The activated mesangial cell is an important therapeutic target for the control of glomerulonephritis. The peroxisome proliferator-activated receptor α (PPARα) has attracted considerable attention for its anti-inflammatory effects; however, its roles in the mesangial cells remain unknown. To determine the anti-inflammatory function of PPARα in mesangial cells, wild-type and Ppara-null cultured mesangial cells were exposed to lipopolysaccharide (LPS). LPS treatment caused enhanced proinflammatory responses in the Ppara-null cells compared with wild-type cells, as revealed by the induction of interleukin-6, enhanced cell proliferation, and the activation of the nuclear factor (NF)-κB signaling pathway. In wild-type cells resistant to inflammation, constitutive expression of PPARα was undetectable. However, LPS treatment induced the significant appearance and substantial activation of PPARα, which would attenuate the proinflammatory responses through its antagonizing effects on the NF-κB signaling pathway. The induction of PPARα was coincident with the appearance of α-smooth muscle actin, which might be associated with the phenotypic changes of mesangial cells. Moreover, another examination using LPS-injected wild-type mice demonstrated the appearance of PPARα-positive cells in glomeruli, suggesting in vivo correlation with PPARα induction. These results suggest that PPARα plays crucial roles in the attenuation of inflammatory response in activated mesangial cells. PPARα might be a novel therapeutic target against glomerular diseases.

Objective: To assess through systematic review and meta-analysis whether plasma exchange (PE) is associated with prognosis in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. Methods: A systematic search of PubMed, MEDLINE, Embase, and CENTRAL databases from inception to 17 June 2020 was conducted. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. Randomised controlled trials (RCTs) comparing PE vs. non-PE in AAV patients (microscopic polyangiitis [MPA], granulomatosis with polyangiitis [GPA], or eosinophilic granulomatosis with polyangiitis [EGPA]) were included. The combined risk ratio (RR) was calculated by the random-effects model using the Mantel-Haenszel method. Heterogeneity was measured using the I² statistic. Primary outcomes were mortality, clinical remission (CR), and adverse events (AEs). Results: Four RCTs comparing PE vs. no PE (N = 827) and 1 RCT comparing PE vs. pulse steroid treatment (N = 137) were included. All participants were MPA or GPA patients (no EGPA patients). PE was not associated with main primary outcomes compared with no PE (mortality RR 0.93 [95% confidence interval {CI} 0.70–1.24], I² = 0%; CR RR 1.02 [95% CI 0.91–1.15], I² = 0%; and AE RR 1.10 [95% CI 0.73–1.68], I² = 37%) or pulse steroid (mortality RR 0.99 [95% CI 0.71–1.37]; CR [the Birmingham Vasculitis Activity score] mean difference − 0.53 [95% CI − 1.40–0.34]; and AE RR 1.05 [95% CI 0.74–1.48]). Focusing on the early treatment phases, PE was associated with a reduction in end-stage renal disease incidence compared with both no PE (PE 1/43 vs. no PE 10/41; RR 0.14 [0.03–0.77] at 3 months) and pulse steroid (PE 11/70 vs. pulse steroid 23/67; RR 0.46 [0.24–0.86] at 3 months). Conclusion: We carried out a systematic review and meta-analysis targeting all AAV patients, including MPA, GPA, and EGPA. In AAV patients, performing PE was not associated with the risk of mortality, CR, and AE. No RCT exists evaluating the efficacy of PE for EGPA; hence, this is required in the future. The results may affect the development of guidelines for AAV and may indicate the direction of future clinical research on AAV. Trial registration: UMIN R000045239, PROSPERO CRD42020182566.

Cell-free and concentrated ascites reinfusion therapy (CART) is frequently used to treat refractory ascites in Japan. However, its efficacy remains unclear. This controlled cohort study verified the serum albumin elevating effect of CART by comparisons with simple paracentesis. Ascites patients receiving CART (N = 88) or paracentesis (N = 108) at our hospital were assessed for the primary outcome of change in serum albumin level within 3 days before and after treatment. A significantly larger volume of ascites was drained in the CART group. The change in serum albumin level was +0.08 ± 0.25 g/dL in the CART group and −0.10 ± 0.30 g/dL in the paracentesis group (P < 0.001). The CART – paracentesis difference was +0.26 g/dL (95%CI +0.18 to +0.33, P < 0.001) after adjusting for potential confounders by multivariate analysis. The adjusted difference increased with drainage volume. In the CART group, serum total protein, dietary intake, and urine volume were significantly increased, while hemoglobin and body weight was significantly decreased, versus paracentesis. More frequent adverse events, particularly fever, were recorded for CART, although the period until re-drainage was significantly longer. This study is the first demonstrating that CART can significantly increase serum albumin level as compared with simple paracentesis. CART represents a useful strategy to manage patients requiring ascites drainage.

As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease.

Purpose: A high flow access (HFA) may cause heart failure in patients with an arteriovenous fistula (AVF) undergoing hemodialysis (HD) and is associated with poor prognosis. There are a variety of blood flow suppression techniques for treating HFA; however, the therapeutic outcome is still unclear. Methods: The following three different blood flow suppression methods were performed on 74 patients with HFA: proximal artery banding with distal artery ligation (A-ban with A-lig: 12 cases); shunt vein banding (V-ban: 37 cases); and anastoplasty (Ana: 25 cases). Results: There were no differences in the sex or mean age or duration of HD between the treatment groups. The A-ban with A-lig method was mainly selected for patients with a distal AVF and the anastoplasty method was selected most often for patients with a cubital AVF. The techniques were equally effective in reducing flow volume (FV) and the FV/cardiac output ratio (Flow/CO) to target levels, and clinical symptoms improved in all patients. The rates of HFA recurrence and AVF occlusion were significantly higher in the V-ban group (18.9% and 24.3%, respectively). A small proportion of patients in each treatment group developed a postoperative infection. Conclusions: Each method proved to be an effective means of treating HFA. The choice of surgical method should be informed by the type of vascular access; however, the A-ban with A-lig and Ana methods appear to achieve clinically significant reductions in FV and have lower rates of HFA recurrence and AVF occlusion.