The tyrosine kinase inhibitor imatinib is beneficial in experimental renal diseases, but the effect of the new tyrosine kinase inhibitor nilotinib on the progression of renal failure is unknown. We administered either nilotinib or vehicle to Sprague-Dawley rats beginning 2 weeks after 5/6 nephrectomy (Nx) or laparotomy and continuing for 8 weeks. Serum creatinine levels were significantly lower in the nilotinib group after 6 and 8 weeks of treatment. Furthermore, nilotinib-treated rats had less proteinuria, attenuated glomerulosclerosis and tubulointerstitial damage, and reduced macrophage infiltration into the tubulointerstitium. Treatment with nilotinib also significantly decreased renal cortical expression of profibrogenic genes, such as IL-1␤ and monocyte chemotactic protein-1, which correlated closely with the tubulointerstitial damage score and ED1-positive macrophages score. In addition, nilotinib treatment significantly prolonged survival. Taken together, these results suggest that nilotinib may limit the progression of chronic kidney disease.

BACKGROUND It is well established that the pathogenesis of diabetic nephropathy is associated with abnormalities of renal nitric oxide (NO) generation. Many of the biological actions of NO are mediated by cGMP, which is rapidly degraded by phosphodiesterases. In this study, we evaluated the renoprotective effects of sildenafil (SIL), an inhibitor of phosphodiesterase‐5, in type 2 diabetic rats. METHODS Male Otsuka Long‐Evans Tokushima Fatty (OLETF) rats, a non‐insulin‐dependent diabetes model, and Long‐Evans Tokushima Otsuka rats, a non‐diabetic control, were treated with either SIL (2.5 mg·kg−1 in drinking water) or undosed water for 28 weeks, starting at 30 weeks of age. RESULTS Sildenafil treatment significantly decreased albuminuria, attenuated glomerular hyperfiltration and resulted in a decrease in glomerular hypertrophy, in addition to a reduced glomerulosclerosis score and a dramatic decrease in the number of glomerular and tubulointerstitial proliferating cell nuclear antigen‐positive cells in OLETF rats. This was accompanied by a significant reduction in renal cortical mRNA levels of collagen types I and III. The increased mRNA levels of matrix metalloproteinase (MMP)‐2, MMP‐9, tissue inhibitors of MMPs (TIMP)‐1 and TIMP‐2 in the OLETF rats were significantly or partially attenuated by SIL treatment. CONCLUSIONS This study suggests that SIL attenuated diabetic nephropathy due to its potent antiproliferative effects and its regulatory effects on extracellular matrix. This latter effect is thought to be a result of its ability to affect the balance between MMPs and their inhibitors.

No abstract

Background and objectives: The present study assesses the effects of the oxidative stress marker, myeloperoxidase (MPO), and the possible MPO-related oxidative stress marker, oxidative ␣ 1 -antitrypsin (oxAT), on carotid intima-media thickness (CIMT) and protein-energy wasting (PEW) in patients on hemodialysis (HD).Design, setting, participants, & measurements: Blood samples were obtained from 383 patients before HD to measure WBC count, serum albumin, lipids, high-sensitivity C-reactive protein (CRP), ␣ 1 -antitrypsin (AT), interleukin-6, oxidative LDL-C, MPO, and oxAT. We assessed both CIMT and the geriatric nutritional risk index (GNRI) in this cross-sectional competitive study.Results: Levels of MPO and oxAT correlated. Myeloperoxidase was associated with max-CIMT, and oxAT correlated with max-CIMT and GNRI. Multivariate linear regression models showed that MPO and oxAT were independent predictors of increasing max-CIMT, whereas oxAT, but not MPO, independently correlated with GNRI. In four combined MPO and oxAT groups classified according to median values, a multinomial logistic regression model showed that high MPO together with high oxAT was independently associated with increased max-CIMT. Moreover, the OR for max-CIMT with positive PEW and high MPO was significantly increased in the four groups with combined MPO and PEW.Conclusions: High MPO with high oxAT and high MPO with PEW seem to contribute to plaque formation in patients on HD, whereas elevated MPO or oxAT alone might not predict increasing CIMT. In contrast, a high oxAT value seems to be an independent predictor of PEW in patients on HD.

With the elastic belt, miscalculation of the pancreatic stiffness was reduced. MRE showed differences of stiffness between normal pancreas and pancreatic lesions.