Crescentic IgA nephropathy (IgAN), defined as .50% crescentic glomeruli on kidney biopsy, is one of the most common causes of rapidly progressive GN. However, few studies have characterized this condition. To identify risk factors and develop a prediction model, we assessed data from patients$14 years old with crescentic IgAN who were followed $12 months. The discovery cohort comprised 52 patients from one kidney center, and the validation cohort comprised 61 patients from multiple centers. At biopsy, the mean serum creatinine (SCr) level 6 SD was 4.363.4 mg/dl, and the mean percentage of crescents was 66.4%615.8%. The kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%64.7%, 45.8%65.1%, and 30.4%66.6%, respectively. Multivariate Cox regression revealed initial SCr as the only independent risk factor for ESRD (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.10 to 1.57; P=0.002). Notably, the percentage of crescents did not associate independently with ESRD. Logistic regression showed that the risk of ESRD at 1 year after biopsy increased rapidly at SCr.2.7 mg/dl and reached 90% at SCr.6.8 mg/dl (specificity=98.5%, sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr.6.8 mg/dl were less likely to recover from dialysis. Analyses in additional cohorts revealed a similar association between initial SCr and ESRD in patients with antiglomerular basement membrane disease but not ANCA-associated systemic vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr concentration may predict kidney failure in patients with this disease.

BackgroundThe coexistence of IgA nephropathy (IgAN) and antineutrophil cytoplasmic autoantibodies (ANCAs) is relatively rare. Only a few studies have reported the features of these patients.MethodsWe studied the clinical and histological features of 20 ANCA-positive IgAN patients. They were compared with ANCA-negative IgAN patients (n = 40) and ANCA-associated systemic vasculitis (AASV) patients (n = 40) with a randomly selected and matched proportion of crescentic glomeruli. Furthermore, 9 ANCA-positive crescentic IgAN patients out of the 20 cases were compared with two control groups with crescentic nephritis.ResultsANCA-positive IgAN patients showed older age, lower haemoglobin and higher inflammatory indicator levels at baseline, and a higher percentage of general symptoms and pulmonary involvement, compared with ANCA-negative IgAN patients, and were comparable to AASV patients. Histologically, there was a significantly higher percentage of fibrinoid necrosis in glomeruli in ANCA-positive IgAN patients and in AASV patients compared with ANCA-negative IgAN patients (35, 25 and 0%, respectively, P = 0.003). After immunosuppressive therapy, ANCA-positive crescentic IgAN patients were more likely to withdraw from dialysis (75 versus 9.1%, P = 0.03) and not to reach end-stage renal disease within 6 months (11.1 versus 66.7%, P = 0.01) compared with ANCA-negative crescentic IgAN patients.ConclusionsIgAN patients with ANCA positivity showed more severe clinical and histological features when compared with ANCA-negative IgAN patients and were comparable to AASV patients. However, renal prognosis was relatively better in ANCA-positive crescentic IgAN patients after aggressive immunosuppressive therapy in the short term, compared with ANCA-negative patients.

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Aldo-keto reductase 1B10 (AKR1B10) has relatively specific lipid substrates including carbonyls, retinal and farnesal/geranylgeranial. Metabolizing these lipid substrates appears crucial to carcinogenesis, particularly for farnesal/geranylgeranial that involves in protein prenylation. Mutant Kras is a most common active oncogene in pancreatic cancer, and its activation requires protein prenylation. To directly determine the role of AKR1B10 in pancreatic carcinogenesis, we knocked down AKR1B10 in CD18 human pancreatic carcinoma cells using shRNA approach. Silencing AKR1B10 resulted in a significant inhibition of anchor-dependent growth (knockdown cells vs vector-control cells: 67 ± 9.5 colonies/HPF vs 170 ± 3.7 colonies/HPF, P < 0.01), invasion index (0.27 vs. 1.00, p<0.05), and cell migration (at 16 hours 9.2 ± 1.2% vs 14.0 ± 1.8%, at 24 hours 21.0 ± 1.1% vs 30.5 ± 3.5%, and at 48 hours 51.9 ± 5.7% vs 88.9 ± 3.0%, P < 0.01). Inhibition of AKR1B10 by oleanolic acid (OA) showed a dose-dependent inhibition of cell growth with IC50 at 30µM. Kras pull-down and Western blot analysis revealed a significant down-regulation of active form Kras and phosphorylated C-Raf, and Erk, as well as an up-regulation of E-cadherin. A significant reduction of in vivo tumor growth was observed in nude mice implanted the CD18 pancreatic carcinoma cells with AKR1B10 knockdown (tumor weight: 0.25 ± 0.06g vs. 0.52 ± 0.07g, P = 0.01), and with OA treatment (tumor weight: 0.35 ± 0.05g vs. 0.52 ± 0.07g, P = 0.05). Our findings indicate AKR1B10 is a unique enzyme involved in pancreatic carcinogenesis via modulation of Kras-E-Cadherin pathway.

ObjectivesObesity is associated with cardiovascular diseases and has become the main public health issue in western countries and urban China. However, the prevalence and secular trends of obesity in rural China are currently unknown. The aim of this study was to investigate secular trends in the prevalence of overweight and obesity among rural adults in northern China between 1991 and 2011.MethodThe prevalence of overweight and obesity was assessed in adults aged 35–74 years living in a rural area in northern China by comparing two surveys that were conducted in 1991 and 2011, respectively.ResultThe age-adjusted prevalence of overweight increased from 24.5% in 1991 to 42.0% in 2011, and the prevalence of obesity increased from 5.7% in 1991 to 19.6% in 2011. Over the 21-year period, there were significant increases in the prevalence of overweight and obesity for both men and women in all age groups; however, the greatest increase was observed in men aged 35–44 years, with an 10.3-fold increase in obesity prevalence. The prevalence of obesity increased significantly in all risk factors categories, including education levels, blood pressure categories, diabetes previous history, current smoking situation and alcohol drinking situation over the past 21 years overall (p<0.05). The greatest increase in obesity prevalence appeared among those who consumed alcohol (increased by 8.0-fold). Next, there was a 5.3-fold increase in the prevalence of obesity in illiterate residents.ConclusionThe prevalence of overweight and obesity has increased rapidly among rural adults in Tianjin over the past 21 years, with the most dramatic increase observed in young men. Therefore, the burden of obesity should serve as a call for action.