Decisive evidence corroborates a null relationship between MTHFR C677T and chronic kidney disease: A case-control study and a meta-analysis.

BACKGROUND: Previous meta-analyses have explored the association between the C677T polymorphism of methyltetrahydrofolate reductase (MTHFR) and chronic kidney disease (CKD) but there were no studies with a decisive conclusion. Furthermore, the high heterogeneity among different populations is not yet interpreted. OBJECTIVES: This study used trial sequential analysis (TSA) to evaluate whether the nowadays conclusion supported by current cumulative samples. We also applied case-weighted meta-regression to explore the potential gene-environment interactions. METHODS: For the first stage of this study we conducted a case-control study involving 847 dialysis patients from 7 hemodialysis centers in Taipei during 2015 to 2018 and 755 normal controls from a health center in the Tri-Service General Hospital. The second stage combined the results from the first stage with previous studies. The previous studies were collected from PubMed, EMBASE, and Web of Science databases before January 2018. RESULTS: From the case-control study, the T allele of MTHFR C677T appeared to have a protective effect on end-stage renal disease compared with the C allele [odds ratio (OR): 0.80, 95% CI (confidence interval) = 0.69-0.93]. However, the meta-analysis contradicted the results in Asian (OR = 1.12, 95% CI = 0.96-1.30). The same analysis was also applied in Caucasian and presented similar results from Asian (OR = 1.18, 95% CI = 0.98-1.42). The TSA showed our case-control study to be the decisive sample leading to a null association among Asian population. The high heterogeneity (I = 75%) could explain the contradictory results between the case-control study and the meta-analysis. However, further case-weighted meta-regression did not find any significant interaction between measured factors and MTHFR C677T on CKD. CONCLUSIONS: High heterogeneities were found in both Caucasian and Asian, which caused the null relationship in meta-analysis while there were significant effects in individual studies. Future studies should further explore the high heterogeneity that might be hidden in unmeasured gene-environment interactions, to explain the diverse findings among different populations.

Investigation of the variants at the binding site of inflammatory transcription factor NF-κB in patients with end-stage renal disease.

BACKGROUND: A chronic inflammatory state is a prominent feature in patients with end-stage renal disease (ESRD). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates the expression of genes involved in inflammation. Some genetic studies have demonstrated that the NF-κB genetic mutation could cause kidney injury and kidney disease progression. However, the association of a gene polymorphism in the transcription factor binding site of NF-κB with kidney disease is not clear. METHODS: We used the Taiwan Biobank database, the University of California, Santa Cruz, reference genome, and a chromatin immunoprecipitation sequencing database to find single nucleotide polymorphisms (SNPs) at potential binding sites of NF-κB. In addition, we performed a case-control study and genotyped 847 patients with ESRD and 846 healthy controls at Tri-Service General Hospital from 2015 to 2016. Furthermore, we used the ChIP assay to identify the binding activity of different genotypes and used Luciferase reporter assay to examine the function of the rs9395890 polymorphism. RESULT: The results of biometric screening in the databases revealed 15 SNPs with the potential binding site of NF-κB. Genotype distributions of rs9395890 were significantly different in ESRD cases and healthy controls (P = 0.049). The ChIP assay revealed an approximately 1.49-fold enrichment of NF-κB of the variant type TT when compared to that of the wild-type GG in rs9395890 (P = 0.027; TT = 3.20 ± 0.16, GT = 2.81 ± 0.20, GG = 1.71 ± 0.18). The luciferase reporter assay showed that the NF-κB binding site activity in T allele was slightly higher than that in G allele, though it is not significant. CONCLUSIONS: Our findings indicate that rs9395890 is associated with susceptibility to ESRD in Taiwan population.

A predictive model for progression of CKD.

The prevalence of chronic kidney disease (CKD) in Taiwan is 11.9%, and the incidence and prevalence of end-stage renal disease (ESRD) is ranked first in the world. The severity of CKD progression to ESRD is dependent on glomerular filtration rate and proteinuria. However, the risk factors for ESRD also include diabetes, hypertension, hyperlipidemia, age, sex, and so on, and predicting CKD progression using few variables is insufficient. Currently, there are no models with high accuracy and high explanatory power that could predict the risk of progression to dialysis in CKD patients in Taiwan. Our aim was to establish an optimal prediction model for CKD progression in patientsThis study was a retrospective cohort study, which reviewed data from the "Public health insurance Pre-ESRD preventive program and patient health education program" that was implemented by the National Health Insurance Administration, Ministry of Health and Welfare. From 2006 to 2013, data of CKD patients from the Tri-Service General Hospital in Neihu District, Taipei City was examined. The data collected in this study included demographic variables, past medical history, and blood biochemical values. After exclusion of variables with >30% missing data, the remaining variables were interpolated using multiple imputations and inputted into the prediction model for analysis. The Cox proportion hazard model was used to investigate the influence of CKD risk factors on progression to dialysis. The strengths of various models were evaluated using likelihood ratios (LR), in order to identify a model which uses the least factors but has the strongest explanatory power.The study results included 1549 CKD patients, of whom 1017 eventually had dialysis. This study found that in the prediction model with the best explanatory power, the influencing factors and hazard ratios (HR) were: age 0.95 (0.91-0.99), creatinine 1.03 (1.02-1.05), urea nitrogen 1.18 (1.14-1.23), and comorbid systemic diabetes 1.65 (1.45-1.88).A prediction model was developed in this study, which could be used to carry out predictions based on blood biochemical values from patients, in order to accurately predict the risk of CKD progression to dialysis.

The increase in total knee replacement surgery in Taiwan: A 15-year retrospective study.

Total knee replacement (TKR) is considered as one of the most success among clinical interventions for patients with who suffering from knee osteoarthritis (OA). We sought to estimate the incidence of TKR using demographics, incidence rates, lengths of hospital stay, and costs from 1996 to 2010 by analyzing Taiwan's National Health Insurance Research Database. A total of 154,553 patients obtained primary TKR surgery between 1996 and 2010. The diagnosis code for knee OA and the procedure code for TKR were selected from the records. To compare the rate of TKR between covariables, we calculated the TKR risk ratios and 95% confidence interval (CI) of these variables (gender, age, age group, and primary diagnoses). A 2-tailed P-value of .05 was considered statistically significant. The statistical package SPSS version 20.0 (SPSS, Chicago, IL) was used to conduct all the statistical analyzes. We analyzed 154,553 TKRs performed by surgeons in Taiwan from 1996 to 2010. The overall crude incidence increased from 26.4 to 74.55 TKR per 100,000 inhabitants from 1996 to 2010. TKR incidence for the 70 to 79 years age group increased from 227 to 505 per 100,000 people from 1996 to 2010. The age-standardized rate ratios for TKR of women to men ranged from 2.5 to 3.0. The mean average length of stay in hospital was 15 days in 1996 and decreased to 8 days in 2010. During the study period, the adjusted mean cost per patient decreased from US$7485 to US$4827. Health expenditures for TKR were 5% of total National Health Insurance expenditure every year. Over the 15-year period, Taiwan's TKR incidence tripled, which is consistent with population ageing. Arthritis will be a major public health issue in the ageing population in the future.

No difference in the functional improvements between unilateral and bilateral total knee replacements.

BACKGROUND: Differences between staged bilateral total knee replacement (TKR) and simultaneous bilateral TKR have been investigated, but few studies have investigated differences in the functional improvements resulting from these methods. Therefore, this study investigates the different functional improvements between staged bilateral total knee TKR and simultaneous bilateral TKR. METHODS: Among 144 potential bilateral TKR patients who were included in this study, 93 (64.6%) patients selected unilateral TKR and 51 (35.4%) selected bilateral TKR. Functional improvements were assessed using the Western Ontario and McMaster University osteoarthritis index (WOMAC) and the Medical Outcomes Trust Short Form-36 (SF-36), and patients were interviewed pre-operatively and after 6 months. A generalized equation was used to test for differences in functional improvements. RESULTS: After TKR, pain, stiffness, function and total WOMAC scores were significantly reduced in both groups, with mean changes from - 26.6 to - 41.4 and from - 27.5 to - 42.2.The mean health change of SF-36 scores, physical component and mental component scores changed to 45.2 ± 18.2, 74.0 ± 15.4 and 77.0 ± 9.6, respectively, in Group 1 and 47.1 ± 17.1, 74.0 ± 15.2 and 75.5 ± 12.1, respectively, in Group 2. Unilateral and simultaneous bilateral TKR produce similar functional improvements, although current work status may be a novel impact factor. CONCLUSION: No differences in functional improvements were identified between patients who selected unilateral versus bilateral TKR, indicating no recommendation for one procedure over the other.