Purpose. Hirudin, a polypeptide structure containing 65 amino acids, is a potent natural thrombin inhibitor with anticoagulant property extracted from Hirudo medicinalis. It has been reported to have anti-inflammatory and antifibrotic property. Here we explored the renoprotective effect of hirudin on unilateral ureteral obstruction (UUO) induced renal interstitial fibrosis (RIF). Methods. Rats were randomly divided into five groups: sham group, UUO alone group, and three UUO + hirudin-treatment groups (10, 20, or 40 IU/kg/d, for 14 continuous days). At the end of the experiment period, animals were sacrificed. Pathologic changes in renal specimens were observed using hematoxylin and eosin (HE) staining and Masson staining. The expressions of collagen III (Col III), fibronectin (FN), α-smooth muscle actin (α-SMA), protease-activated receptor 1 (PAR-1), and proteins in the TGF-β1/Smad and NF-κB pathways in renal tissues were examined by immunohistochemistry and/or Western blotting. Results. HE and Masson staining showed that hirudin-treated UUO rats had lower extent of renal injury and deposition of extracellular matrix (ECM) in renal interstitium than those in the UUO group. The results of immunohistochemistry and WB indicated decreased protein expressions of Col III, FN, α-SMA, PAR-1, and inflammatory markers such as tumor necrosis factor-α and interleukin-6 after hirudin treatment. Furthermore, hirudin reduced the expressions of transforming growth factor β1 (TGF-β1), phosphorylated-Smad2, and phosphorylated-Smad3 in the UUO model. In parallel, we found inhibited nuclear factor-κB (NF-κB) signaling after hirudin treatment, with downregulated protein expressions of P65, phosphorylated-P65, and phosphorylated-iκBα and increased iκBα. Conclusion. Hirudin improves kidney injury and suppresses inflammatory response and ECM accumulation in UUO rats; its underlying mechanism may be associated with the inhibition of TGF-β1/Smad and NF-κB signaling.
Background/Aims: Mounting clinical experience and evidence from scale observational studies have suggested that polycystic kidney disease (PKD) was not a contraindication for peritoneal dialysis (PD). Recent studies have reported that PD may be associated with a better prognosis in PKD than that of non-PKD patients. To solve the problem, we performed a systematic review and comprehensive meta-analysis to compare the outcomes between PKD and non-PKD patients on PD and the all-cause mortality between patients with PKD on PD and hemodialysis (HD). Methods: We conducted a systematic literature using electronic databases (PubMed, Ovid, Embase and Web of Science) to identify the studies reporting the endpoint events of PKD/non-PKD patients with PD and the all-cause mortality between patients with PKD on PD and HD, such as dialysis adequacy, technique failure, PD-related complications, the mode of RRT change, and all-cause mortality. We searched the literature published February 2018 or earlier. We used both fix-effects and random-effects models to calculate the overall effect estimate. A sensitivity analysis and subgroup analysis were performed to find the origin of heterogeneity. Results: 12 studies with a total of 17,040 patients reported the endpoint events of PKD/non-PKD patients with PD. No significant difference was observed on dialysis adequacy (Kt/V, SMD: -0.02, 95%CI: -0.12–0.08; D: Pcr (4h), SMD: -0.10, 95% CI: -0.26–0.06), technique failure (RR: 0.97, 95%CI: 0.78-1.20), RRT change (RR: 0.96, 95%CI: 0.77-1.19), total PD-associated complications (RR: 1.0, 95%CI: 0.91-1.09) and all-cause mortality (RR: 0.40, 95%CI: 0.33–0.47) in PKD patients, compared with non-PKD subjects undergoing PD. However, the proportion of renal transplantation in PKD patients was higher than that of non-PKD patients (RR: 2.04, 95%CI: 1.88–2.20) with significant heterogeneity (I2 =82.7%, P=0.000). 4 studies with a total of 5,762 patients reported that the all-cause mortality did not differ between the PKD patients on PD and HD (RR: 0.87, 95%CI: 0.72-1.06). Conclusion: Our meta-analysis found that the outcomes of given population of PKD patients on PD were at least not inferior as compared to those with other primary kidney diseases, and suggested that PKD might be not absolutely a contraindication for PD. Given the limitations of the proposed, it needs further large-scale studies to assess whether PD is a suitable RRT option for end-stage renal disease (ESRD) patients with PKD.
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