Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity.

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

Efficacy and safety of non-steroidal mineralocorticoid receptor antagonists for renal outcomes: A systematic review and meta-analysis.

BACKGROUND: Novel nonsteroidal mineralocorticoid receptor antagonists (MRAs) are noted for their potential cardiorenal benefits for patients with type 2 diabetes mellitus and chronic kidney diseases; however, the effect of this regimen on renal outcomes remains uncertain. METHODS: We performed a systematic review and meta-analysis of nonsteroidal MRAs focusing primarily on renal outcomes and safety in randomized, controlled trials. The MEDLINE, Embase, and Cochrane databases were systemically searched for trials published through April 2022. We included randomized, controlled trials assessing the effects of nonsteroidal MRAs on renal outcomes, as well as cardiovascular disease (CVD) effects in patients with chronic kidney disease (CKD). Summary estimates of risk ratios (RRs) reductions were calculated with a random-effects model. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. This study is registered with PROSPERO under number CRD42022335464. FINDINGS: In total, 11 trials and 1 pooled analysis including a total of 17,517 participants were enrolled. Nonsteroidal MRAs reduced renal composite endpoints by 17 % [HR = 0.83, 95 % (0.75, 0.91); low quality] with 16 % in kidney failure (high quality), 23 % in ESRD (high quality), 20 % in eGFR decreased to less than 15 mL/min/1.73 m2 (high quality), and 17 % with more than a 40 % decrease in eGFR (high quality); 14 % with cardiovascular composite endpoints [HR = 0.86, 95 % (0.78, 0.94); moderate quality]; and 13 % of all-cause mortality [HR = 0.87, 95 % (0.76, 0.98); moderate quality]. Nonsteroidal MRAs were also associated with additional benefits in lowering UACR levels (moderate quality) and lowering BP levels (moderate quality) compared with the control groups. However, nonsteroidal MRAs did not show a statistically significant effect on the risk of renal death (moderate quality), hospitalization for any cause (moderate quality) or change in GFR (low quality). Regarding safety, there was no significant difference in the risk of adverse events between the participants receiving nonsteroidal MRAs and the control group. INTERPRETATION: Nonsteroidal MRAs had a statistically beneficial effect on reducing the risk of the composite kidney outcome, the composite of cardiovascular outcomes, and all-cause mortality. Nonsteroidal MRAs were also associated with benefits of proteinuria remission and blood pressure lowering. Although these findings provided positive evidence for the use of nonsteroidal MRAs for cardiorenal protection in patients with or without CKD, the quality of this evidence is potentially uncertain.

High expression of M3 muscarinic acetylcholine receptor is a novel biomarker of poor prognostic in patients with non-small cell lung cancer.

We assessed the expression of M3 receptor in non-small cell lung cancer (NSCLC) and determined its relationship with clinicopathological features and its impact on patient outcome. Specimens from 192 patients with NSCLC were investigated by immunohistochemistry for M3 receptor and Ki67 expression. Correlation between the expression of M3 receptor and Ki67 and various clinicopathological features of NSCLC patients was analyzed. We found that M3 receptor expression was gradually elevated from normal to metaplasia/dysplasia tissues to cancer tissues. Furthermore, there was a similar trend for Ki67 expression. Statistical analysis revealed that M3 receptor expression in tumor cells were correlated significantly with stage (P < 0.0001), histology type (P = 0.0003), Ki67 expression (P < 0.0001), tumor size (P < 0.0001), lymph node status (P < 0.0001), LVS invasion (P = 0.0002), and histology grade (P < 0.0001). Patients with M3 receptor high expression showed far lower disease-free survival (DFS) and overall survival (OS) rates than those with M3 receptor low expression. Multivariate Cox regression analysis demonstrated that high M3 receptor expression was an independent prognostic factor for both DFS and OS. High M3 receptor expression correlates with poor survival in NSCLC patients. M3 receptor expression may be related with tumor progression in NSCLC, indicating that M3 receptor may be a novel antineoplastic target in the future.