Xiaoxue Zhang

Comparison between adults and children with Henoch–Schönlein purpura nephritis

BackgroundHenoch–Schönlein purpura (HSP) mainly affects children, but age is also thought to be an important prognostic factor. Kidney involvement is a major cause of mortality in HSP patients. The purpose of this study was to analyze the clinicopathological correlations between adults and children.MethodsA total of 208 children and 75 adult patients with HSP nephritis (HSPN) were evaluated. All patients underwent a renal biopsy.ResultsExtra-renal symptoms (arthritis and abdominal pain) were more common in the pediatric patient group than in the adult group (P < 0.05), but renal symptoms (edema and hypertension) were relatively rare (P < 0.05). A significant positive correlation was noted between pathological type and clinical type (P < 0.01). Pathological activity was positively related to renal failure, abdominal pain, microscopic hematuria, hypertension, and proteinuria (P < 0.05). Pathological chronicity was positively associated with age, duration of follow-up since the onset of palpable purpura, renal failure, lower extremity edema, hypertension, and proteinuria (P < 0.05).ConclusionsVarious clinicopathological differences exist between children and adults with HSPN. Massive proteinuria, renal failure, and abdominal pain usually correlated with severe pathology. Renal biopsy should be performed in both pediatric and adult HSPN patients with repeated hematuria and/or consistent minimal proteinuria.

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.

Dose-Response Between Cardiovascular Risk Factors and Cardiovascular Mortality Among Incident Peritoneal Dialysis Patients.

Background/Aims: Traditional cardiovascular (CV) risk factors (RFs) and their management targets may not be applicable to specific medical subpopulations, particularly dialysis patients. This study aimed to evaluate the dose-response association between measurements of RFs, cardiovascular mortality, and potential metabolic targets among Chinese patients initializing peritoneal dialysis (PD). Methods: Risk-set sampling was applied to two population based 1: 10 case-control studies of incident PD patients, matched by age, sex and the year of initialisation of PD: a main sample (204 cases and 2,040 controls) and a replication sample (81 cases and 810 controls). The dose-response association between continuous measurements of CV RFs (blood pressure, fasting glucose, body mass index, total cholesterol, phosphate and ejection fraction) at baseline and the 2-year CV mortality were analyzed using conditional Logistic regression. The final threshold was chosen based upon a significant break in the regression coefficients and achievement of the minimum Bayesian information criterion (BIC). Results: A linear relationship was identified between fasting glucose and CV mortality. Non-linear associations between other measurements and CV mortality suggested potential metabolic treatment intensification thresholds as < 145/92mmHg for blood pressure, < 1.70mmol/L for phosphate, 24 kg/m2 for body mass index, 4.6mmol/L for total cholesterol, and > 60% for ejection fraction respectively. Conclusion: Our findings highlight the potential importance of more intensive glucose management, anti-hypertensive treatment and dietary management among PD patients. We recommend that the clinical relevance of these epidemiological associations be tested using randomized controlled trials of multifaceted interventions.

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.

Derivation and Validation of Risk Scores to Predict Cerebrovascular Mortality Among Incident Peritoneal Dialysis Patients

Background/Aims: Cerebrovascular disease (CeVD) is one of the leading causes of death in patients initialising peritoneal dialysis (PD). Currently there is no risk score to predict the future risk of CeVD on entry into PD. This study aimed to derive and validate a risk prediction model for CeVD mortality in 2 years after the initialisation of PD. Methods: All patients registered with the Henan Peritoneal Dialysis Registry (HPDR) between 2007 and 2014 were included. Multivariable logistic regression modelling was applied to derive the risk score. All accessible clinical measurements were screened as potential predictors. Internal validation through bootstrapping was applied to test the model performance. Results: The absolute risk of CeVD mortality was 2.9%. Systolic and diastolic blood pressure, total cholesterol, phosphate, and sodium concentrations were the strongest predictors of CeVD mortality in the final risk score. Good model discrimination with C statistics above 0.70 and calibration of agreed observed and predicted risks were identified in the model. Conclusion: The new risk score, developed and validated using clinical measurements that are accessible on entry into PD, could be used clinically to screen for patients at high risk of CeVD mortality. Such patients might benefit from therapies reducing the incidence of CeVD related events.

Inhibition of microRNA-182-5p contributes to attenuation of lupus nephritis via Foxo1 signaling

&NA; MiR‐182–5p suppresses expression of Foxo1 that is a protective factor in renal disorders and is up‐regulated in systemic lupus erythematosus patients. Thus, we hypothesized that dys‐function of miR‐182–5p/Foxo1 axis contributed to development of lupus nephritis (LN). Firstly, we investigated the expressions of miR‐182–5p and Foxo1 in LN patients and during growth of LN MRL/lpr mice. Then we subjected MRL/lpr mice to the injection of miR‐182–5p antagomirs and assessed the effect of miR‐182–5p inhibition on renal structure and function. In vitro, we administrated renal cell lines with TGF‐&bgr;1 to explore the relation between renal fibrosis and miR‐182–5p. The level of miR‐182–5p was up‐regulated in high Chronicity Index patients while the level of Foxo1 was suppressed. The progression of LN in mice was associated with the increased level of miR‐182–5p and the decreased level of Foxo1. The inhibition of miR‐182–5p ameliorated renal structure and function impairments associated with LN, along with the increased expression of Foxo1. The administration of TGF‐&bgr;1 in vitro increased the expression of miR‐182–5p in renal cells in an overall dose‐dependent manner. The current study demonstrated that the expression of miR‐182–5p was increased in LN patients, contributing to the suppression of Foxo1 and development of LN. HighlightsMiR‐182–5p is up‐regulated in LN patients.Foxo1 is down‐regulated in LN patients.MiR‐185–5p promotes development of LN by inhibiting Foxo1.Inhibition of miR‐182–5p attenuates LN symptoms.

The protective effect of mycophenolate mofetil on residual renal function in peritoneal dialysis patients: an open label feasibility study.

This study aims to evaluate the safety of mycophenolate mofetil (MMF) and its effect on residual renal function (RRF) during peritoneal dialysis (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.