Clinicopathological characteristics and prognosis in patients with monoclonal gammopathy and renal damage in central China: a multicenter retrospective cohort study.

Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.

Baicalin Reduces Renal Inflammation in Mesangial Proliferative Glomerulonephritis through Activation of Nrf2/ARE and PI3K/AKT Pathways.

OBJECTIVE: Mesangial proliferative glomerulonephritis (MPGN) is a prevalent form of primary glomerulonephritis, distinguished by the proliferation of mesangial cells and the accompanying inflammatory response. Baicalin, the active ingredient in the Scutellaria baicalensis Georgi plant, has been observed to have a protective effect on the kidneys. However, its specific impact on MPGN has yet to be studied widely. Hence, this study aimed to investigate the effect on MPGN and the underlying mechanisms of Baicalin. METHODS: Thirty-six Sprague-Dawley (SD) rats, aged 6 to 8 weeks, were randomly allocated into different subgroups: control, model, benazepril, and three baicalin subgroups (low, medium, and high dose), each consisting of six rats. The concentrations of 24-hour urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), triglycerides (TG), total cholesterol (TC), interleukins (IL-1α, IL-2, IL-10), and interferon-γ (IFN-γ) were measured with biochemistry. The pathological alterations in the renal tissue were examined using Hematoxylin and Eosin (HE) along with Periodic Acid-Schiff (PAS) staining. Concurrently, the extent of apoptosis was evaluated using TdT-mediated dUTP nick end labeling (TUNEL) staining. In vitro, mesangial cells were exposed to 30 µg/mL lipopolysaccharide for 24 h, with or without varying concentrations of baicalin (10, 20, 40 µM). MTT assay was applied to estimate cell activity, flow cytometry to evaluate the cell cycle, and 5-ethynyl-2-deoxyuridine (EdU) detection to measure cell proliferation. IL-1α, IL-2, IL-10, and IFN-γ concentrations in the cell supernatant were assayed with biochemistry. Furthermore, the expression of apoptosis-related proteins, concluding BCL2-Associated X (Bax), Bcl-2, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1, NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway-related proteins (Nrf2 and HO-1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway-related proteins (p-PI3K, PI3K, p-AKT, and AKT) in both the renal tissue and cell supernatant were measured. RESULTS: Baicalin treatment significantly reduced the 24-hour urinary protein, serum levels of BUN, SCr, TG, TC, IL-1α, IL-2, IL-10, and IFN-γ in vivo experiments. Baicalin treatment also improved the pathological condition of renal tissue and decreased the occurrence of apoptosis. In vitro, findings confirmed that baicalin inhabits the proliferation of mesangial cells triggered by Lipopolysaccharide (LPS), induces a G1 phase cell cycle arrest, and reduces the concentrations of IL-1α, IL-2, IL-10, and IFN-γ. Baicalin also decreased the ratios of p-PI3K/PI3K and p-AKT/AKT while enhancing the levels of Nrf2 and HO-1 in both renal tissue and cell supernatant. CONCLUSIONS: Baicalin can mitigate MPGN by impeding the proliferation and inflammation of mesangial cells by activating Nrf2/ARE and PI3K/AKT pathways.

The Survival and Complication Rates of Laparoscopic Versus Open Catheter Placement in Peritoneal Dialysis Patients: A Meta-Analysis.

The objective of this meta-analysis was to compare the outcomes of laparoscopic insertion method with a conventional open surgery. A systematical search was conducted in PubMed, Embase, and the Cochrane Library up to June 2014. Relative risks (RRs) and their 95% confidence intervals (CIs) were used as estimates. Four randomized-controlled trials and 10 cohort studies involving 2323 patients were identified. The pooled results showed that laparoscopic insertion technique significantly prolonged the 1-year survival (RR=1.23; 95% CI, 1.12-1.35) and 2-year survival (RR=1.36; 95% CI, 1.16-1.60). Meanwhile, laparoscopic insertion significantly decreased the probability of surgical intervention or catheter revision (RR=0.32; 95% CI, 0.15-0.69) and risk of migration (RR=0.31; 95% CI, 0.18-0.53) and obstruction (RR=0.43; 95% CI, 0.28-0.66). Thus, laparoscopic catheter placement may be superior to open surgery in peritoneal dialysis catheter placement.

Novel mechanism for mesenchymal stem cells in attenuating peritoneal adhesion: accumulating in the lung and secreting tumor necrosis factor α-stimulating gene-6.

INTRODUCTION: We previously found that mesenchymal stem cells (MSCs) injected intravenously could attenuate peritoneal adhesion by secreting tumor necrosis alpha-stimulating gene (TSG)-6, while MSCs injected intraperitoneally could not. However, the underlying mechanism remains unclear. This study was designed to investigate the means by which MSCs exert their effects. METHODS: Rat bone marrow-derived MSCs/red fluorescent protein (RFP) were injected either intraperitoneally or intravenously into Sprague-Dawley (SD) rats at different time points after peritoneal scraping. Peritoneal adhesions were evaluated macroscopically at day 14 after scraping. The distribution of MSCs injected intraperitoneally or intravenously was traced by two-photon fluorescence confocal imaging and immunofluorescence microscopy. The co-localization of MSCs and macrophages in the lung and the spleen, and the expression of TSG-6 in MSCs trapped in the lung or the spleen were evaluated by immunofluorescence microscopy. The concentration of TSG-6 in serum was evaluated by ELISA. After intravenous injection of TSG-6- small interfering (si) RNA-MSCs, the expression of TSG-6 in MSCs and the concentration of TSG-6 in serum were reevaluated, and peritoneal adhesions were evaluated macroscopically and histologically. RESULTS: MSCs injected intraperitoneally failed to reduce peritoneal adhesion, and MSCs injected intravenously markedly improved peritoneal adhesion. Two-photon fluorescence confocal imaging showed that MSCs injected intravenously accumulated mainly in the lung, where they remained for seven days, and immunofluorescence microscopy showed few MSCs phagocytosed by macrophages. In contrast, large numbers of MSCs accumulated in the spleen with obvious phagocytosis by macrophages even at 4 hours after intraperitoneal injection. Immunofluorescence microscopy showed that MSCs that accumulated in the lung after intravenous injection could express TSG-6 within 12 hours, but TSG-6-siRNA-MSCs or MSCs accumulated in the spleen after intraperitoneal injection did not. ELISA showed that the concentration of TSG-6 in serum was increased at 4 hours after intravenous injection of MSCs, while there was no increase after injection of TSG-6-siRNA-MSCs or after intraperitoneal injection of MSCs. Moreover, intravenous injection of TSG-6-siRNA-MSCs failed to attenuate peritoneal adhesion. CONCLUSIONS: Our findings suggest that intravenously injected MSCs accumulated in the lung and attenuated peritoneal adhesion by secreting TSG-6, but intraperitoneally injected MSCs were phagocytosed by macrophages in the spleen and failed to attenuate peritoneal adhesion.