Kidney Diseases最新文献

Introduction: Emerging evidence suggests a potential association between dyslipidemia and renal dysfunction. Remnant cholesterol, defined as the cholesterol content of triglyceride-rich lipoproteins, has not been thoroughly investigated in relation to rapid renal function decline in individuals with preserved kidney function. Therefore, our study aimed to clarify this association in a nationwide Chinese cohort.

Methods: Our study used data from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study. Remnant cholesterol level was derived using the following equation: total cholesterol minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol. The study outcomes were rapid kidney function decline or the progression to chronic kidney disease (CKD). To determine the associations between remnant cholesterol and CKD outcomes, we used multivariable logistic regression, subgroup analyses, restricted cubic spline models, and receiver operating characteristic curve analysis.

Results: A total of 4,039 individuals (59 ± 8.7 years, 52.5% female) were enrolled in our study. Over a 4-year follow-up, 195 (4.8%) individuals experienced rapid renal function decline, and 367(9.1%) individuals experienced progression to CKD. Elevated remnant cholesterol levels were strongly linked to an elevated risk of rapid renal function decline (OR = 1.89, 95% CI: 1.59-2.26, p value <0.001) and the progression to CKD (OR = 1.76, 95% CI: 1.51-2.04, p value <0.001). The restricted cubic spline analysis revealed that these associations were nonlinear. Additionally, subgroup analysis demonstrated that this relationship was more evident in individuals with LDL-C >2.6 mmol/L than those in LDL-C ≤2.6 mmol/L.

Conclusion: Our study demonstrated that elevated remnant cholesterol concentrations were associated with a higher risk of rapid renal function decline among middle-aged and older Chinese adults. These findings suggest that remnant cholesterol may serve as a valuable biomarker for identifying individuals at elevated risk for renal dysfunction.

Background: The SET and MYND domain-containing (SMYD) protein family is a group of lysine methyltransferases with SET and MYND domains and plays a critical role in regulating gene expression through the methylation of histone and non-histone proteins.

Summary: Studies have linked mutations or overexpression of SMYD2 and SMYD3 to various cancers, including renal carcinoma. Recent research also demonstrates that the expression levels and activity of SMYD2 and SMYD3 are increased in animal models of renal diseases such as autosomal dominant polycystic kidney disease, renal fibrosis, and diabetic nephropathy. Inhibiting either SMYD2 or SMYD3 pharmacologically or genetically can effectively suppress renal tumorigenesis and cystic formation while improving outcomes in renal fibrosis and diabetic nephropathy. Additionally, SMYD2 and SMYD3 are involved in the pathogenesis of acute kidney injury.

Key messages: This review summarizes the roles of these two lysine methyltransferases in renal diseases, highlights their mechanisms, and emphasizes their potential as therapeutic targets for kidney disorders.

Introduction: There is a close relationship between oxidative stress and renal ischemia-reperfusion injury (RIRI). Dihydroquercetin (DHQ, also known as Taxifolin) can reduce kidney damage, and suppress cellular damage caused by oxidative stress. This study aimed to investigated the effects and underlying mechanisms of DHQ on RIRI.

Methods: First, hypoxia/reoxygenation (H/R) treated HK-2 cells were used for RIRI in vitro experiments, and the dosage of DHQ was selected by observing cell viability and lactate dehydrogenase release. The protective effects of DHQ were evaluated by detecting cell apoptosis, reactive oxygen species (ROS) levels, and oxidative stress indicators levels.

Results: Our data suggested that DHQ inhibited cell apoptosis, ROS levels, and oxidative stress of H/R treated HK-2 cells. PIM2 regulates cell survival and proliferation, and H/R treatment upregulated PIM2 levels. Over-expression of PIM2 partly reversed the effects of DHQ on protecting HK-2 cells after H/R induction, and promoted RIPK2 phosphorylation mediated NF-κB p65 signaling pathway. Additionally, METTL3 is an N⁶-methyladenosine (m⁶A) writer, and DHQ suppressed its expression in H/R treated HK-2 cells. METTL3 was enriched in PIM2 mRNA by m⁶A modification and stabilized the expression of PIM2. As for in vivo experiments, DHQ also inhibited the PIM2 level in mice kidney tissues and alleviated the kidney damage caused by RIRI. These effects were manifested in the reduction of renal injury markers, the reduction of oxidative stress levels, and the results of renal tissue hematoxylin-eosin staining. DHQ also suppressed PIM2 mediated RIPK2 phosphorylation mediated NF-κB p65 signaling pathway in renal tissues.

Conclusion: Taken together, DHQ inhibited PIM2 levels by suppressing METTL3 mediated m⁶A modification to protect HK-2 cells from H/R induced injury, and this may be related to the regulation of PIM2 on RIPK2 phosphorylation mediated NF-κB p65 signaling pathway. This study suggested that DHQ may be a promising drug to treat RIRI, and may be useful for finding effective therapeutic targets in RIRI.

Background: Artificial intelligence (AI) has made significant advances in nephrology, revolutionizing the diagnosis, prognosis, and treatment of kidney diseases.

Summary: This review provides an overview of AI applications in nephrology, introducing the basic structures of each model, highlighting both traditional machine-learning approaches and neural networks, and providing model application comparisons along with selection recommendations. It discussed key challenges in deciding appropriate AI models for specific tasks and evaluated their advantages, limitations, and optimal use cases. Current applications of AI in nephrology mainly include diagnosis and disease outcome prediction, medical image analysis, treatment recommendations, and personalized health management, supported by massive electronic health records and multimodal data integration. Traditional machine learning models perform well on datasets of varying sizes and structures, while neural networks excel at handling complex and imaging data. Emerging hardware innovations are expected to improve the performance of neural network models, enabling more accurate diagnosis and automated analysis in clinical practice. In the future, AI will have great potential to advance individualized patient care and enable real-time data processing in nephrology.

Key messages: An overview of AI applications in nephrology is provided in this review.

Introduction: Vascular calcification, linked to atherosclerosis, is a significant cardiovascular risk factor in chronic kidney disease (CKD). While different intracranial carotid arteriosclerosis subtypes affect stroke risk in the general population, their prevalence, causes, and impact on CKD patients remain unclear.

Methods: This cohort study used data from the National Taiwan University Hospital's pre-end-stage renal disease care database, including 2,622 CKD patients with brain CT scans from 2006 to 2020. Intracranial carotid artery calcifications were categorized as intimal or internal elastic lamina (IEL) subtypes. Multivariable Cox regression assessed the associations between each calcification subtype and incident stroke or vascular mortality.

Results: Among 2,622 patients, 2,470 (94.2%) had calcifications classifiable as intimal (n = 719, 27.4%), IEL (n = 1,642, 62.6%), or mixed (n = 109, 4.2%) subtypes. Multivariable analysis revealed that IEL subtype was associated with older age, diabetes, prior vascular diseases, and impaired renal function (p < 0.05). Over a median follow-up of 3.9 years, IEL subtype exhibited a higher risk of any stroke (adjusted hazard ratio [HR] [95% CI]: 2.0 [1.2-3.2], p = 0.007) and vascular death (adjusted HR [95% CI]: 2.0 [1.4-3.0], p < 0.001), compared to those without calcification. Furthermore, the IEL subtype displayed a higher risk of any stroke (adjusted HR [95% CI]: 1.6 [1.1-2.3], p = 0.017) and vascular death (adjusted HR [95% CI]: 1.6 [1.3-2.1], p < 0.001) compared to the intimal subtype.

Conclusion: IEL calcification is prevalent in CKD patients and associated with aging, diabetes, and impaired renal function. It poses a higher risk of cerebrovascular events compared to those without calcification or with intimal calcification.

Introduction: Despite the reported connection between different combinations of the standard MetS criteria and chronic kidney diseases (CKDs), most data raise significant concerns about its predictive usefulness in clinical settings beyond its components. Metabolic syndrome severity, expressed by the continuous metabolic syndrome severity score (cMetS-S), is a more applicable health metric that may more accurately predict future health outcomes. However, no evidence is known about the association between the trajectory of cMetS-S and the development of CKD.

Methods: In the population-based Tehran Lipid and Glucose Study, 4,462 participants aged 20-60 years free of CKD at baseline were included and followed at 3-year intervals. We examined the trajectories of cMetS-S over 9 years (1999-2009) using latent growth mixture modeling and subsequent risks of incident CKD 8 years later (2010-2018). The prospective association of identified trajectories with CKD was examined using the Cox proportional hazard model adjusting for age, sex, education, and family history of diabetes, physical activity, obesity (BMI ≥30 kg/m²), antihypertensive, and lipid-lowering medication, and baseline fasting plasma glucose in a stepwise manner.

Results: Three cMetS-S trajectory groups of low (28.3%), medium (50.0%), and high (21.7%) were identified during the exposure period. High cMetS-S trajectory pattern was associated with increased risk of CKD adjusting for age, sex, education, smoking, physical activity, baseline estimated glomerular filtration rate, and even after further adjustment for MetS components (1.32; 95% CI: 1.04-1.67). The associated risk remained significant even in normoglycemic, nonobese, and non-hypertensive individuals. Sex-specific subgroup analysis showed that MetS severity score is associated with CKD only in men.

Conclusion: The trend of cMetS-S over time is associated with the development of CKD, even in those without major risk factors, for example, obesity, diabetes mellitus, and hypertension. It could be clinically helpful in identifying individuals at elevated risk rather than stating it as a predictive or causative factor. It could be clinically beneficial in identifying and tracking individuals at elevated risk rather than stating it as a predictive or causative factor.

[This corrects the article DOI: 10.1159/000520586.].

Introduction: This study aimed to evaluate whether supplementation of finerenone to renin-angiotensin system inhibitor (RASi) therapy confers additional renoprotective benefit versus RASi therapy only in clinical IgA nephropathy (IgAN).

Methods: Primary IgAN patients administered RASi therapy at Ruijin Hospital from January 2023 to December 2023 were retrospectively enrolled, with an estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m². IgAN patients treated with steroids or immunosuppressants were excluded. The analyzed patients were divided into the finerenone and RASi groups based on finerenone use status. Patients were selected via 1:1 propensity score matching (PSM) based on age, sex, 24-hour urine protein, eGFR, and sodium-dependent glucose transporter-2 inhibitor (SGLT2i) use status. The primary endpoint was the change in urinary protein at 9 months compared to baseline. Secondary endpoints included eGFR decline and safety outcomes, with additional data collection at 12 months.

Results: After PSM, 62 patients were included, with 31 in each group. The finerenone group showed a greater reduction in urinary protein (-29.03% vs. 41.47%, p < 0.001) and a slower least squares mean eGFR slope (1.87 vs. -4.13 mL/min/1.73 m², p = 0.03) at 9 months compared with the RASi group. Subgroup analysis suggested a trend toward greater improvement with SGLT2i addition, but the interaction was not statistically significant (p = 0.31), likely due to the limited sample size. Extended follow-up at 12 months confirmed these findings, demonstrating a sustained reduction in proteinuria (p = 0.001). Hyperkalemia rates remained similar in both groups at 4, 9, and 12 months.

Conclusions: The combination of finerenone with RASi is associated with a greater reduction in urinary protein and potentially better stabilization of eGFR compared with RASi alone in IgAN patients. However, these findings require further validation in prospective studies.

Introduction: In FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials, finerenone reduced the risk of cardiovascular (CV) and kidney events versus placebo in patients with type 2 diabetes and chronic kidney disease, on optimized renin-angiotensin system blockade. This FIDELITY post hoc subanalysis explores the efficacy and safety of finerenone in Asian patients.

Methods: For this subanalysis, efficacy outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decrease from baseline over ≥4 weeks or renal death) outcome. A change in urine albumin-to-creatinine ratio (UACR) from baseline to month 4 and eGFR slopes was also assessed. All outcomes were assessed by baseline eGFR (<60 and ≥60 mL/min/1.73 m²) and UACR (<300 and ≥300 mg/g) subgroups. Safety outcomes were reported as treatment-emergent adverse events, including laboratory evaluations for hyperkalemia.

Results: In the Asian subpopulation, 1,412/2,858 (49.4%) received finerenone. Finerenone-treated Asian patients had a lower risk of the composite CV outcome (hazard ratio [HR] = 0.90; 95% confidence interval [CI], 0.70-1.15) and nominally significant reductions in the risk of ≥57% and ≥40% eGFR composite kidney outcomes (HR = 0.64; 95% CI, 0.50-0.82 and HR = 0.67; 95% CI, 0.56-0.80, respectively) versus those receiving placebo, irrespective of baseline eGFR and UACR. Data on change of eGFR from baseline over the course of the trials indicated that chronic kidney disease progression in Asian patients was slower with finerenone versus placebo. Overall, safety outcomes were balanced between both populations. Serum potassium values with finerenone were similar between the Asian and non-Asian subpopulations (>5.5 mmol/L: 15.6% versus 17.1%; >6.0 mmol/L: 4.6% versus 2.9%, respectively), while hyperkalemia leading to permanent treatment discontinuation with finerenone was low in both populations (Asian: 1.5%; non-Asian: 1.8%).

Conclusion: Finerenone reduced the risk of CV and kidney events and demonstrated a well-tolerated safety profile in the FIDELITY Asian subpopulation.