Elevated plasma FXII is associated with disease activity in ANCA-associated vasculitis: A Retrospective Cross-Sectional Study in Western China.

This study examined whether plasma FXII levels reflect disease activity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Plasma FXII levels were detected by ELISA in 127 patients with AAV, and their associations with disease activity and plasma myeloperoxidase (MPO)-ANCA titre were examined. Immunofluorescent co-staining of FXII and neutrophils was performed on the renal tissues of patients with AAV. MPO expression in renal biopsy tissues was determined by immunohistochemical staining. The association between plasma FXII levels and histological activity was assessed in 82 patients who underwent kidney biopsy. Plasma FXII levels were considerably increased in patients with clinically active AAV compared to those in clinical remission and healthy individuals. Plasma FXII levels correlated positively with creatinine (r = 0.377), CRP (r = 0.222), urine red blood cell (r = 0.203), serum MPO-ANCA titer (r = 0.353), white blood cell (r = 0.194), percentage of glomeruli with crescents (P = 0.001), capillary breaks (P = 0.001), interstitial inflammation (P < 0.001) and fibrinoid necrosis (p < 0.001) on kidney biopsy. The plasma FXII optimal cut-off value for evaluating AAV activity was 24.5 µg/mL (sensitivity = 0.81, specificity = 0.82, P = 0.0001), which was superior to that achieved using conventional serologic biomarkers. Co-expression of FXII and neutrophils was higher, with increased MPO expression, in renal tissue with pathologically active AAV than that observed in pathologically inactive tissues. In conclusion, elevated plasma FXII levels reflect AAV clinical and histologic activity, and can serve as markers of active AAV.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

[Efficacy of hirudin in treating immunoglobulin A nephropathy with hematuria: a randomized controlled trial].

OBJECTIVE: To investigate the curative effects and side effects of hirudin in treating immunoglobulin A nephropathy (IgAN) with hematuria and minimal proteinuria in a short-term. METHODS: Two hundred and sixty-two histologically confirmed cases of IgAN with hematuria and minimal proteinuria from 1998 to 2007 were randomly divided into hirudin-treated group (peroral administration of Maixuekang capsules) and dipyridamole-treated group (peroral administration of dipyridamole). In the two groups, contrast analysis of conformation and counts of erythrocytes in urine, urine protein quantitation in 24 hours, levels of serum creatinine (Scr) and creatinine clearance rate (Ccr), blood lipid, five items of blood clotting and side effects was performed. RESULTS: After six-month treatment, the anisotrophy rate and the counts of erythrocytes in urine, and the urine protein quantitation in 24 hours in hirudin-treated group were decreased distinctly as compared with pre-treatment (P<0.01) and dipyridamole-treated group (P<0.05). On the other hand, Ccr was increased obviously in hirudin-treated group as compared with pre-treatment and dipyridamole-treated group (P<0.01). The blood lipid was also ameliorated in hirudin-treated group, but there was no significant difference. The anticoagulation effect of hirudin was better than dipyridamole (P<0.01). Efficacy assessment showed that the total response rate, complete remission rate and predominance remission rate in hirudin-treated group were higher than those in dipyridamole-treated group. Few side effects were found in both groups, and the rate of adverse reaction in gastrointestinal tract was lower in hirudin-treated group as compared with that in dipyridamole-treated group (P<0.05). CONCLUSION: Compared with dipyridamole, hirudin has superiority in kidney protection and decreasing the anisotrophy rate, counts of erythrocytes in urine and the urine protein.

[Effect of p21 on the changes in renal tubular epithelial cells after ischemia/reperfusion injury of kidney].

OBJECTIVE: To investigate the contribution of p21 gene in renal tubular epithelial cells in p21 (+/+) and p21 (-/-) mice of young and old ages at different times after kidney ischemia/reperfusion injury (IRI). METHODS: In p21 (+/+) and p21 (-/-) male mice at the ages of 2 and 12 months the kidneys were made ischemic by clamping the left renal artery for 45 minutes followed by declamping. On 0, 1, 3 and 7 days, 1, 3 and 6 months after reflow, renal tissue was processed for pathological study, determination of proliferating cell nuclear antigen (PCNA), apoptosis and senescence-associated beta-galactosidase (SA-beta-gal) analysis, using hematoxylin and eosin staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick-end labeling (TUNEL), and histochemical staining, respectively. RESULTS: Renal tubule necrosis and cell apoptosis were more severe in p21 (-/-) mice and old mice as compared with p21 (+/+) mice and young mice (both P<0.05), respectively. In young p21 (+/+) mice, occasionally faint staining for SA-beta-gal activity began to appear after 1 month, and significantly increased 3 and 6 months after IRI (P<0.05), but there was no positive staining for SA-beta-gal in the contralateral kidney or both kidneys in p21 (-/-) mice at any time. Another manner of the expression of SA-beta-gal was detected in aged p21 (+/+) mice, as both kidneys showed intensely positive staining for SA-beta-gal at 0 day after IRI, it then subsided notably on 1 day in the IRI kidney (P<0.05), but increased again at 3 months, though still less intense than the contralateral kidney, albeit more intense than the young mice at the same time (P<0.05). Three months after IRI, in both the IRI kidney and the contralateral kidney, positive staining for SA-beta-gal almost reached the same level. On the contrary, only occasional faint staining for SA-beta-gal activity was observed in aged p21 (-/-) mice at any time. No significant difference in positive staining of nuclear PCNA was found between in young and aged p21 (+/+) mice (P>0.05), although the numbers of positively stained nuclear PCNA were more in number in young mice than in aged mice. But in p21 (-/-) mice, significantly more cells were positively stained for PCNA, especially in young mice and in IRI kidneys (P<0.05). Correlation analysis between senescent and apoptotic cells in aged mice made at 1 day after IRI showed striking negative correlation between both of them [p21 (+/+) mice: r=-0.82; P<0.001; p21 (-/-) mice: r=-0.76, P<0.001]. CONCLUSION: IRI can promote the senescence process of normal tubular cells, and can accelerate death (necrosis and apoptosis) process of senescent tubular cells. p21 gene may play an important role in the senescence changes in tubular epithelial cells after kidney ischemia/reperfusion injury.

[Expression of monocyte chemoattractant protein-1 in glomerular endothelial cells stimulated by high concentration of glucose].

AIM: To study the expression of monocyte chemoattractant protein-1 (MCP-1) in cultured human glomerular endothelial cells (HUGECs) stimulated by high concentration of glucose. METHODS: The effect of high concentration of glucose on the expression of MCP-1mRNA by HUGECs was detected by in situ hybridization and cell ELISA. The monocyte migration induced by the conditioned media of cultured HUGECs was assayed by a modified Boyden Chamber micropore filtration membrane method. Effects of anti-MCP-1 antibody on monocyte migration was detected as well. RESULTS: The MCP-1 mRNA was only weakly expressed in HUGECs cultured under the condition of low concentration of glucose. Following a stimulation of high concentration of glucose (25 mmol/L), MCP-1 mRNA expression was upregulated from the 8th hour and reached the maximum at the 16th hour. Conditioned medium of cultured HUGECs stimulated with high concentration of glucose had marked chemotaxis for monocytes, which was inhibited by anti-MCP-1 antibody. CONCLUSION: HUGEC stimulated by high glucose may highly express MCP-1, and produce chemotatic factors for monocytes.