Oral vitamin D supplementation on the prevention of peritoneal dialysis-related peritonitis: A pilot randomised controlled trial.

OBJECTIVE: Peritoneal dialysis (PD)-related peritonitis is independently associated with low serum 25-hydroxy vitamin D [25(OH)D] levels. Our objective is to examine the feasibility of conducting a large, randomised controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis. DESIGN: Pilot, prospective, open-label randomised controlled trial. SETTING: Peking University First Hospital, China. PARTICIPANTS: Patients receiving PD who had recovered from a recent episode of peritonitis between 30 September 2017 and 28 May 2020. INTERVENTIONS: Oral natural vitamin D supplementation (2000 IU per day) versus no vitamin D supplementation for 12 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25(OH)D level during follow-up) for a large, randomised controlled trial in the future to determine the effects of vitamin D on PD-related peritonitis. Secondary outcomes were time to peritonitis occurrence and outcome of subsequent peritonitis. RESULTS: Overall, 60 among 151 patients were recruited (recruitment rate was 39.7%, 95% CI 31.9-47.5%, recruitment rate among eligible patients was 61.9%, 95% CI 52.2-71.5%). Retention and adherence rates were 100.0% (95% CI 100.0-100.0%) and 81.5% (95% CI 66.8-96.1%), respectively. During follow-up, serum 25(OH)D levels increased in the vitamin D (VD) group (from 19.25 ± 10.11 nmol/L to 60.27 ± 23.29 nmol/L after 6 months, p < 0.001, n = 31), and remained higher (p < 0.001) than those in the control group (n = 29). No differences were observed between the two groups with respect to time to subsequent peritonitis (hazard ratio 0.85, 95% CI 0.33-2.17) or any of the peritonitis outcomes. Adverse events were uncommon. CONCLUSIONS: A randomised controlled trial of the effect of vitamin D supplementation on peritonitis occurrence in patients receiving PD is feasible, safe and results in adequate serum 25(OH)D levels.

Associations between small and middle molecules clearance and the change of cognitive function in peritoneal dialysis.

BACKGROUND: Uremic toxins have been suspected as potential contributors for cognitive impairment in peritoneal dialysis (PD) patients. However, associations between the clearance of serum small and middle molecules and the change of cognitive function were not fully explored and then we explored this issue in the present study. METHOD: A total of clinically-stable 222 patients on PD were enrolled and then followed up for 2 years in this single-center prospective cohort study. Small and middle molecules clearances were examined by urea clearance (Kt/V), creatinine clearance (Ccr) and beta-2 microglobulin (B2M) clearance via dialysate and urine at baseline and after 2 years. Global and specific cognitive impairment were measured at baseline and after 2 years. Modified Mini-Mental State Examination (3MS) was assessed for global cognitive function, trail-making tests A and B for executive function and subtests of the battery for the assessment of neuropsychological status for immediate and delayed memory, visuospatial skills and language ability. RESULTS: The median of total Kt/V, Ccr and B2M clearance were 1.89, 53.2 l/w/1.73 m2 and 17.5 l/w/1.73 m2, respectively at baseline. The prevalence of global cognitive impairment was 12.3% for 222 patients and 15.4% for the remained 130 patients after 2 years. At baseline, total Kt/V was independently positively associated with delayed memory function. Total and dialysate beta-2 microglobulin clearance was positively associated with 3MS scores and negatively with completion time on trail A after multivariate adjustment. At 2 years, we observed a significant difference in the changing trend of 3MS scores between groups divided by total B2M clearance (P = 0.033), which still maintained to be meaningful after multivariate adjustment (P = 0.024). Patients with total B2M clearance > 19.0 l/w/1.73 m2 got significant improvement on their 3MS scores (P = 0.005). Patients divided by total Kt/V or Ccr were not significantly different in the trends of general and any specific cognitive function during the follow up. CONCLUSION: The higher middle molecules clearance independently correlated to better performance on general cognitive and executive function in PD patients, which also predict an improvement in general cognitive function during the follow up.

The effects of oral vitamin D supplementation on the prevention of peritoneal dialysis-related peritonitis: study protocol for a randomized controlled clinical trial.

BACKGROUND: Vitamin D deficiency has been shown to be closely associated with peritoneal dialysis (PD)-related peritonitis. The aim of this study is to examine the feasibility of conducting a large, powered randomized controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis in patients who have already experienced an episode of peritonitis. METHODS: This prospective, open-label randomized controlled pilot trial with blinded end-points aims to determine the feasibility of oral vitamin D supplementation and to explore its effects on the risk of subsequent PD-related peritonitis among PD patients who have recovered from a recent episode of peritonitis. Eligible patients will be randomized 1:1 to either oral vitamin D supplementation (2000 IU per day; intervention group) or no vitamin D supplementation (control group) in addition to usual care according to International Society for Peritoneal Dialysis guidelines. The sample size will be 30 patients for both groups. All participants will be followed for 12 months. The primary outcome is the assessment of feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25-hydroxyvitamin D level during follow-up) for a large, powered randomized controlled trial to determine the effects of vitamin D on the risk of PD-related peritonitis in the future. Secondary outcomes include time to peritonitis occurrence, recovery of peritonitis, peritonitis-related transition to hemodialysis, and peritonitis-related death (defined as death within 30 days of peritonitis onset). DISCUSSION: This is the first randomized controlled trail investigating the effects of vitamin D supplementation on the risk of subsequent PD-related peritonitis among patients on PD. The findings for this pilot study will determine the feasibility of conducting a full-scale randomized controlled trail, which may provide a new strategy for preventing PD-related peritonitis among PD patients. TRIAL REGISTRATION: Clinicaltrails.gov, NCT03264625. Registered on 29 August 2017.

Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. METHODS: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate). Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. RESULTS: Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64), 1.67 (1.09-2.57), and 2.49 (1.07-5.77), respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39). CONCLUSION: Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients.

Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

BACKGROUND: Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. STUDY DESIGN: Multicenter cross-sectional study. SETTING & PARTICIPANTS: 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. PREDICTOR: Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. OUTCOMES: Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. LIMITATIONS: The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. CONCLUSIONS: Even mild depression is closely associated with global and specific cognitive impairment in PD patients.

Vitamin D Status Is an Independent Risk Factor for Global Cognitive Impairment in Peritoneal Dialysis Patients.

OBJECTIVE: Vitamin D (VD) deficiency is an independent risk factor for cognitive impairment (CI) in the general population, but VD status in peritoneal dialysis (PD) patients has not been investigated. In this study, we aimed to investigate the relationship between serum VD levels and global and specific cognitive functions in PD patients. DESIGN AND SETTING: Cross-sectional study, simultaneously conducted at two PD centers. PATIENTS: Clinically stable patients (n = 273) undergoing PD for at least 3 months were enrolled over a period of one year. MAIN OUTCOME MEASURES: Demographic and comorbidity data were recorded, and routine biochemical parameters and serum 25-hydroxyvitamin D (25(OH) D) levels of overnight fasted patients were determined. Global cognitive function was assessed by the Modified Mini-Mental State Examination (3MS) score; executive function, by the trail making tests (Trails A and B); and immediate memory, delayed memory, and language ability by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) sub-tests. RESULTS: In the univariate analysis, serum 25(OH) D levels significantly correlated with 3MS scores (r = -0.139; P = 0.02), and Trail A (r = -0.188; P = 0.002) and B (r = -0.154; P = 0.01) completion times. In the multivariate analysis, 25(OH) D was found to be independently associated with global CI, but not with executive dysfunction. Serum 25(OH) D could not predict scores of immediate/delayed memory and language ability. CONCLUSIONS: VD deficiency is highly prevalent in PD patients and is an independent risk factor for global CI in this patient cohort.

Hyponatremia and Cognitive Impairment in Patients Treated with Peritoneal Dialysis.

BACKGROUND AND OBJECTIVES: Hyponatremia has been identified as a relevant factor for cognitive impairment but has not been investigated in patients receiving peritoneal dialysis (PD). This study investigated the relationship between hyponatremia and cognitive functions in PD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 476 clinically stable patients from five PD units who were older than 18 years of age and had undergone PD for at least 3 months between March 2013 and March 2014 were enrolled in this multicenter cross-sectional study. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS); executive function, by trail making tests A (trails A) and B (trails B); and immediate memory, delayed memory, and language ability, by subtests of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Hyponatremia was defined as serum sodium level ≤135 mmol/L, which was calculated as the mean of measurements taken over the preceding 3 months. RESULTS: Fifty patients (10.5%) had hyponatremia; these patients tended to be older and less educated, to have less inflammation, and to have the higher prevalence of cognitive impairment. They also had lower scores on RBANS subtests. After adjustment for demographic and clinical confounders, hyponatremia was independently associated with lower 3MS score (coefficient, -5.28; 95% confidence interval [CI], -8.44 to -2.13) and longer completion time of trials A (coefficient, 22.68; 95% CI, 3.44 to 41.92) and B (coefficient, 45.56; 95% CI, 1.30 to 89.81). After additional adjustment for laboratory measures, hyponatremia was still associated with 3MS score and completion time of trails A. Hyponatremia was independently associated with CI (odds ratio, 2.17; 95% CI, 1.02 to 4.94) and executive dysfunction (odds ratio, 2.43; 95% CI, 1.01 to 5.87) using multivariate logistic regression analysis. Sensitivity analyses with multivariable models that included propensity score still supported the association between hyponatremia and cognitive impairment. CONCLUSIONS: Hyponatremia was associated with global and specific cognitive impairment in PD patients.

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis.

UNLABELLED: ♦ BACKGROUND: As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ METHODS: We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ RESULTS: The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 - 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 - 0.75), respectively. ♦ CONCLUSIONS: Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis.