Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study.

AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

Worldwide burden and trends of diabetes among people aged 70 years and older, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Diabetes places a significant burden on personal and public health. However, a comprehensive assessment of the burden of diabetes in older adults is lacking. We aimed to estimate the global burden of diabetes and explore trends for the population aged ≥70 from 1990 to 2019. METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the prevalence, mortality, and disability-adjusted life-years (DALYs) of diabetes among people aged ≥70 were estimated by sex and age group in 2019. We also assessed the epidemiological trend of diabetes from 1990 to 2019. RESULTS: In 2019, 110.1 million (95% uncertainty interval [UI]: 101.2-119.4) people aged ≥70 years were living with diabetes (types 1 and 2 combined) with a global prevalence of 23.7% (21.8%-25.8%). Worldwide, 181.9 deaths (163.0-194.7) per 100,000 population and 4512.3 DALYs (3861.3-5264.2) per 100,000 population occurred due to diabetes. In 2019, minor sex-related disparities in the burden of diabetes were identified among specific age and sex groups. From 1990 to 2019, the prevalence of diabetes increased by 39.7% (37.7%-41.7%), and the related mortality and DALY rates also increased (16.4% [9.43%-22.9%] and 22.3% [17.2%-27.0%], respectively). CONCLUSION AND RELEVANCE: The global burden of diabetes in adults aged ≥70 has increased markedly from 1990 to 2019. As the population continues to age, there is an urgent need to combat the increasing disease burden.

Crescents proportions above 10% are associated with unfavorable kidney outcomes in IgA nephropathy patients with partial crescent formation.

PURPOSE: Whether different crescentic proportions determine the progression of IgA nephropathy (IgAN) with crescents in less than 50% of glomeruli remains controversial. We aimed to evaluate the relationship between different proportions of crescents and kidney outcomes in IgAN with partial crescent formation. METHODS: Patients diagnosed as IgAN, having at least two crescents and in less than 50% of glomeruli, were categorized into three groups: Group I (crescents in ≤10% of glomeruli), Group II (10%< crescents ≤25% of glomeruli) and Group III (crescents >25% of glomeruli). Baseline clinicopathological parameters were evaluated. The kidney endpoint was a composite of a ≥ 40% decline in the initial estimated glomerular filtration rate, end-stage kidney disease, and kidney disease-related death. RESULTS: Of 183 IgAN patients with crescents in less than 50% of glomeruli, baseline 24-hour urinary protein and immunosuppressive treatment varied among the three groups (p < 0.05). During a median follow-up of 57 months (interquartile range 28-86), 50 (27.3%) patients reached the composite outcome. Kaplan-Meier survival analysis revealed that kidney survival in Group II (p = 0.049) and Group III (p = 0.008) was significantly shorter than in Group I, with no significant difference between Group II and III (p = 0.2). After adjusting for clinical factors and MEST score based on the multivariate Cox regression analysis, a crescent proportion >10% (HR = 3.431, 95% CI 1.067-11.03, p = 0.039) was predictive of time to unfavorable kidney outcome, with model adjustments improving predictability (c-index: 0.817). CONCLUSION: The proportion of crescents reaching 10% of glomeruli in IgAN was identified as an independent risk factor for kidney survival.

Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy.

Objectives: Converging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investigated the correlation between glomerular C3 deposits and RPS DN classification and the combined deleterious effects thereof on kidney function. Methods: The study analyzed data from 217 diabetic patients who underwent renal biopsy between 2010 and 2021 and were found to have DN as the only glomerular disease. C3 deposition was considered positive if the glomerular C3 immunofluorescence intensity was at the trace or ≥1+ level. We divided DN into five glomerular lesion classes and separately evaluated the degree of interstitial and vascular involvement. The primary outcome was the composite of a ≥50% decline from the initial estimated glomerular filtration rate, end-stage renal disease, and death. Results: None of the patients were classified into class I, and few were classified into classes IIa (7.8%) and IV (9.2%). Most patients were classified as IIb (30.9%) and III (52.1%). C3 deposition was detected in 53.9% of patients. Multivariate logistic regression analysis showed that DN class was significantly correlated with C3 deposits [odds ratio, 1.59; 95% confidence interval (CI), 1.08-2.36; p = 0.02). During a median follow-up of 22 months, 123 (56.7%) patients reached the composite outcome. The endpoints occurred more frequently in patients with C3 deposition (69.2 vs. 42%) compared with those without C3 deposition. Patients with C3 deposition in either class IIb [hazards ratio (HR), 3.9 (95% CI, 1.14-13.17) vs. 2.46 (95% CI, 0.68-8.89)] or III [HR, 4.98 (95% CI, 1.53-16.23) vs. 2.63 (95% CI, 0.77-9.0)] had a higher risk of adverse kidney outcomes than those without C3 deposition. The prognostic accuracy of the combination of DN class and C3 deposits at 1 and 3 years was higher than that for DN class only. Conclusions: Complement deposition together with DN class predicts more rapid deterioration of kidney function in DN, which underlines the clinical significance of the DN phenotype according to the RPS classification.

Expression of LXR­ß, ABCA1 and ABCG1 in human triple­negative breast cancer tissues.

Previous studies have reported that liver X receptor (LXR), ATP­binding cassette sub­family G number 1 (ABCG1) and ATP­binding cassette transporter number 1 (ABCA1), which are associated with cholesterol metabolism, may be associated with the development and progression of breast cancer. The expression levels of LXR­ß, ABCA1 and ABCG1 in triple­negative breast cancer (TNBC) tissues and in non­cancerous mammary tissues were observed by immunohistochemistry, quantum dot­based immunohistochemistry, western blot analysis and reverse transcription­quantitative polymerase chain reaction. The present study identified that the expression of ABCA1 in TNBC tissues was higher than that in non­cancerous mammary tissues. A high expression of ABCA1 in the TNBC tissues was significantly associated with the histological grade. However, no significant differences were identified between the expression levels of LXR­ß and ABCG1 in the TNBC tissues compared with the non­cancerous mammary tissues. Therefore, the findings of this study suggest that ABCA1 is a specific marker for TNBC.

Clinical Significance of Gli-1 And Caveolin-1 Expression in the Human Small Cell Lung Cancer

Background: Lung cancer is the leading causes of cancer-related deaths around the world. Abnormal activation of the hedgehog (Hh) signaling pathway has been found to be involved in the occurrence, invasion, and metastasis of cancers. Autophagy also plays a significant role in the growth and metastasis of cancers. However, the correlation between the Hh signaling pathway and autophagy in small cell lung cancer (SCLC) is still poorly understood. This study aimed to investigate the significance of Hh signaling pathway and autophagy in SCLC. Materials and Methods: The expression of the Hh-induced transcriptional factor, glioma associated oncogene-1 (Gli-1) and the autophagy-related molecule caveolin-1 (Cav-1) and their clinical significance was performed to detect and assay by immunohistochemistry in tissue microarray including 70 patients with SCLC. Results: In our study, 47 (67.1%) patients had positive Gli-1 expression, 49 (70.0%) patients had positive Cav-1 expression, and 44 (62.9%) patients had negative fibroblastic Cav-1 expression. In SCLC, Gli-1 expression increased markedly, and was closely associated with decreased fibroblastic Cav-1 expression. Furthermore, we also found that Gli-1 expression was closely associated with increased Cav-1 expression. Conclusions: Our findings suggested that abnormal activation of the Hh signaling pathway is closely related to autophagy in SCLC. We envision that novel targets may come with the further investigation of Gli-1 and Cav-1 in carcinogenesis of SCLC.

Role of Glioma-associated GLI1 Oncogene in Carcinogenesis and Cancertargeted Therapy.

Glioma-associated oncogenes (GLIs) are zinc finger protein family members and downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI proteins influence the growth and development of organisms and aid in tissue repair. However, aberrant expression of the GLI family member GLI1 promotes carcinogenesis by inducing epithelial-mesenchymal transition (EMT), angiogenesis, and other signaling pathways. Overexpression of GLI1 is thought to be an indicator of poor prognosis as well as a potential therapeutic target for cancers. GLI inhibitors such as zerumbone, GANT61, resveratrol, and cyclopamine depress the Hh pathway in vitro and in vivo cancer research, and other non-canonical pathways may also activate expression of GLI1. Here, we summarize GLI function in carcinogenesis and cancer-targeted therapy.