dialysis are unknown.MethodsUsing longitudinal data from a national dialysis provider, we constructed hierarchical, linear mixed-effects models to evaluate the relationships between neighborhood food environment or socioeconomic status and serum phosphorus level among patients receiving incident dialysis.ResultsOur cohort included 258,510 patients receiving chronic hemodialysis in 2005–2013. Median age at dialysis initiation was 64 years, 45% were female, 32% were Black, and 15% were Hispanic. Within their residential zip code, patients had a median of 25 “less-healthy” food outlets (interquartile range, 11–40) available to them compared with a median of four “healthy” food outlets (interquartile range, 2–6). Living in a neighborhood with better availability of healthy food was not associated with a lower phosphorus level. Neighborhood income also was not associated with differences in phosphorus. Patient age, race, cause of ESKD, and mean monthly dialysis duration were most closely associated with phosphorus level.ConclusionsNeither neighborhood availability of healthy food options nor neighborhood income was associated with phosphorus levels in patients receiving chronic dialysis. Modifying factors, such as nutrition literacy, individual-level financial resources, and adherence to diet restrictions and medications, may be more powerful contributors than food environment to elevated phosphorus.

Comparison of the Effect of Enteral Feeding through the Bolus and Continuous Methods on Serum Phosphorus and Glucose Levels in Patients with Mechanical Ventilation: A Randomized Clinical Trial

Introduction. Patients who are under mechanical ventilation in intensive care units need to have nutritional support. Also, feeding methods affect serum phosphorus and glucose levels, which are very important in weaning patients off the ventilator. Thus, this study is to compare the effects of both bolus and continuous enteral feeding methods on serum phosphorus and glucose levels in patients with mechanical ventilation. Methods. In this clinical trial study, 34 patients in the intensive care unit of Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences satisfied inclusion criteria and were randomly divided into control and intervention groups. Sampling was done between October and February 2018. The intervention group received continuous enteral feeding for one week, and the control group received nutrition by the bolus method. The blood glucose level was measured every six hours, and the serum phosphorus level was recorded at the beginning and the end of the intervention, based on the data entry form with respect to all ethical considerations. Data analysis was done by SPSS-20 software. Results. The serum phosphorus level was significantly increased in the intervention group (P=0.004) and in the control group (P<0.001) and was compared with the previous intervention. No significant difference was found between the intervention and control groups before and after the intervention (P=0.22) and also one week after the intervention (P=0.14). There was also no significant difference between the glucose levels from day 1 to day 7 in the control group (P=0.33) and the intervention group (P=0.086). Discussion. Nutritional support in both bolus and continuous methods increased the serum phosphorus level. It indicates the importance of the nutritional method in controlling the phosphorus level in critically ill patients. However, there was no difference between the effects of dietary methods on blood glucose control.

Clinical Observation and Analysis of Patients with Idiopathic Membranous Nephropathy Combined with Low 25(OH) D3 Levels

Background: To investigate the correlations between 25-hydroxyvitamin D3 [25(OH) D3] levels and selected clinical indicators and renal pathology at initial onset of idiopathic membranous nephropathy (IMN) and to analyze changes in the main quantifiable indicators in IMN patients with different 25(OH) D3 levels.Methods: A total of 109 patients admitted to the Department of Nephrology of the First Affiliated Hospital of Guangxi Medical University between August 2015 and April 2019 and diagnosed with IMN were reviewed. Comparative analysis of the effects of different 25(OH)D3 levels on clinical and pathological indicators of IMN was performed, and the changes in serum albumin, eGFR, serum creatinine and other clinical indicators in these patients during follow-up were analyzed.Results: The 109 patients with IMN had 25(OH)D3 deficiency [25(OH)D3<70 nmol/L]. The incidence of nephrotic syndrome, serum phosphorus level, hs-CRP level, and ESR were higher in the 25(OH)D3<25nmol/L group than in the 25(OH)D3≥25nmol/L group. In contrast, the TP, ALB, serum calcium, and IgG levels were lower in the 25(OH)D3<25nmol/L group (P<0.05). No pathological parameters differed significantly between the two groups (P>0.05). Bivariate correlation analysis showed that 25(OH)D3 was positively correlated with nephrotic syndrome, the TP level, the ALB level, the eGFR, the serum calcium level and the IgG level (P<0.05) and negatively correlated with age, blood pressure, the Scr level, 24-hour UP quantitation, the serum phosphorus level, the hs-CRP level and the ESR (P<0.05). In single-factor repeated measures analysis of variance, the ALB levels in the 25(OH)D3<25nmol/L and 25(OH)D3≥25nmol/L groups showed an increasing trend but were lower in the 25(OH)D3<25nmol/L group than in the 25(OH)D3≥25 nmol/L group at each follow-up time point (P<0.001).Conclusion: Reduced 25(OH)D3 levels are prevalent among IMN patients. During follow-up, serum albumin increased significantly in patients administered vitamin D supplementation. 25(OH)D3 may play an important role in IMN development.

Strong Correlation of Renal Function with Choroidal Thickness in Patients with Type 2 Diabetes: Retrospective Cross-Sectional Study

The purpose of this study was to analyze the correlation between renal function and subfoveal choroidal thickness (SFChT) in treatment-naïve proliferative diabetic retinopathy (PDR) patients. This study included 85 eyes of 52 treatment-naïve PDR patients who underwent kidney function testing and urinalysis and 42 eyes of 33 age-matched controls. Treatment-naïve eyes with PDR were categorized into pachychoroid and leptochoroid groups based on the SFChT of the control group. Kidney function profiles were compared between pachychoroid and leptochoroid groups; the relationship between kidney function profile and SFChT was evaluated using regression analysis. Compared with the pachychoroid group, the leptochoroid group had significantly higher serum creatinine (p = 0.026), cystatin C (p = 0.004), and phosphorus (p < 0.001) levels and a lower estimated glomerular filtration rate (eGFR) (p < 0.001). Multivariate linear regression analyses showed that SFChT was positively correlated with eGFR (Cystatin C) (p = 0.007) and negatively correlated with serum phosphorus (p = 0.001). SFChT of patients with eGFR < 30 mL/min/1.73 m2 and serum phosphorus level ≥4.0 mg/dL was less than that of patients with higher eGFR and lower serum phosphorus level. The choroidal thickness of treatment-naïve PDR patients is closely affected by renal function. Kidney function test should be considered if SFChT of patients with treatment-naïve PDR is reduced.