Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well‐established murine model with progressive renal disease. MR images were acquired from 16‐week‐old fibrotic hHB‐EGFTg/Tg mice and normal wild‐type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two‐pool five‐parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB‐EGFTg/Tg mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB‐EGFTg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.

OBJECTIVEOxidative stress is a major contributing factor in the development of diabetic nephropathy. Peroxisome proliferator–activated receptor γ heterozygous mice and Pro12Ala polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Pro12Ala polymorphism, alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 760 Chinese patients with type 2 diabetes.RESEARCH DESIGN AND METHODSAmong patients, 532 had diabetic nephropathy with microalbuminuria (n = 245) or overt albuminuria (n = 287), and 228 did not show either of these symptoms but had had diabetes for ≥10 years and were not undergoing antihypertension treatment.RESULTSAfter adjustment for confounders, the Pro/Pro genotype was significantly associated with diabetic nephropathy (odds ratio 2.30 [95% CI 1.18–4.45], P = 0.014); smoking was also an independent risk factor for diabetic nephropathy (1.99 [1.08–3.68], P = 0.029). In addition, we identified possible synergistic effects; i.e., the high-risk group (smokers with the Pro/Pro genotype) showed 4.52 times higher risk (1.78–11.48, P = 0.002) of diabetic nephropathy than the low-risk group (nonsmokers with the Pro/Ala genotype) in a multiple logistic regression analysis controlled for the confounders.CONCLUSIONSOur results indicated that the Pro/Pro genotype and smoking were significant independent risk factors for diabetic nephropathy. The possible synergistic effects of genotype and smoking may aggravate oxidative stress and contribute to the development of diabetic nephropathy.

Background/Aims: Both the Acute physiology and Chronic Health Evaluation (APACHE II) score and mean platelet volume/platelet count Ratio (MPR) can independently predict adverse outcomes in critically ill patients. This study was aimed to investigate whether the combination of them could have a better performance in predicting prognosis of patients with acute kidney injury (AKI) who received continuous renal replacement therapy (CRRT). Methods: Two hundred twenty-three patients with AKI who underwent CRRT between January 2009 and December 2014 in a Chinese university hospital were enrolled. They were divided into survivals group and non-survivals group based on the situation at discharge. Receiver Operating Characteristic (ROC) curve was used for MPR and APACHE II score, and to determine the optimal cut-off value of MPR for in-hospital mortality. Factors associated with mortality were identified by univariate and multivariate logistic regression analysis. Results: The mean age of the patients was 61.4 years, and the overall in-hospital mortality was 48.4%. Acute cardiorenal syndrome (ACRS) was the most common cause of AKI. The optimal cut-off value of MPR for mortality was 0.099 with an area under the ROC curve (AUC) of 0.636. The AUC increased to 0.851 with the addition of the APACHE II score. The mortality of patients with of MPR > 0.099 was 56.4%, which was significantly higher than that of the control group with of ≤ 0.099 (39.6%, P= 0.012). Logistic regression analysis showed that average number of organ failure (OR = 2.372), APACHE II score (OR = 1.187), age (OR = 1.028) and vasopressors administration (OR = 38.130) were significantly associated with poor prognosis. Conclusion: Severity of illness was significantly associated with prognosis of patients with AKI. The combination of MPR and APACHE II score may be helpful in predicting the short-term outcome of AKI.

Although coronary artery recanalization after myocardial infarction improves patient outcomes, inadequate ventricular remodeling following ischemia-reperfusion (IR) injury and secondary cardiac fibrosis (CF) are common and can lead to heart failure. MicroRNAs (miRNAs) play an important role in cardiovascular disorders. However, the underlying molecular mechanism of miRNAs in the occurrence and progression of CF has not been fully elucidated. Herein, through the construction of an I/R rat model and an angiotensin II-induced CF cell model, we evaluated the role of miR-375-3p in the progression of CF. In the I/R rat model and CF cell model, miR-375-3p promoted fibrosis by accelerating the ferroptosis of cardiomyocytes through mediating glutathione peroxidase 4 (GPX4). Furthermore, we treated the rats or cell model with miR-375-3p antagomir (or inhibitor) and ferroptosis inhibitor Ferrostatin-1 (Fer-1). The results showed that miR-375-3p antagomir (or inhibitor) and Fer-1 promoted the antioxidant capacity of cardiac fibroblasts, reduced GPX4-mediated ferroptosis process and alleviated I/R-induced CF. In conclusion, this study revealed that miR-375-3p directly targeted GPX4—an inhibitor of the ferroptosis pathway. Meanwhile, miR-375-3p can be a new potential biomarker for the prevention and treatment of CF.