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.

Hyperphosphatemia and risks of acute kidney injury, end-stage renal disease, and mortality in hospitalized patients.

BACKGROUND: Hyperphosphatemia is associated with vascular calcification and bone mineral disorders and is a major concern among patients with chronic kidney disease (CKD). However, the relationship between hyperphosphatemia and renal outcome in non-CKD patients has not been studied. Furthermore, the clinical implications of hyperphosphatemia in relation to the risks of acute kidney injury (AKI), end-stage renal disease (ESRD), and mortality after hospitalization remain unresolved. METHODS: A total of 20,686 patients (aged ≥18 years) admitted to Seoul National University Bundang Hospital from January 2013 to December 2013 were retrospectively reviewed. Patients were divided into quartiles according to serum phosphorus level at the time of admission. The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD and all-cause mortality were calculated after adjustment of multiple covariates. RESULTS: AKI developed in 2319 patients (11.2%), with higher ORs for patients in the third and fourth quartiles (1.4 [1.24-1.68] and 2.8 [2.44-3.22], respectively) compared with the first quartile group. During a median follow-up period of 4.0 years, 183 patients (0.88%) developed ESRD and 3675 patients (17.8%) died. Patients in the fourth quartile had higher risks of ESRD and mortality than patients in the first quartile (HRs, 2.3 [1.46-3.75] and 1.4 [1.22-1.49], respectively). These trends remained consistent in patients with an estimated glomerular filtration rate > 60 ml/min/1.73 m2. CONCLUSIONS: Hyperphosphatemia is related to the risks of AKI, ESRD, and mortality, and it may therefore be necessary to monitor serum phosphorus level in hospitalized patients, irrespective of kidney function.

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.