Genyang Cheng

Clinical and prognostic implications of serum uric acid levels on IgA nephropathy: a cohort study of 348 cases with a mean 5-year follow-up.

AIM To assess the prognostic implications of serum uric acid levels on patients with IgA nephropathy in a longitudinal 8-year follow-up study and to identify an association between serum uric acid levels and the clinical and pathological phenotypes of IgA nephropathy. SUBJECTS AND METHODS We reviewed the files of all consecutive patients with IgA nephropathy treated at our hospital between 2001 and 2009. Analyses were performed to investigate the association between the level of serum uric acid and both clinical and pathological phenotypes of IgA nephropathy. Prognosis was assessed based on follow-up data. RESULTS At the same glomerular filtration rate (GFR), there was no significant difference in the levels of 24 hours proteinuria, blood urea nitrogen (BUN), and serum creatinine between the two groups with different levels of serum uric acid (p > 0.05). The prevalence of glomerular sclerosis as well as the scores of tubulointerstitial and vascular injury was greater in patients with high serum uric acid levels compared to patients with normal levels of serum uric acid (p < 0.05). At the end of the follow-up period, patients with high serum uric acid levels had a higher prevalence of reduced GFR and end stage renal disease (ESRD) than those with normal serum uric acid levels (40.82 vs. 15.70% and 64.71 vs. 35.00%, respectively; p < 0.05). CONCLUSIONS The serum uric acid level in patients with IgA nephropathy affects the pathophysiology and prognosis of the disease. We also identified a correlation between hyperuricemia and a higher risk of renal end points.

MiRNA-29c regulates the expression of inflammatory cytokines in diabetic nephropathy by targeting tristetraprolin

Diabetic nephropathy is one of the most prevalent chronic complications of Diabetes mellitus, but its pathogenesis remains elusive. This study was designed to determine the role of tristetraprolin (TTP), inflammatory cytokines and microRNAs (miRNAs) in DN. The blood and urine samples were obtained from 32 patients with DN, 33 patients with type 2 DM, and 35 normal healthy subjects as controls. Renal tissue samples were also obtained from 10 DN patients and 10 normal controls. The miRNA microarray analyses were performed in pooled plasma and urine sediment samples of eight DN patients and eight age- and sex-matched health control subjects and three paired renal tissues from patients with DN and normal controls. Conditionally immortalized mouse podocytes (MPC5) were used a cell model. The expressions of TTP and cytokines in patient samples and cultured cells were determined by qRT-PCR and Western blotting or ELISA. Our results indicated that miRNA-29c directly targeted TTP and promoted inflammatory response under hyperglycemic conditions. Overexpression of miRNA-29c in podocytes resulted in an increase in inflammatory cytokines and inhibition of miRNA-29c by using its inhibitor reduced the inflammatory cytokines in podocytes. Finally, miRNA-29c promoted the progression of DN by targeting TTP, providing a target for a therapeutic intervention of DN.

IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through the JAK2/STAT3 signaling pathway

Long-term peritoneal dialysis (PD) therapy results in functional and structural alteration of the peritoneal membrane, including epithelial-to-mesenchymal transition (EMT). Interleukin 6 (IL-6) is a local pleiotropic cytokine, hypothesized to play an important role in EMT. This study was designed to investigate the role of IL-6 in EMT and peritoneal membrane dysfunction in long-term PD patients by assessing the level of IL-6 in dialysate and exploring the relationship between IL-6, the related signaling pathway JAK2/STAT3, and EMT, using in vitro cellular and molecular techniques. Plasma and dialysate levels of IL-6 were significantly higher in PD ultrafiltration failure patients compared with patients without ultrafiltration failure and were negatively correlated with measures of PD adequacy. In vitro IL-6 treatment changed human peritoneal mesothelial cell phenotype from a typical cobblestone-like to a fibroblast-like appearance and increased cell viability. IL-6 treatment increased α-smooth muscle actin and vascular endothelial growth factor expression but decreased E-cadherin expression. IL-6 treatment activated the JAK/STAT signaling pathway. However, the JAK2/STAT3 inhibitor WP1066 prevented IL-6-induced activation of the JAK2/STAT3 pathway and EMT. We conclude that IL-6 promotes the EMT process, possibly by activating the JAK2/STAT3 signaling pathway. IL-6 may serve as a novel therapeutic target for preventing EMT, and preservation of the peritoneal membrane may arise from these studies.

Endothelin-receptor antagonist can reduce blood pressure in patients with hypertension: a meta-analysis

Abstract The aim of this meta-analysis was to assess the effectiveness and safety of endothelin-receptor antagonist (ERA) in the patients with hypertension. Searches of the PubMed, EMBASE, and CENTRAL databases were conducted to include all the randomized control trials (RCTs). Eighteen trials including 4898 patients were used in the meta-analysis, of which nine were classified as low risk of bias and the other nine as unclear risk of bias. There was no statistically significant difference in all-cause mortality between ERA and placebo groups [6 trials, fixed effects model, RR 1.53 (0.89–2.62); random effects model, RR 1.45 (0.84–2.52)]. ERA significantly reduced 24-h ambulatory blood pressure and sitting blood pressure in patients with hypertension [5 trials, 24-h SBP: WMD −7.65 (−8.95 to −6.36), 24-h DBP: WMD −5.92 (−7.50 to −4.33); 18 trials, SBP: WMD −6.12 (−7.87 to −4.36), DBP: WMD −3.81 (−4.82 to −2.80)]. However, ERA had more adverse events [within 24 h: 3 trials, RR 1.16 (0.82–1.65); after 24 h, 13 trials, RR 1.21 (1.08–1.36)] and severe adverse events than placebo controls [SAE: 9 trials, RR 1.34 (1.13–1.60)]. In addition, there is a potential need for further RCTs that focus on the use of ERA in patients with hypertension.

Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy

The current standard treatment for IgA nephropathy relies on steroid and/or immunosuppressive therapy and angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB). This study examines the benefits and safety of combining valsartan with clopidogrel and leflunomide as a treatment for progressive IgA nephropathy.

Author Correction: MiRNA-29c regulates the expression of inflammatory cytokines in diabetic nephropathy by targeting tristetraprolin

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Microarray analysis reveals long non‑coding RNA SOX2OT as a novel candidate regulator in diabetic nephropathy

Diabetic nephropathy (DN) is a highly complex syndrome involving multiple dysregulated biological processes. Long non-coding RNAs (lncRNAs) are now believed to have an important function in various diseases. However, their roles in DN remain largely unknown. Therefore, the present study was performed in order to investigate the lncRNAs that have a crucial role in DN. db/db mice were used as a DN model while db/m mice served as a control to search for lncRNAs which may have important roles in DN. Microarray and bioinformatics analysis gave an overview of the features of differentially expressed genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis demonstrated the typical biological alterations in DN. A co-expression network of lncRNAs and mRNAs revealed the complex interaction pattern in DN conditions. Further data investigation indicated that SOX2-overlapping transcript (SOX2OT), which was significantly downregulated in DN mice, may be the potentially functional lncRNA contributing to the onset of DN. The UCSC database demonstrated that SOX2OT was highly conserved in mice and humans. Additionally further study using cultured human podocytes and mesangial cells confirmed the downregulation of SOX2OT using reverse transcription-quantitative polymerase chain reaction and fluorescence in situ hybridization. However, the cellular location of SOX2OT depended on certain cell types. Taken together, the results of the present study indicated that SOX2OT may act as an important regulator in the pathogenesis of DN by interacting with various mRNAs with critical roles in DN.

miR-15a-5p suppresses inflammation and fibrosis of peritoneal mesothelial cells induced by peritoneal dialysis via targeting VEGFA: SHANG et al.

Long‐term peritoneal dialysis (PD) often ends up with ultrafiltration failure (UFF) which is partially caused by persistent inflammation and fibrosis of peritoneal tissues. However, the mechanism is still unclear. In the current study, the peritoneum from UFF patients demonstrated inflammation and fibrosis which were positively related to the expression of vascular endothelial growth factor A (VEGFA). The in vitro model using human peritoneal mesothelial cells (HPMCs) stimulated by high glucose or advanced glycation end (AGE) product showed consistent changes of inflammation, fibrosis, and VEGFA. Whats more, we showed that VEGFA was an instigator of inflammation and fibrosis. Several microRNAs (miRNAs) have been reported to regulate expression of VEGFA elsewhere. Five of them were selected to test the expression in the peritoneum of patients with PD. Results suggested that miR‐15a‐5p was the most significantly downregulated one. Also, in high glucose or AGE product‐stimulated HPMCs, miR‐15a‐5p decreased. When miRNA mimic was used to restore the expression of miR‐15a‐5p, high glucose‐induced VEGFA was repressed. The predicted binding site between these two molecules was confirmed by the dual‐luciferase assay. Restoration of miR‐15a‐5p restrained inflammation and fibrosis of HPMCs. TGF‐β1/Smad2 was shown to be the downstream signaling pathway and their activity was regulated by miR‐15a‐5p/VEGFA. In conclusion, our current study demonstrates that miR‐15a‐5p acts as a regulator of VEGFA mRNA and the following inflammation and fibrosis in peritoneal mesothelial cells. The miR‐15a‐5p/VEGFA pathway may be a potential target for preventing ultrafiltration failure in patients with PD.

Independent Association between Hyperuricemia and Histopathological Parameters in Chinese Patients with Henöch-Schönlein Purpura Nephritis

BACKGROUND This study aimed to investigate the role of hyperuricemia in the development of histopathological changes in HSPN. METHODS Clinical and laboratory data pertaining to 139 adult HSPN patients with and without elevated serum uric acid levels were retrospectively evaluated. There was a 14.4% prevalence of hyperuricemia in patients with HSPN. RESULTS Patients with hyperuricemia had higher levels of cystatin C and urine β2-microglobulin and lower levels of HDL-C in comparison to that in patients with normal serum uric acid levels (p < 0.05). Patients with hyperuricemia had higher scores of interstitial inflammation, tubular atrophy, interstitial fibrosis, glomerulosclerosis as compared to those normouricemic patients (p < 0.05). Serum uric acid was found to be correlated independently with the presence of interstitial inflammation, tubular atrophy, interstitial fibrosis, and glomerulosclerosis by multivariate analysis (p < 0.05). CONCLUSIONS High serum uric acid may be independently correlated with the development of tubulointerstitial lesions as well as glomerulosclerosis in HSPN.