Kidney Diseases最新文献

Introduction: Weight gain and central obesity are common in peritoneal dialysis (PD) patients. In the general population, body roundness index (BRI) has been found to be a convenient anthropometric measurement for the assessment of central obesity and visceral adiposity. However, the role of BRI in PD patients has not been explored.

Methods: We recruited 145 new PD patients. BRI, body composition by bioimpedance spectroscopy, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were measured at baseline and then after 1 year of PD. Patients were stratified into four groups based on their changes in BRI after 1 year of PD, using the traditional BRI cutoff of 5. Outcome measures include patient survival and hospitalization rate.

Results: The change in BRI after 1 year of PD had a modest but significant correlation with the change in HOMA-IR (r = 0.497, p = 0.041). For the group with baseline BRI <5, patients who had their BRI raised to ≥5 (low-high group, n = 20) had significantly lower patient and technique survival rates than those whose BRI remained <5 (low-low group, n = 55), and the result remained significant after adjusting for clinical confounders by multi-variable Cox regression (adjusted hazard ratio 2.885, 95% CI: 1.278-6.509, p = 0.011). The low-high group also had significantly higher hospitalization rates (2.51 [1.63-3.93] vs. 0.98 [0.26-1.91] per year, p = 0.0008) and longer hospitalization stay (17.3 [12.2-35.5] vs. 5.0 [1.0-13.3] days per year, p = 0.015) than the low-low group.

Conclusion: An increase in BRI after 1 year of PD was associated with worsening of insulin resistance, worse patient survival, and more hospitalization.

Introduction: The post-biopsy International IgA Nephropathy Prediction Tool (IIgAN-PT) models were updated to assess progression risk 1 or 2 years after biopsy. This study externally validated both models in a contemporary Asian cohort with extended follow-up to evaluate long-term predictive performance.

Methods: We included 1,296 Chinese patients with biopsy-proven IgAN. The primary outcome was a composite of end-stage kidney disease or a 50% decline in estimated glomerular filtration rate (eGFR) within 1 year post-biopsy. Model performance was evaluated using the coefficient of determination (R ²) and Akaike information criterion to assess model fit, concordance statistics (C-statistics) and Kaplan-Meier survival curves for discrimination, and the integrated calibration index (ICI) for calibration. Further analysis included net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis.

Results: Over a median follow-up of 4.5 years (IQR: 2.2-7.6), 20.2% of patients experienced the primary outcome. Models with and without race demonstrated excellent performance, with R ² of 81.0% and 80.2%. C-statistics for 4- and 5-year risk prediction were 0.89 and 0.87, respectively. Kaplan-Meier curves showed clear separation between risk strata, especially in the highest-risk group, who had lower baseline eGFR and a steeper decline. Calibration was good for both 4- and 5-year predictions as reflected by the ICI. Nonetheless, both models underestimated risk in the highest-risk group at these time points. Discrepancies became more apparent beyond 10 years, as confirmed by DCA. Compared to the original models, the updated models improved risk reclassification, as indicated by both NRI and IDI for 4- and 5-year risk prediction.

Conclusion: The post-biopsy IIgAN-PT models demonstrated good predictive performance and may support individualized risk stratification and treatment decisions in IgAN.

Introduction: Alpinia galanga (L.) rhizome has been widely consumed as a spice and food-flavoring agent and in traditional medicines for the treatment of various diseases such as stomach pain, vomiting, diarrhea, infections, and renal disorders. The clinical use of gentamicin (Genta), an aminoglycoside antibiotic, is constrained due to nephrotoxicity. The existing investigation intended to estimate the mechanistic antioxidant, anti-inflammatory, and anti-apoptotic actions of galangal essential oil (Gal EO) against nephrotoxicity induced by Genta.

Materials and methods: Gal EO was isolated and subjected to GC-MS for analysis. The oil components were in silico investigated against Genta-induced renal toxicity targets using network pharmacology and molecular docking approaches. In vivo studies involved the alienation of rats into four groups. The control and Genta groups rats received 0.5% CMC orally by gavage for 2 weeks and saline or Genta (100 mg/kg) I.P. injection on the 8th to the 14th day. The Genta + Gal EO (50 mg/kg) and Genta + Gal EO (100 mg/kg) groups received Gal EO (50 or 100 mg/kg, P.O.) daily for 2 weeks and Genta (100 mg/kg) I.P. injection. Renal histopathological and kidney function tests, lipid peroxidation, oxidative, inflammatory mediators, and apoptotic markers were assessed.

Results: Network Pharmacology suggested Toll-like receptors 4 (TLR4) and interleukin-1beta (IL-1β) as potential targets of Gal EO components in Genta-induced renal toxicity. Gal EO significantly decreased Cr, uric acid, BUN, CysC, NGAL, and Kim-1 levels and the urine albumin/creatinine ratio. Gal EO reduced MDA and NO levels with an upsurge in the GSH content, GPx, GSH-R, catalase, and SOD levels. Gal EO lessened the gene expression of TLR4/MYD88/NF-κB/IL-1β with subsequent reduction in ICAM-1 and MCP-1 expression and the levels of MPO, TNF-α, and IL-6 while intensified IL-10. Gal EO diminished caspase 3, caspase 9, and Bax while amplified Bcl2.

Conclusion: Genta-induced nephrotoxicity was mitigated by the anti-inflammatory, antioxidant, and anti-apoptotic effect of Gal EO through decreasing TLR4/MYD88/NF-κB/IL-1β signaling pathway.

Background: Although the World Health Organization no longer classifies coronavirus disease 2019 (COVID-19) as a global health emergency, its long-term sequelae continue to affect survivors physically, psychologically, and socially.

Summary: This review focuses on a vulnerable population - patients receiving kidney replacement therapy (KRT) - and summarizes their COVID-19-associated epidemiological characteristics, clinical manifestations, clinical outcomes, interventions, and vaccination challenges.

Key messages: KRT patients faced markedly higher severe acute respiratory syndrome coronavirus 2 infection risks, atypical clinical presentations, and high mortality rates. Specialized management strategies for patients on KRT were recommended. COVID-19 vaccination formed the cornerstone of controlling COVID-19 but also raised concerns over its long-term safety and immunogenicity profiles.

Objective: Diabetic nephropathy (DN), a critical complication of diabetes, is characterized by progressive renal function impairment and fibrosis development. F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin ligase, is recognized for its role in metabolic disorders; however, its specific functions and mechanisms in DN remain incompletely understood. This study aimed to clarify the role of FBXW7 in the pathogenesis of DN.

Methods: Mouse tubular epithelial cells (mTECs) cultured under hyperglycemic conditions were used. FBXW7 overexpression was induced in the kidneys of db/db mice and in mTECs to evaluate its effects on renal fibrosis and related molecular pathways. The interaction between FBXW7 and metadherin (Mtdh) was examined by using co-immunoprecipitation and Western blotting techniques.

Results: FBXW7 expression was found to be significant reduced in the kidneys of DN patients and db/db mice. Overexpression of FBXW7 markedly improved albuminuria, blood urea nitrogen, uric acid levels, and renal fibrosis in db/db mice. Additionally, FBXW7 was shown to inhibit high glucose-induced fibrosis in mTECs through a mechanism involving the ubiquitin-mediated degradation of Mtdh, a protein known to promote fibrosis. Suppression of Mtdh via FBXW7 overexpression was also linked to inactivation of TGF-β/Smad3 signaling in DN.

Conclusion: These findings highlight the protective role of FBXW7 in DN by downregulating Mtdh and indicate that FBXW7 represents a promising therapeutic target for DN.

Introduction: Diabetic nephropathy (DN) is a major cause of end-stage renal disease, characterized by podocyte injury and impaired autophagy. Epitranscriptomic mechanisms, particularly N6-methyladenosine (m6A) RNA modifications, have emerged as critical regulators in kidney disease, but their role in autophagy regulation within podocytes remains poorly understood. The aim of this study was to investigate the role of the m6A demethylase FTO in regulating podocyte autophagy and the pathogenesis of diabetic kidney disease (DKD), with a focus on its downstream effector ATF3.

Methods: The study employed a multitiered approach involving human kidney biopsies from DN patients, in vitro podocyte models under high-glucose conditions, and podocyte-specific FTO knockout (iPFKO) mice. Key assessments included m6A immunoprecipitation sequencing to identify m6A-modified transcripts, RNA stability assays, Western blotting, immunofluorescence, transmission electron microscopy, and histological analysis. Autophagy flux was evaluated using LC3-II/LC3-I ratios and p62 accumulation.

Results: FTO was selectively upregulated in podocytes from human DN samples and high-glucose-treated cells. FTO overexpression led to global m6A hypomethylation, especially affecting autophagy-related transcripts. ATF3 was identified as a hypomethylated, stabilized transcript whose expression was enhanced by FTO. Elevated ATF3 suppressed transcription of autophagy genes (e.g., LC3, ULK1, ATG5, Beclin1), impairing autophagy flux. FTO knockdown or ATF3 inhibition restored autophagy in vitro. In iPFKO mice, FTO deletion reduced ATF3 expression, preserved autophagy, and attenuated proteinuria, glomerular damage, and foot process effacement under diabetic conditions.

Conclusions: FTO impairs podocyte autophagy in DKD via m6A demethylation-mediated stabilization of ATF3. Targeting the FTO-ATF3 axis may offer a promising therapeutic strategy to preserve podocyte integrity and mitigate DKD progression.

Introduction: This study aimed to evaluate the guideline concordance of chronic kidney disease (CKD) testing among high-risk patients in a city in Northwest China and identify key factors influencing testing practices.

Methods: A retrospective cohort study was conducted using electronic health records data across Weinan city. The study included 202,847 adult patients diagnosed with diabetes and/or hypertension, excluding those with known CKD at baseline. Considering albuminuria test is not available in Weinan city, guideline-concordant CKD testing in this study was defined as conducting annual tests for both estimated glomerular filtration rate (eGFR) and proteinuria throughout the follow-up period, with the endpoint being the incidence of CKD or mortality. A Cox regression model was used to identify key factors influencing CKD testing practices.

Results: The study population had 19.3% diagnosed with diabetes only, 71.8% with hypertension only, and 8.9% with both conditions. Throughout the follow-up period, only 0.70% of participants underwent annual tests for both eGFR and proteinuria as recommended by guidelines, while 3.44% had at least one test for both eGFR and proteinuria. Better adherence to CKD testing guidelines was associated with presence of diabetes, male gender, younger age, higher educational attainment, nonsmoking status, urban healthcare insurance, residence in urban areas, and engagement in light physical work.

Conclusion: Routine CKD testing in Northwest Chinese with diabetes and hypertension remains uncommon, despite guideline recommendations. Given that diabetes and hypertension are leading causes of CKD in China, these findings emphasize the urgent need for strategies to improve kidney health management among high-risk populations.

Background: Crescentic lupus nephritis (cLN) is an uncommon and severe phenotype in LN with limited data on outcomes and relevant risk factors.

Methods: Eighty-three cases of biopsy-proven LN with ≥50% crescents were included. Another 83 non-crescentic LN patients with <50% crescents (non-cLN) were matched through propensity score as the control group.

Results: The cLN patients accounted for 4.03% of LN patients in renal biopsy. Compared with age- and gender-matched non-cLN patients, cLN patients had higher serum creatinine levels, anti-neutrophil cytoplasmic antibody (ANCA) positivity rates, activity index, and chronic index scores, while the positive rate of anti-dsDNA antibodies and complement 3 were lower. The cLN patients exhibited a lower treatment response rate than matched non-cLN patients (34.8% vs. 64.3%, p < 0.001). The median follow-up period was 87.97 (interquartile range: 19.5-181.4) months, and cLN patients had a lower renal survival rate. The 5 years renal survival rate of cLN and matched non-cLN patients were 30.6%, 77.2%, respectively (p < 0.001). There was no significant difference in overall survival rate between the two groups (p = 0.375). Wire-loop lesions and renal tubular atrophy >50% were identified as risk factors for ESRD in cLN patients. Elevated serum creatinine level at baseline was a risk factor for death in cLN patients.

Conclusions: cLN patients had worse treatment response and renal outcomes than non-cLN but the mortality risk was similar. The presence of wire-loop lesions and renal tubular atrophy >50% on renal biopsy may predict ESRD in cLN patients.

Background: Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria and presenting microscopically as focal segmental sclerosis of the glomerulus, often progresses to end-stage renal disease. Patients with primary FSGS who undergo kidney transplantation often experience recurrence, leading to graft function loss and ultimately a shortened life span. However, the pathogenesis about post-transplant recurrence of FSGS remains unclear.

Summary: The mainstream hypothesis is the circulating factor, which mediates podocyte injury. Although a unified gold standard circulating factor has yet to be established, several candidate circulating factors have been proposed, including soluble urokinase plasminogen activator receptor (suPAR), the CD40-CD40L axis, cardiotrophin-like cytokine factor 1 (CLCF-1), apolipoprotein A-Ib (ApoA-Ib), and anti-nephrin antibody. These candidates have demonstrated associations with recurrent FSGS in clinical or basic research, but each has certain limitations. Additionally, advancements in renal biopsy, podocyte molecular signaling targets, and microRNAs provide support for the development of novel molecular biomarkers. Currently, there is no unified guideline for the treatment of post-transplant recurrent FSGS. Common therapeutic options include plasma exchange, calcineurin inhibitors, corticosteroids, and rituximab.

Key messages: This article summarizes the latest research advancements of circulating factors in post-transplant recurrence of FSGS and also highlights recent discoveries in potential molecular biomarkers and therapeutic approaches. Post-transplant recurrence of FSGS is a rare and complex heterogeneous disease that seriously affects the health of patients. The review aimed to provide valuable and up-to-date information support for researchers in this field and give potential research perspectives in the future.

Introduction: The growing threat of chronic kidney disease (CKD) to human health has gained considerable attention. But a comprehensive analysis of the CKD burden in China at both the national and provincial level has not been done. This study aimed to investigate the CKD burden by age, gender, CKD causes, and geographical region in China from 1990 to 2021.

Methods: We studied the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of CKD, its risk factors, and associated diseases both at the national and provincial level by analyzing data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Average annual percentage changes (AAPCs) calculated from joinpoint model were used to estimate the temporal trends from 1990 to 2021. Decomposition analysis was employed to quantify the contributions of population growth, aging, and epidemiological changes to CKD burden. Bayesian age-period-cohort model was utilized to forecast the disease burden up to 2050.

Results: In 2021, China had 118.40 million cases of CKD, including 3.32 million incident cases, resulting in 0.20 million deaths. We found a clear upward trend in the age-standardized incidence rate of CKD from 1990 to 2021 (AAPC = 0.32%/year, 95% CI: 0.29-0.35). Substantial disparities in CKD burden were observed across sexes, age-groups, and provinces, with older adults and residents of middle/low-middle sociodemographic index (SDI) provinces experiencing a higher burden. Furthermore, it is projected that more people will develop CKD in the next 3 decades, with hypertension and type 2 diabetes emerging as predominant causes. A decomposition analysis further indicated that population aging serves as the primary contributor to the rising CKD burden. High fasting plasma glucose, high blood pressure, and high body-mass index were among the top three risk factors for CKD. Moreover, impaired kidney function contributed to 8.18 million cardiovascular diseases DALYs, 6.13 million CKD DALYs, and 0.04 million gout DALYs. CKD is a severe health concern in China.

Conclusion: To alleviate the disease burden, effective prevention and intervention strategies tailored to local conditions are necessary, particularly targeting high-risk populations and provinces with middle and low-middle SDI.