Causal Effect of Chondroitin, Glucosamine, Vitamin, and Mineral Intake on Kidney Function: A Mendelian Randomization Study.

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, p-value = 2 × 10-4; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, p-value = 6 × 10-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.

Genetically Predicted Body Selenium Concentration and estimated GFR: A Mendelian Randomization Study.

Introduction: Selenium is a trace mineral that is commonly included in micronutrient supplements. The effect of selenium on kidney function remains unclear. A genetically predicted micronutrient and its association with estimated glomerular filtration rate (eGFR) can be used to assess the causal estimates by Mendelian randomization (MR). Methods: In this MR study, we instrumented 11 genetic variants associated with blood or total selenium levels from a previous genome-wide association study (GWAS). The association between genetically predicted selenium concentration and eGFR was first assessed by summary-level MR in the chronic kidney disease(CKDGen) GWAS meta-analysis summary statistics, including 567,460 European samples. Inverse-variance weighted and pleiotropy-robust MR analyses were performed, in addition to multivariable MR adjusted for the effects of type 2 diabetes mellitus. Replication analysis was performed with individual-level UK Biobank data, including 337,318 White individuals of British ancestry. Results: Summary-level MR analysis indicated that a genetically predicted 1 SD increase in selenium concentration was significantly associated with lower eGFR (-1.05 [-1.28, -0.82] %). The results were similarly reproduced by pleiotropy-robust MR analysis, including MR-Egger and weighted-median methods, and consistent even in the multivariable MR adjusted for diabetes. In the UK Biobank data, genetically predicted higher selenium concentration was also significantly associated with lower eGFR (- 0.36 [-0.52, -0.20] %), and the results were similar when body mass index, waist circumference, hypertension, and diabetes mellitus covariates were adjusted (-0.33 [-0.50, -0.17] %). Conclusion: This MR study supports the hypothesis that higher genetically predicted body selenium is causally associated with lower eGFR.

Effects of intravenous iron therapy on mortality and hospitalization of hemodialysis patients: A prospective cohort study in Korea.

Iron replacement therapy is necessary for anemia treatment in patients with advanced chronic kidney disease. Intravenous (IV) iron therapy is an efficient method for iron replacement. However, there are concerns regarding its considerable side effects, including increased risks of infection or major adverse cardiovascular events (MACE). This is a longitudinal study from a multicenter prospective cohort study conducted in the Korean end-stage renal disease population. All-cause mortality, death due to infection or MACE, hospitalization due to infection or MACE, and all adverse event of death or hospitalization due to infection or MACE were compared according to the iron replacement methods during the first 3 months of enrollment. Among 1,680 hemodialysis patients, 29.3% of patients received IV iron therapy, and 38% of patients received oral iron therapy. During the median 632 days follow-up, all-cause mortality, mortality or hospitalization due to infection or MACE, and all adverse events did not differ among iron replacement groups. There were significant differences related to the risk of all adverse events among iron replacement therapies in the log-rank test and univariate Cox regression analysis only in the prevalent dialysis patients; however, the significance was lost in multivariate Cox regression analysis. Similar results were observed in the 1-year short-term outcome analysis. High-dose IV iron did not increase adverse outcomes. All-cause mortality or all adverse events due to infection or MACE were not higher with the current clinical regimen of IV iron replacement therapy than with oral or no iron therapy in Korean hemodialysis patients.

Effect of sun exposure versus oral vitamin D supplementation on serum 25-hydroxyvitamin D concentrations in young adults: A randomized clinical trial.

BACKGROUND: Vitamin D inadequacy is associated with a wide range of diseases. However, optimal strategies to improve vitamin D status, especially in Asian populations, remain unclear. We tested the hypotheses that (1) relevant sun exposure or oral vitamin D supplementation would significantly increase serum 25-hydroxyvitamin D (25OHD) concentrations compared with placebo, (2) sun exposure and supplementary vitamin D would be similar in serum 25OHD increases, and (3) the two interventions may have different effects on cardio-metabolic markers. METHODS: In this 8-week randomized placebo-controlled clinical trial including vitamin D-deficient adults in Seoul (37 °N), Korea, changes in serum 25OHD concentrations were compared between the sun exposure (daily ≥20-30 min around noon, n = 50), oral vitamin D3 (500 IU/d, n = 50), and control (placebo, n = 50) groups. RESULTS: Both sun exposure and oral vitamin D3 effectively increased serum 25OHD concentrations. Compared with placebo, the between-group least-squares mean (LSM) differences in changes were 2.2 ng/mL (95% CI: 0.2, 4.2) in the sun exposure group and 8.5 ng/mL (6.5, 10.5) in the oral vitamin D3 group. Increases in serum 25OHD were greater with oral vitamin D3 than with sun exposure (LSM difference in changes = 6.3 ng/mL, 95% CI: 4.3, 8.3). More participants in the oral vitamin D3 group (54.2%) achieved serum 25OHD concentrations ≥20 ng/mL at week 8 than those in the sun exposure (12.2%) or control (4.3%) groups. Compliance with sun exposure advice was relatively low, and only those with adequate compliance had a significant increase in serum 25OHD. Changes in the cardio-metabolic markers were mostly insignificant in all groups. CONCLUSIONS: Enhanced sun exposure and 500 IU/d of oral vitamin D3 supplementation significantly increased serum 25OHD concentrations. However, our protocol for sun exposure was not as effective as 500 IU/d of oral vitamin D3 supplementation. This trial was registered at clinicaltrials.gov as NCT03310242.

Safety and efficacy of PG102P for the control of pruritus in patients undergoing hemodialysis (SNUG trial): study protocol for a randomized controlled trial.

BACKGROUND: Pruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory. PG102P, which is prepared from Actinidia arguta, has an immune-modulating effect on pruritus. This trial is designed to assess the antipruritic effect of PG102P compared with placebo. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial will include 80 patients undergoing hemodialysis. The patients will be randomized in a 1:1 ratio to a treatment group (PG102P 1.5 g/day) or a control group (placebo). The treatment will last for 8 weeks, followed by a 2-week observational period. During the observational period, all of the patients will maintain the antipruritic treatment previously used. The primary endpoint will be measured as the difference in visual analog scale between the groups before and after treatment. Secondary outcomes include serum levels of total immunoglobulin E, eosinophil cationic protein, potassium, calcium, phosphorus, intact parathyroid hormone, and blood eosinophil count between weeks 0 and 8. Kidney Disease and Quality of Life and Beck's Depression Inventory questionnaires will be conducted. Safety assessments and any adverse events that occur will also be evaluated. DISCUSSION: The SNUG is a clinical study that aims to investigate the antipruritic effect of PG102P to ameliorate itching in patients undergoing hemodialysis. TRIAL REGISTRATION: Clinical Trials.gov, NCT03576235. Registered on 4 July 2018.

Effectiveness of group cognitive behavioral therapy with mindfulness in end-stage renal disease hemodialysis patients.

BACKGROUND: Many patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) experience depression. Depression influences patient quality of life (QOL), dialysis compliance, and medical comorbidity. We developed and applied a group cognitive behavioral therapy (CBT) program including mindfulness meditation for ESRD patients undergoing HD, and measured changes in QOL, mood, anxiety, perceived stress, and biochemical markers. METHODS: We conducted group CBT over a 12-week period with seven ESRD patients undergoing HD and suffering from depression. QOL, mood, anxiety, and perceived stress were measured at baseline and at weeks 8 and 12 using the World Health Organization Quality of Life scale, abbreviated version (WHOQOL-BREF), the Beck Depression Inventory II (BDI-II), the Hamilton Rating Scale for Depression (HAM-D), the Beck Anxiety Inventory (BAI), and the Perceived Stress Scale (PSS). Biochemical markers were measured at baseline and after 12 weeks. The Temperament and Character Inventory was performed to assess patient characteristics before starting group CBT. RESULTS: The seven patients showed significant improvement in QOL, mood, anxiety, and perceived stress after 12 weeks of group CBT. WHOQOL-BREF and the self-rating scales, BDI-II and BAI, showed continuous improvement across the 12-week period. HAM-D scores showed significant improvement by week 8; PSS showed significant improvement after week 8. Serum creatinine levels also improved significantly following the 12 week period. CONCLUSION: In this pilot study, a CBT program which included mindfulness meditation enhanced overall mental health and biochemical marker levels in ESRD patients undergoing HD.

Early dialysis initiation does not improve clinical outcomes in elderly end-stage renal disease patients: A multicenter prospective cohort study.

BACKGROUND: The optimal timing for initiating dialysis in end-stage renal disease (ESRD) is controversial, especially in the elderly. METHODS: 665 patients ≥65 years old who began dialysis from August 2008 to February 2015 were prospectively enrolled in the Clinical Research Center for End-Stage Renal Disease cohort study. Participants were divided into 2 groups based on the median estimated glomerular filtration rate at the initiation of dialysis. Propensity score matching (PSM) was used to compare the overall survival rate, cardiovascular events, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) results, Karnofsky performance scale values, Beck's depression inventory values, and subjective global assessments. RESULTS: The mean patient age was 72.0 years, and 61.7% of the patients were male. Overall, the cumulative survival rates were lower in the early initiation group, although the difference was not significant after PSM. Additionally, the survival rates of the 2 groups did not differ after adjusting for age, sex, Charlson comorbidity index and hemoglobin, serum albumin, serum calcium and phosphorus levels. Although the early initiation group showed a lower physical component summary score on the KDQOL-36 3 months after dialysis, the difference in scores was not significant 12 months after dialysis. Furthermore, the difference was not significant after PSM. The Karnofsky performance scale, Beck's depression inventory, and subjective global assessments were not significantly different 3 and 12 months after dialysis initiation. CONCLUSIONS: The timing of dialysis initiation is not associated with clinical outcomes in elderly patients with ESRD.

Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia in kidney transplant recipients has been shown to predict poorer graft and patient survival. However, studies examining hypophosphatemia are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To evaluate the association of serum phosphorus level with patient and graft survival, we performed a retrospective multicenter cohort study. Between January of 1997 and August of 2012, 2786 kidney transplant recipients (41.7±11.4 years; 59.3% men; 73.5% living donors; 26.1% with diabetes; 3.8% with prior history of cardiovascular disease) were classified into seven groups according to serum phosphorus levels 1 year after transplantation, with intervals of 0.5 mg/dl (lowest group, <2.5 mg/dl; highest group, ≥5.0 mg/dl; reference group, 3.5-3.99 mg/dl). Survival analysis was performed by defining baseline time point as 1 year after transplantation. RESULTS: During median follow-up of 78.5 months, 60 patient deaths and 194 cases of graft loss occurred. In multivariate analysis, both lowest and highest serum phosphorus groups were associated with higher mortality, compared with the reference group (hazard ratio [HR], 4.82; 95% confidence interval [95% CI], 1.36 to 17.02; P=0.01; and HR, 4.24; 95% CI, 1.07 to 16.84; P=0.04, respectively). Higher death-censored graft loss was observed in the lowest and highest groups (HR, 3.32; 95% CI, 1.42 to 7.79; P=0.01; and HR, 2.93; 95% CI, 1.32 to 6.49; P=0.01, respectively), despite eGFR exhibiting no difference between the lowest group and reference group (65.4±19.3 versus 61.9±16.7 ml/min per 1.73 m2; P=0.33). Moreover, serum phosphorus showed a U-shape association with patient mortality and graft failure in restricted cubic spline curve analysis. CONCLUSIONS: Serum phosphorus level 1 year after transplantation exhibits a U-shape association with death-censored graft failure and patient mortality in kidney transplant patients characterized by relatively high rate of living donor transplant and low incidence of diabetes and prior cardiovascular disease compared with Western countries.

Lifestyle and Dietary Factors Associated with Serum 25-Hydroxyvitamin D Levels in Korean Young Adults.

Inadequate vitamin D status is highly prevalent in the Korean population, especially among young adults. Nonetheless, correlates of suboptimal vitamin D levels in young adults are not well defined. This study aimed to investigate potentially modifiable determinants of vitamin D levels in young adults in Korea. This cross-sectional study was based on health check-up data from 3,450 healthy male and female university students aged 18-29 yr in Seoul between April and May 2013. Serum 25-hydroxyvitamin D [25(OH)D] levels were determined using chemiluminescent immunoassay. Anthropometric data were measured, and lifestyle, dietary, and sociodemographic factors were obtained through self-administered questionnaires. General linear regression was used to assess correlates of serum 25(OH)D levels. The mean serum 25(OH)D level was 11.1 ng/mL, and the prevalence of 25(OH)D levels less than 10 ng/mL was 44.7% (39.5% in men, 50.2% in women). In a final multivariable model, significant positive correlates of serum 25(OH)D were older age, male sex, increased physical activity, sunlight exposure ≥ 30 min/day, eating breakfast regularly, consumption of dairy and fatty fish, and use of vitamin D-containing supplements. In contrast, significant inverse correlates were obesity (body mass index, BMI ≥ 25 kg/m(2)) or underweight (BMI < 18.5 kg/m(2)), abdominal obesity, increased sedentary time, and frequent consumption of instant noodles and sugar-sweetened beverages. In conclusion, many modifiable lifestyle and dietary factors were associated with low serum 25(OH)D levels in Korean young adults. Further studies on potential mechanisms of the correlates and optimal strategies to improve vitamin D status in this vulnerable subpopulation are warranted.

Obesity modifies the association between serum 25-hydroxyvitamin D and insulin resistance in Korean general population without increased fasting glucose levels.

The inverse relationship between 25-hydroxyvitamin D [25(OH)D] status and insulin resistance (IR) has been reported, but many interventional studies failed to reduce IR with 25(OH)D supplementation. In addition, there has been a paucity of literature on the interaction between 25(OH)D status and IR according to the degree of obesity in Asian subjects. We therefore evaluated the association between 25(OH)D status and IR according to the degree of obesity. Data from the Korea National Health and Nutrition Examination Survey in 2008-2010 were analyzed. The study subjects comprised 10,629 participants aged ≥20 years with fasting glucose<100 mg/dL. IR was estimated by the homeostasis model assessment (HOMA). We found an inverse linear association between 25(OH)D and loge(HOMA-IR) in multiple linear regression analysis; namely, 10 ng/mL increase of 25(OH)D was associated with 0.018 decrease of loge(HOMA-IR) (p<0.0001). In the subgroup analysis, we identified a distinct trend that the inverse linear association between 25(OH)D and loge(HOMA-IR) became more prominent with the progression of body mass index, waist circumference, or fat mass quartile (Q): -0.009, -0.004, -0.029 and -0.037 in Q1-Q4 of body mass index, -0.004, -0.014, -0.02 and -0.038 in Q1-Q4 of waist circumference, and -0.002, -0.001, -0.017 and -0.025 in Q1-Q4 of fat mass. Thus, the IR-lowering effect of 25(OH)D became more evident with the progression of obesity in an adult Korean population without increased fasting glucose levels. We suggest that proper supplementation of vitamin D might be beneficial in obese Korean adults.

Prevalence of vitamin D deficiency and effects of supplementation with cholecalciferol in patients with chronic kidney disease.

OBJECTIVE: We aimed to evaluate the vitamin D status, the effect of cholecalciferol supplementation, and the factors associated with vitamin D restoration in nondialytic patients with chronic kidney disease (CKD). DESIGN: The present study was a prospective open-label trial. SETTING: This study took place at the Seoul National University Boramae Medical Center. SUBJECTS: Patients with nondialytic CKD (estimated glomerular filtration rate [eGFR] 10-59 mL/min per 1.73 m(2)) participated in this study. INTERVENTION: Vitamin D status in 210 CKD patients was assessed and the patients with vitamin D deficiency (<30 ng/mL) were administered cholecalciferol (1,000 IU/day) for 6 months. MAIN OUTCOME MEASURE: The restoration rate of vitamin D deficiency at 3 and 6 months and the response-related factors were analyzed. RESULTS: The prevalence of vitamin D deficiency was 40.7% in CKD Stage 3, 61.5% in Stage 4, and 85.7% in Stage 5. The subgroup with vitamin D deficiency had a greater proportion of patients with diabetes, lower eGFR, and higher proteinuria. With the supplementation, 52 patients (76.5%) reached levels of 25-hydroxy vitamin D (25(OH)D) of 30 ng/mL or greater at 3 months, and the restoration of vitamin D was observed in 61 patients (89.7%) at 6 months. Lower levels of 25(OH)D and a higher amount of proteinuria at baseline were the factors associated with lower response to vitamin D supplementation. CONCLUSION: Vitamin D deficiency rate was high in nondialytic CKD patients, and the proportion increased as renal function decreased. A higher amount of proteinuria was the independent risk factor of nonresponse with supplementation. Vitamin D was replenished in most patients with cholecalciferol supplementation without any significant adverse effects.