Remnant cholesterol and the risk of diabetic nephropathy progression to end-stage kidney disease in patients with type 2 diabetes mellitus: a longitudinal cohort study.

AIM: Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease (ESKD). Remnant cholesterol has been investigated as a predictor for the progression of DN in type 1 diabetes mellitus patients, as well as the incidence of DN in type 2 diabetes mellitus (T2DM) patients. This study aimed to evaluate the longitudinal relationship between baseline remnant cholesterol and kidney outcomes using a Chinese T2DM with biopsy-confirmed DN cohort. METHODS: We included 334 patients with T2DM and biopsy-confirmed DN during 2010-2019 West China Hospital T2DM-DN cohort. Remnant cholesterol was defined by Martin-Hopkins equation. Patients were divided into four groups based on the median (IQR) remnant cholesterol concentration at the time of renal biopsy. The kidney outcome was defined as ESKD, which was defined as the need for chronic kidney replacement therapy or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2. The relationship between remnant cholesterol and kidney outcome was analyzed using the Kaplan‒Meier method and Cox regression analysis. RESULTS: The mean age was 51.1 years, and 235 (70%) were men. During follow-up, a total of 121 (36.2%) patients reached ESKD. The Kaplan‒Meier analysis showed that patients in the highest quartile (quartile 4) group had lower cumulative renal survival (log-rank test, p = 0.033) and shorter median renal survival time [34.0 (26.4-41.6) vs. 55.0 (29.8-80.2) months] than patients in the lowest quartile (quartile 1) group. By univariate analysis, the high remnant cholesterol group was associated with a higher risk of progression to ESKD. Moreover, the risk of progression to ESKD in the highest quartile was still 2.857-fold (95% CI 1.305-6.257, p = 0.009) higher than that in the lowest quartile, and one-SD increase of remnant cholesterol was associated with a higher risk (HR = 1.424; 95% CI 1.075-1.886, p = 0.014) of progression to ESKD, after adjusted for confounding factors. CONCLUSIONS: High remnant cholesterol is independently associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive marker of ESKD. CLINICAL RELEVANCE: Calculated remnant cholesterol has the advantages of being economical and clinically accessible. Moreover, to our knowledge, there are no longitudinal cohort studies for investigating the risk of progression of T2DM-DN to ESKD. In our study, higher remnant cholesterol was associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive predictor of ESKD.

Impact of non-alcoholic fatty liver disease and fibrosis on mortality and kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A multi-cohort longitudinal study.

AIM: To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. METHODS: Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. RESULTS: In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. CONCLUSIONS: In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.

A review regarding the article 'Diabetic peripheral neuropathy is associated with diabetic kidney disease and cardiovascular disease: The silesia diabetes-heart project'.

One of the most common micro vascular complications of diabetes is diabetic peripheral neuropathy (DPN). The well-recognized risk factors for DPN are hyperglycemia, dyslipidemia, and hypertension. DPN is associated with a high mortality rate and poor prognosis. Its pathogenesis is not fully understood, and clinical treatment is focused on relieving its clinical symptoms, as well as improving blood sugar control and cardiovascular risk factors. DPN and its clinically effective treatments need to be studied. Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of cardiovascular disease. Prevention and management strategies should focus on lifestyle modification, education and awareness, systematic screening for early complications, and intensive management of modifiable risk factors. There was an association between DPN and DKD as well as CVD, BMI and age demonstrated. These may indicate that in case of having one diabetes complication diagnosed, it is important to screen for others, including macrovascular ones, as they may be undiagnosed due to their "silent" nature. Further studies are expected to strengthen basic research on the subject, reveal modern medical mechanisms, and provide fresh ideas and innovative methods for the treatment of DPN.

Comparative effectiveness of seven interventions for chronic hepatitis D: a systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs, and Placebo] to treat chronic hepatitis D. METHODS: We followed PRISMA-NMA guidelines, searched databases (Cochrane Library, PubMed, EMBASE, and Web Of Science) for eligible randomized controlled trials (RCTs), and applied STATA17.0 software to execute the meta-analysis. RESULTS: We included 14 randomized controlled trials (814 patients) comparing seven different interventions. The results of the network meta-analysis showed that: ① Sustained virological response (after 24 weeks of follow-up): Four intervention groups (BLV + IFN, IFN alone, IFN + NAs, and NAs alone) were effective (relative risk (RR) = 13.30, 95% confidence interval (Cl) [1.68,105.32], RR = 12.13, 95% Cl [1.46,101.04], RR = 5.05, 95% Cl [1.68,15.19], RR = 5.03, 95% Cl [1.66,15.20]), with no statistically significant differences between the four groups. The top three in probability rankings were: BLV + NAs, BLV + IFN, and BLV alone (surface under the cumulative ranking curve (SUCRA) = 86.8%, 80.3%, and 48.4%; ② Sustained biochemical response (after 24 weeks of follow-up): BLV + IFN and IFN were superior to BLV (RR = 14.71, 95% Cl [1.14,189.07], RR = 16.67, 95% Cl [1.39,199.52]). The top three were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 86.9%,81.2%, and 64.3%). ③ Histological response: NAs were superior to BLV (RR = 2.08, 95% Cl [1.10,3.93]), whereas the difference between other treatment regimens was not statistically significant, and the top three in the probability ranking were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 75.6%, 75.6%, and 61.8%). CONCLUSIONS: IFN, IFN + BLV, and IFN + NAs were effective in clearing HDV RNA and normalizing alanine aminotransferase levels; however, IFN and IFN + NAs had a high rate of viral relapse at 24 weeks post-treatment follow-up. There was no additional benefit of adding NAs to IFN therapy for chronic hepatitis D; however, the combination of IFN + BLV significantly improved short-term HDV RNA clearance, which showed strong synergistic effects. The seven regimens included in the study did not contribute significantly to liver histological improvement. Therefore, the IFN + BLV combination has the most potential as a treatment option to improve the long-term prognosis or even cure chronic hepatitis D. TRIAL REGISTRATION: This systematic evaluation and meta-analysis was registered with PROSPERO under the registration number: CRD42022314544.).

Associations of lactate dehydrogenase with risk of renal outcomes and cardiovascular mortality in individuals with diabetic kidney disease.

OBJECTIVE: This study aimed to investigate the role of the lactate dehydrogenase (LDH) in the development of end-stage renal disease (ESRD) and the cardiovascular mortality in individuals with diabetic kidney disease (DKD). METHODS: Two cohorts were recruited in this study. We explored the correlation between LDH and renal injury in individuals with DKD in using a Cohort 1. Additionally, we validated this correlation in the NHANES database and further investigated its association with the risk of cardiovascular mortality in Cohort 2 which also comprised individuals with DKD. RESULTS: In cohort 1, multivariate Cox regression analysis demonstrated that individuals in DKD with higher LDH were independently associated with an increased risk of ESRD compared to those with lower LDH (HR = 2.11; 95 % CI, 1.07-4.16). In cohort 2, linear regression models showed that LDH affects the level of albumin-creatinine ratio (ACR) (ß = 2.95, P = 0.001). Additionally, multivariate Cox regression analysis results showed that an increase in LDH per 1-standard deviation (SD) was associated with a 27 % increased risk of cardiovascular mortality (HR = 1.27; 95 % CI, 1.09-1.48). CONCLUSIONS: LDH levels are associated with renal injury and progression to ESRD, as well as being an independent risk factor for cardiovascular in individuals with DKD.

Circulating microRNA-145 as a diagnostic biomarker for non-small-cell lung cancer: A systemic review and meta-analysis.

BACKGROUND: MicroRNAs (miRNAs), a class of small non-coding, highly stable RNAs, have been reported to have diagnostic value for variety types of cancers. OBJECTIVES: To assess the diagnostic value of circulating miR-145 for non-small cell lung cancer (NSCLC) by using systemic review and meta-analysis. METHODS: A systematic literature search was conducted in five databases until 20 February 2020 to identify diagnostic trials of miR-145 in the diagnosis of NSCLC. The quality of included studies was assessed by the QUADAS-2 tool with Review Manager 5.3, and the summary receiver operating characteristic (SROC) curve was plotted by STATA 13.1 software. RESULTS: A total of 1394 patients from 11 data sets in trials (published in nine studies) were recruited. The area under the curve of the SROC was 0.83. According to the meta regression, the specimen selection was considered the source of heterogeneity, the SROC in serum (0.90 (95% CI 0.87, 0.92), the sensitivity was 0.84 (95% CI 0.79, 0.89), and the specificity was 0.80 (95% CI 0.71, 0.89)) was obviously higher than that in plasma (SROC=0.75). CONCLUSION: Serum miR-145 might be served as a potentially useful biomarker for NSCLC diagnosis. However, due to the existing limited-quality research, more large-scale and multicenter studies are required for further verification.