It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn’t been elucidated. This study was therefore conducted to assess the association between M2 and peritoneal fibrosis related to PD. In this study, peritoneal fibrosis was induced by intraperitoneal (i.p.) injection of Lactate-4.25% dialysate (100 mL/kg) to C57BL/6J mice for 28 days, and liposome-encapsulated clodronate (LC, the specific scavenger of macrophages) was used to treat the peritoneal fibrosis mice model by i.p. injection at day 18 and day 21. All animals were sacrificed at day 29. Parietal peritonea were stained with Masson’s trichrome, and the expression of type I collagen (Col-I), fibronectin, mannose receptor (CD206), transforming growth factor beta (TGF-β), chemokine receptor 7 (CCR7), chitinase 3-like 3 (Ym-1) and arginase-1 (Arg-1) was determined by Western blotting, immunofluorescence and quantitative real-time PCR. Our results revealed that peritoneal thickness, Col-I, fibronectin, CD206, TGF-β, Ym-1 and Arg-1 were upregulated in the peritoneal fibrosis mice model, and all of these indexes were downregulated in those treated with LC. Additionally, there was no difference in the level of CCR7 between the model and treatment group. Our study indicated that peritoneal M2 played an important role in the process of peritoneal fibrosis related to PD and might be a potential target for intervention therapy of peritoneal fibrosis.

Background/Aims: The aim of the study was to investigate clinicopathological characteristics, the role of immunosuppressive therapy and renal outcome in IgA nephropathy (IgAN) patients with hyperuricemia. Methods: 206 biopsy-proven primary IgAN patients were included between January 2010 and December 2015, and divided into two groups: patients without hyperuricemia (n=122), and patients with hyperuricemia (n=84). The clinicopathological features, response, renal outcome and safety were recorded. In univariate and multivariate models, hyperuricemia-associated pathological factors were analyzed. Results: The patients with hyperuricemia presented higher systolic blood pressure, worse kidney function and more severe time-averaged proteinuria. Proportions of glomerulosclerosis, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, lymphocytes and monocytes infiltration were higher, while the proportion of segmental adhesion was lower in patients with hyperuricemia. By multivariate logistic regression analysis, only tubular atrophy/interstitial fibrosis (T1∼2) (HR=3.969, 95% CI=1.439−10.945, P=0.008) was significantly associated with hyperuricemia. For hyperuricemic patients, the response rate to therapy and renal survival rate were significantly higher in patients that received RAS blockade in combination with immunosuppressive therapy. After RAS blockade treatment, renal survival in the patients with hyperuricemia was worse compared with the patients without hyperuricemia. Conclusion: Hyperuricemic IgAN patients presented more severe clinical features. Tubulointerstitial injury could be a pathological feature closely related to hyperuricemia in IgAN. Immunosuppressive therapy and RAS blockade could reduce proteinuria and improve renal outcome in IgAN patients with hyperuricemia.

Background: Dyslipidemia is common in chronic kidney disease (CKD), including immunoglobulin A (IgA) nephropathy (IgAN), and may be associated with renal prognosis; however, the value of dyslipidemia in IgAN remains insufficiently assessed. The objective of our study was to investigate clinicopathological characteristics and renal outcomes in IgAN patients with dyslipidemia and to evaluate the prognostic value of lipid abnormalities. Methods: This cohort study included 458 primary IgAN patients for a retrospective analysis. The clinicopathological features and renal outcomes were recorded. In univariate and multivariate models, the associations between dyslipidemia and renal outcomes, as well as dyslipidemia-associated pathological features, were analyzed. Results: Patients with dyslipidemia—defined as a total cholesterol of ≥5.2 mmol/L, triglycerides of ≥1.7 mmol/L, or low-density lipoprotein cholesterol [LDL-C] of ≥3.4 mmol/L—exhibited elevated complement levels and worse clinical characteristics with regard to blood pressure, proteinuria, kidney function, and glomerulosclerosis; tubular atrophy/interstitial fibrosis (T1–2), crescents, and vascular lesions were more common. A multivariate logistic regression revealed that T1–2 and arterial intimal fibrosis were significantly associated with dyslipidemia. After a mean follow-up of 54.7 months, dyslipidemia ( p = 0.001), especially abnormalities in total cholesterol ( p = 0.016) and triglycerides ( p = 0.001), was significantly associated with poorer renal survival, and renal survival was not improved after lipid-lowering therapies. In addition to estimated glomerular filtration rate (eGFR) and arterial intimal fibrosis, dyslipidemia is an independent predictor for renal survival in multivariate Cox analyses (model 1: HR, 2.206; 95% CI, 1.127–4.317; p = 0.021; model 2: HR, 2.085; 95% CI, 1.059–4.106; p = 0.034). Conclusion: IgAN patients with dyslipidemia exhibited more severe clinicopathological features. Tubular atrophy/interstitial fibrosis and arteriosclerosis/arteriolosclerosis were closely associated with dyslipidemia. Dyslipidemia not only indicates adverse renal outcomes but also serves as an independent prognostic predictor.