Renal Failure最新文献

Aims: To validate the effectiveness of intensive glycemic control in preventing acute kidney injury (AKI) among patients with coronary artery disease (CAD) and prediabetes.

Methods: This investigation employed data from the Prospective Registry of the Current Status of Care for Patients with CAD database. Glycemic control was evaluated using the time-weighted average glucose (TWAG) and the glucose coefficient of variation (CV) for each participant. The primary outcome was AKI occurrence.

Results: A total of 2,454 CAD patients with prediabetes were included between January 2022 and June 2023. The mean age was 62.6 ± 10.3 years, with 27.1% female. In univariate analysis, each 1 mmol/L increase in TWAG was associated with a 1.51-fold (95% confidence interval (CI): 1.36-1.68) higher incidence of AKI. After stepwise adjustment for covariates, the odds ratio (OR) remained significant at 1.50 (95% CI: 1.35-1.67). Similarly, glucose CV showed a positive correlation with AKI risk; a 0.1-unit increase in CV was linked to approximately a 44% higher risk. When both TWAG and CV were included simultaneously in the model, each maintained an independent positive association with AKI. Restricted cubic spline analyses revealed a dose-dependent increase in AKI risk with rising TWAG and CV. Subgroup analyses confirmed the positive relationship between TWAG, glucose variability, and AKI risk.

Conclusions: Our study reveals an association between TWAG or CV of glucose and AKI in individuals with both CAD and prediabetes. These findings highlight the potential value of continuous glucose monitoring and managing glycemic variability to reduce AKI risk in this population.

Background: Traditional Chinese medicine active ingredients have been increasingly recognized for their pivotal role in the treatment of acute kidney injury (AKI).

Methods: This study aimed to investigate the reno-protective effects and underlying mechanisms of 4-Methoxylonchocarpin (4ML), an extract from Abrus precatorius Linne, in a cisplatin-induced AKI model. Kidney injury was assessed through a comprehensive evaluation of renal function indicators and histopathological changes. The impact of 4ML on ferroptosis and AMPK pathways was examined by measuring lipid peroxidation biomarkers and iron ion following low and high dose 4ML treatments in mice. In vitro experiments, using HK-2 cells to assess ferroptosis biomarkers and cell proliferation with or without 4ML treatment, and in the presence of selective inhibitors or activators of ferroptosis and AMPK, to elucidate the potential mechanisms.

Results: 4ML administration significantly attenuated cisplatin-induced AKI in both mice models and HK-2 cells. Mechanistic studies revealed that 4ML treatment markedly reduced ferroptosis and activated the AMPK pathway, as evidenced by altered expression levels of GSH, GPX4, MDA, LPO, and iron ions. The activation of AMPK pathway by 4ML contributed to the amelioration of AKI. Conversely, the induction of ferroptosis and inhibition of AMPK attenuated the protective effects of 4ML.

Conclusion: These findings suggest that 4ML as a promising therapeutic agent for cisplatin-induced AKI, primarily through inhibiting ferroptosis and regulating AMPK. This study provides further evidence supporting the potential of traditional Chinese medicine-derived compounds in the management of AKI.

While nephronophthisis (NPHP) classically manifests as mild tubular proteinuria, emerging evidence reports nephrotic-range proteinuria with edema. This study aims to explore the phenotypes and genotypes of pediatric NPHP patients with different levels of proteinuria. Twenty-one children with NPHP were recruited into this single-center cohort. They were divided into two groups according to proteinuria levels: group A (mild proteinuria, n = 12) and group B (moderate-to-heavy proteinuria, n = 9). The median age at symptom onset was 7.4 years (IQR 2.4-12.8). By the end of follow-up, 20 patients had progressed to ESRD at a median age of 9.8 years (IQR 5.8-12.9). Patients in group B exhibited significantly higher prevalence of family histories, hypertension, edema, and higher urine microalbumin-to-α1-microglobulin (MA/A1M) ratios. Genetic testing identified NPHP1 mutations as the most prevalent (61.9%), followed by TTC21B variants (19.0%). However, TTC21B mutations were more commonly found in group B (3/4, 75.0%) with one homozygous mutation and two compound heterozygous mutations. Five novel mutations of NPHP genes were identified. Further literature review of patients with TTC21B gene mutations revealed that the P209L variant was almost present in all North African/European patients, while the C518R heterozygous mutation occurred in 72.7% of Asian patients. In conclusion, NPHP remains a diagnosis in patients presenting with moderate-to-heavy proteinuria, particularly when accompanied by characteristic features including positive family history, hypertension, and edema, with TTC21B emerging as the predominant pathogenic gene in this clinical subgroup.

Recent studies have closely linked estimated glucose disposal rate (eGDR) to cardiovascular events; however, research on eGDR in chronic kidney disease (CKD) is limited. This study aimed to explore the relationship between eGDR and kidney diseases, including rapid kidney function decline (RKFD) and new-onset CKD (NOCKD), in a non-CKD population. We examined 5,679 non-CKD individuals from the China Health and Retirement Longitudinal Study (2011-2015) with complete eGDR data. Participants were categorized into four groups based on eGDR quartiles. Logistic regression and restricted cubic spline (RCS) were utilized to assess the correlation between eGDR and the incidence of RKFD and NOCKD. Subgroup analyses and optimization of predictive models were conducted based on baseline characteristics of participants. During follow-up, 402 RKFD and 220 NOCKD cases were documented. Higher eGDR was associated with reduced risk of RKFD (OR: 0.87, 95% CI: 0.81-0.94, p < 0.001) and NOCKD (OR: 0.88, 95% CI: 0.80-0.97, p = 0.01) per 1.0-SD increment. Restricted cubic splines models showed a linear relationship (non-linear p > 0.05), with increased RKFD/NOCKD risk when eGDR < 10.405 mg/kg/min. Adding eGDR improved predictive ability for RKFD (AUC: 0.659 vs. 0.672, p = 0.012) and NOCKD (AUC: 0.532 vs. 0.539, p = 0.004). This study demonstrated that lower eGDR levels in Chinese participants aged over 45 years without CKD are associated with an increased risk of developing RKFD and NOCKD.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disorder. Between 85% and 90% of cases result from variations in the PKD1 and PKD2 genes. Over 30 genes have been associated with ADPKD, contributing to its heterogeneity. This study aimed to investigate novel variations in the PKD1, PKD2, and ADPKD-related genes through whole-exome sequencing (WES) and combine the genotype and phenotype data of the patients. WES was performed on peripheral blood samples from 44 ADPKD patients, and variations were evaluated and classified based on ACMG criteria. A heterozygous pathogenic/likely pathogenic (P/LP) PKD1 variant was identified in 33 patients (75%). Seven patients had a heterozygous P/LP PKD2 variant (15.9%). No heterozygous P/LP PKD1 or PKD2 variant was found in 4 patients (9.1%), and one of them (2.3%) had a heterozygous pathogenic PKHD1 variant. Thirteen novel PKD1 variations were identified, with nine associated with fast estimated glomerular filtration rate (eGFR) decline. Potentially pathogenic Variants of Uncertain Significance in ALG9, CEP290, NPHP4, WDR19, and TTC21B were identified in three patients lacking PKD1/PKD2 variants. Survival analysis indicated that patients with PKD1 or PKD2 or without any PKD1/PKD2 mutations experienced a similar age of onset for end-stage kidney disease. The annual decline in eGFR was significantly higher in patients with a PKD1 mutation than in those with a PKD2 mutation, along with a higher Mayo Class. Genetic studies evaluating novel variants in the PKD1, PKD2, and ADPKD-related genes alongside patients' clinical data are essential for a deeper understanding of ADPKD diagnosis, prognosis, and pathology.

In recent years, artificial intelligence (AI) has advanced significantly in the field of pathomics, enabling the transformation of pathological images into high-throughput, machine-readable datasets for quantitative analysis and precise diagnosis in renal pathology. AI-based pathomics has introduced innovative perspectives and sophisticated tools for detecting glomerular injury, evaluating renal interstitial fibrosis, monitoring transplanted kidney pathology longitudinally, and predicting outcomes in renal tumors. Despite its great promise, the application of AI-based pathomics in nephrology still faces several challenges, including complex data annotation, limited model interpretability, lack of comprehensive multi-modal data integration, and insufficient large-scale clinical validation. Future research should prioritize these challenges by enhancing multi-omics integration and promoting interdisciplinary collaboration, thereby advancing AI-based pathomics in nephrology and ultimately improving the precision and efficiency of patient care.

Obstructive sleep apnea (OSA) has been widely associated with DN in observational studies; however, the causal nature and direction of this association remain uncertain. To clarify this, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using large-scale genetic datasets. Genetic instruments for OSA were derived from a genome-wide association study (GWAS) comprising up to 476,853 individuals, while genetic associations for DN were obtained from another GWAS including 452,280 participants. We applied multiple MR methods to ensure robust causal inference, including inverse variance weighting, MR-Egger regression, weighted median, weighted mode, and simple mode. Sensitivity analyses were thoroughly conducted using Cochran's Q test for heterogeneity and the MR-Egger intercept test to assess potential pleiotropy. Furthermore, multivariable MR was employed to evaluate the independent effect of OSA on DN after adjusting for hyperlipidemia and hypertension. The results indicated a significant causal effect of OSA on DN risk, supported by IVW (OR = 1.41, 95% CI: 1.12-1.77, p = 0.003) and weighted median estimates (OR = 1.57, 95% CI: 1.16-2.13, p = 0.003). Reverse MR analysis revealed no evidence of a causal effect of DN on OSA. Importantly, after accounting for hyperlipidemia and hypertension, multivariable MR confirmed that OSA exerts an independent causal influence on DN (OR = 0.90, 95% CI: 0.14-1.67, p = 0.021). These findings suggest that OSA may contribute to the pathogenesis of diabetic nephropathy through specific mechanisms, independent of traditional metabolic risk factors.

Avacopan, a novel C5a receptor inhibitor, offers therapeutic potential for ANCA-associated vasculitis. This study assessed its post-marketing safety using the FDA Adverse Event Reporting System (FAERS) from Q4 2021 to Q4 2024. Disproportionality analyses identified 75 adverse events (AEs) potentially linked to avacopan, with hepatobiliary disorders and infections being most prominent. A total of 62 AEs were classified as having moderate clinical priority, including drug-induced liver injury, renal failure, and deafness. Subgroup analysis revealed age- and sex-based differences in AE patterns. Logistic regression indicated that older age and concomitant use of rituximab or proton-pump inhibitors increased the risk of hepatobiliary AEs. These findings highlight the need for close monitoring of hepatic function and infection risk during avacopan therapy. Further research is warranted to explore the underlying mechanisms and potential drug interactions.

Biopsy-confirmed anticancer drug-induced kidney injury is underreported. This study aimed to characterize its clinicopathological features and outcomes. We retrospectively analyzed 52 patients with biopsy-proven anticancer drug-induced nephrotoxicity (2005-2024). Patients were classified into chemotherapy drugs (CTD, n = 25), molecularly targeted therapies (MTT, n = 22), and immune checkpoint inhibitors (ICI, n = 5; PD-1 inhibitors). The CTD group (e.g. cisplatin, capecitabine, gemcitabine) caused frequent acute kidney injury (AKI, 80%), with acute tubulointerstitial nephritis (ATIN, 32%). Notable glomerular lesions in the CTD group included thrombotic microangiopathy (TMA, 12%), minimal change disease (8%), and focal segmental glomerulosclerosis (8%). The MTT group (e.g. bevacizumab, lenvatinib, sorafenib) had higher proteinuria (0.4 vs. 3.1 vs. 0.7 g/24h; p < 0.05) and TMA incidence (86%). MTT-induced TMA produced distinct subtypes: anti-VEGF(R) therapy (n = 11) caused glomerular capillary ballooning (100%); non-VEGFR-TKIs (n = 4) were associated with segmental glomerulopathy; combined anti-VEGF/VEGFR-TKI (n = 4) resulted in more extensive and severe TMA (>75% of glomeruli). ICI therapy (nivolumab, camrelizumab, sintilimab) led to early AKI, mainly ATIN (80%), with glomerular IgA deposition (80%) and low serum C3 (60%). After a median follow-up of 23.0 months, MTT showed faster AKI recovery than CTD (0.5 vs. 8.0 months; p = 0.002). Anticancer drugs induce distinct nephrotoxic patterns. CTD causes direct cytotoxicity and high irreversible injury risk. MTT drives functional TMA, and new-onset hypertension with proteinuria should raise concern for anti-VEGF-related TMA. ICI triggers immune dysregulation with humoral disturbances, and AKI with low serum C3 can be a safety signal for clinical monitoring.

Diabetic kidney disease (DKD) remains a critical challenge in diabetes management, necessitating a deep understanding of its molecular underpinnings for better diagnosis and treatment strategies. This study was conducted to identify and validate novel biomarkers for DKD by integrating multi-omics analysis and experimental validation. Through weighted gene co-expression network analysis and Mendelian randomization analysis, 11 genes were identified as being causally associated with DKD. ADARB2, GOLPH3L, LRG1, and PEX6 were identified as characteristic genes through machine learning methods, including least absolute shrinkage and selection operator (LASSO) regression and SVM algorithms. Receiver operating characteristic curve analysis demonstrated that the characteristic genes had high predictive accuracy for DKD. Functional enrichment analyses indicated that dysregulation of key genes was associated with inflammatory and immune responses in both peripheral blood mononuclear cells and kidney single-cell populations. Peripheral blood samples from DKD patients and healthy controls were collected to assess the reliability of identified key genes in humans. Kidneys from wild-type and db/db mice were harvested to further validate the reliability of key genes at the tissue level in animal models using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). After RT-qPCR validation, the robustness of LRG1 and PEX6 was confirmed in both human peripheral blood and mouse kidney tissues. The significance of ADARB2 was confirmed in the kidney tissue of DKD mouse models. This study highlights the power of multi-omics analyses in elucidating complex disease pathogenesis and identifying biomarkers, thereby laying a foundation for the development of DKD-targeted therapeutics.