Linc279227 contributes to mitochondrial dysfunction in high glucose-treated mouse renal tubular epithelial cells.

BACKGROUND: The aberrant expression of long noncoding RNAs (lncRNAs) has been associated with diabetic nephropathy (DN), a major complication of diabetes mellitus (DM). This study investigated the differential expression of lncRNAs in DM without renal damage and DM with renal damage, known as DN, and elucidated the functions of a pathogenic lncRNA. METHODS: High-throughput sequencing was performed on the kidneys of male db/db mice with kidney injury, db/db mice without kidney involvement and db/m control littermates. Linc279227 expression was confirmed by RT‒qPCR and fluorescence in situ hybridization. The effects of linc279227 on high glucose (HG)-treated renal tubular epithelial cells (RTECs) were evaluated by autophagy flux monitoring, Western blot determination and mitochondrial morphological detection. RESULTS: With high-throughput sequencing, we identified a 1024 nt long intergenic noncoding RNA, TCONS_00279227 (linc279227), whose expression was markedly increased in the kidneys of db/db mice with kidney injury compared to db/db mice without kidney injury and db/m control littermates. Fluorescence in situ hybridization confirmed that linc279227 was mainly located in the renal tubules of mice with DN. In vitro, linc279227 expression was found to be significantly increased in RTECs treated with high glucose (HG) for 48 h. Silencing linc279227 markedly restored the levels of autophagy-/mitophagy-associated proteins in HG-stimulated RTECs. Furthermore, silencing linc279227 reduced phosphorylated Drp1 expression and increased Mfn2 expression in RTECs exposed to HG. CONCLUSION: Our data suggest that linc279227 plays an important role in mitochondrial dysfunction in HG-treated RTECs and that silencing linc279227 rescues RTECs exposed to HG.

Prognostic Value of Hemoglobin Concentration on Renal Outcomes with Diabetic Kidney Disease: A Retrospective Cohort Study.

Objective: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated. Methods: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin. Results: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521±22.960 g/L. The median follow-up time was 21.103±18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males. Conclusion: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.

Development and validation of a simple equation to evaluate dietary protein intake using the blood urea nitrogen/serum creatinine ratio in patients with stage 3 chronic kidney disease.

PURPOSE: The aim of this research was to develop a simple equation to evaluate dietary protein intake (DPI) in patients with stage 3 chronic kidney disease (CKD) using the blood urea nitrogen (BUN)/serum creatinine (SCr) ratio (BUN/SCr). METHODS: In a prospective cohort of 136 inpatients with stage 3 CKD from 2 centres, the estimated dietary protein intake (DPI) was calculated using Maroni's formula after the patients implemented a 7 day protein-restricted diet. We developed estimation equations based on BUN/SCr and the spot urinary urea nitrogen (UUN)/urinary creatinine (UCr) ratio (UUN/UCr) in combination with sex and body mass index (BMI). These equations were then internally and externally validated. RESULTS: The following candidate parameters were derived from univariate regression analysis for 5 established models: sex, BMI, BUN/SCr, UUN and UUN/UCr. Sex and BMI were included in all models after variable evaluation using multiple regression analysis. UUN, UUN/UCr and BUN/SCr were included in model 3, model 4 and model 5, respectively. Both internal and external validation indicated that model 5 resulted in the lowest values for bias and root mean square error and the highest P30 compared with model 3 and model 4. Therefore, the model 5 equation, DPI = - 5.18 (- 14.49 if the patient is female) + 1.89 × BMI + 1.38 × BUN/SCr, was selected because of the higher correlation (r = 0.498) between the estimated DPI and predicted DPI. CONCLUSION: The DPI equation developed using BUN/SCr, sex and BMI may be used to estimate protein intake for patients with stage 3 CKD. TRIAL REGISTRATION: Chinese Clinical Trial Registry Center (ChiCTR-ROC-17011363). Registered on 11 May 2017, Retrospectively registered, http://www.chictr.org.cn/index.aspx .