Serum Bilirubin Is Correlated With the Progression of IgA Vasculitis With Nephritis.

Background: Bilirubin has been identified as an endogenous antioxidant and cellular protectant. The present study was performed to clarify the potential influence of serum bilirubin on IgA vasculitis with nephritis (IgAV-N). Methods: One hundred and eighty-nine IgAV-N patients over 14 years old were enrolled. The patients were divided into two groups by the optimum cut-off value calculated by ROC curve. The composite endpoints were defined as a 60% decline in estimate glomerular filtration rate (e-GFR), end-stage renal disease (ESRD) and/or death. Kaplan-Meier (K-M) analysis and multivariate Cox analysis were carried out to determine the predictors for renal outcomes. In order to eliminate the influence of different baseline data, a 1:2 propensity score (PS) match was performed to make the results comparable and convictive. Results: The baseline data suggested that patients in low serum bilirubin group had significantly higher levels of systolic blood pressure, proteinuria, serum creatinine and crescent formation ratio and lower levels of serum albumin and hemoglobin. Renal survival analysis indicated that lower serum bilirubin levels were significantly correlated with a poorer prognosis. Multivariate Cox analysis demonstrated that the higher level of serum bilirubin was an independent protective factor for renal survival (HR, 0.172; 95% CI, 0.030-0.991; P = 0.049). After PS matching, the baseline characters of two groups had no statistical differences. Similar outcomes were demonstrated in K-M curve and the multivariate Cox analysis. Conclusion: Elevated bilirubin levels might be related to the favorable renal outcomes.

Global Glomerulosclerosis and Segmental Glomerulosclerosis Could Serve as Effective Markers for Prognosis and Treatment of IgA Vasculitis With Nephritis.

Background: This study was aimed at investigating the clinical significance and curative effect of global glomerulosclerosis (GS) and segmental glomerulosclerosis (S) in adult-onset IgA vasculitis with nephritis (IgAV-N) patients since there was no consensus pathological grading method for adult IgAV-N. Methods: A total of 188 biopsy-proven IgAV-N patients were prospectively identified. Patients were separately assigned to GS0/GS1/GS2 group and S0/S1/S2 based on the scores of global glomerulosclerosis and segmental glomerulosclerosis (0% /0-15% />15%, respectively). Results: GS0, GS1, and GS2 occurred in 56.4, 29.2, and 14.4% of the adult-onset IgAV-N, respectively. Patients in GS2 group tended to have the most serious renal deterioration and the highest levels of blood pressure. IgAV-N patients were also divided into S0 group (64.4%), S1 group (20.7%), and S2 group (14.9%), where no obvious differences in baseline data were noted. K-M curves indicated that GS2 group had the worst renal outcome (P = 0.05) while there seemed to be no significant differences between GS0 group and GS1 group. In addition, no remarkable differences in primary outcome were found among S0 group, S1 group, and S2 group though the prognosis of S2 group tended to be the worst. However, the prognosis of S0/S1 group was markedly better than that of S2 (P = 0.04). The discrimination of poor prognosis could be improved by adding the pathological indicators of global glomerulosclerosis and segmental glomerulosclerosis. Most importantly, immunosuppressive treatment might be a superior alternative in IgAV-N patients without sclerosis scores or with lower level of sclerosis scores. But addition of immunosuppression was not recommended in patients with higher sclerosis scores. Conclusions: Global glomerulosclerosis and segmental sclerosis might be used for management and treatment of adult-onset IgAV-N.

The efficacy and safety of immunosuppressive therapies in the treatment of IgA nephropathy: A network meta-analysis.

Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerulonephritis that can result in end-stage renal disease (ESRD). Whether immunosuppressants are superior or equivalent to supportive care is still controversial. A network meta-analysis was conducted to compare the efficacy and safety of immunosuppressive treatment for IgAN. Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and EMBASE were searched on December 30, 2018. We used a random-effects model with a Bayesian approach to appraise both renal outcomes and serious adverse effects. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated to present the relative effects. The ranking probabilities were calculated by the surface under the cumulative ranking curve (SUCRA). In total, 24 RCTs comprising 6 interventions were analyzed. Steroids significantly delayed the progression of renal deterioration with acceptable serious adverse effects, compared with supportive care (RR = 0.28, 95% CI = 0.13-0.51, SUCRA = 48.7%). AZA combined with steroids might be an alternative immunosuppressive therapy. Tacrolimus might decrease the proteinuria level (RR = 3.1, 95% CI = 1.2-9.4, SUCRA = 66.5%) but cannot improve renal function, and the side effects of tacrolimus should not be neglected. MMF and CYC showed no superiority in the treatment of IgAN. In summary, steroids might be recommended as the first-line immunosuppressive therapy for IgAN.

Immunomodulatory role of recombinant human erythropoietin in acute kidney injury induced by crush syndrome via inhibition of the TLR4/NF-κB signaling pathway in macrophages.

Objective: The present study aimed to investigate whether recombinant human erythropoietin (rHuEPO) plays an immunomodulatory function by regulating the TLR4/NF-κB signaling pathway.Materials and methods: C57BL/6 mice were intraperitoneally injected with rHuEPO and, half an hour later, with 50% glycerol at the dose of 7.5 ml/kg to induce crush syndrome (CS)-acute kidney injury (AKI). The levels of TNF-α, IL-1ß, IL-6, serum creatinine (Scr), and creatine kinase (CK) were measured. The kidney tissues were analyzed by HE staining, and macrophage infiltration was detected by immunohistochemistry. Double immunofluorescence staining, RT-qPCR, and western blotting were conducted to analyze TLR4/NF-κB p65 expression. Ferrous myoglobin was co-cultured with RAW264.7 cells to mimic crush injury and the production of proinflammatory cytokines. The expression levels of TLR4 and NF-κB p65 were measured.Results: In vivo study results revealed that rHuEPO ameliorated renal function, tissue damage, production of proinflammatory cytokines, and macrophage infiltration in the kidneys. The protein and mRNA expression levels of genes involved in the TLR4/NF-κB signaling pathway in CS-induced AKI mice were upregulated (p < .05). Meanwhile, the expression levels of TLR4, NF-κB p65, and proinflammatory cytokines in RAW264.7 cells were downregulated in CS-AKI mice injected with rHuEPO (p < .05).Conclusions: Our results demonstrated the immunomodulatory capacity of rHuEPO and confirmed that rHuEPO exerts protective effects against CS-induced AKI by regulating the TLR4/NF-κB signaling pathway in macrophages. Therefore, our findings highlight the therapeutic potential of rHuEPO in improving the prognosis of CS-AKI patients.

The Clinicopathological Characteristics of Henoch-Schönlein Purpura Nephritis with Presentation of Nephrotic Syndrome.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis involving the kidneys, with a lower incidence in adults. Meanwhile, nephrotic syndrome (NS) can appear in HSPN. However, the clinicopathological features and renal outcome of adult-onset HSPN presenting with NS (NS-HSPN) have not been well clarified. METHODS: A total of 191 HSPN patients were prospectively analyzed and comparisons were made between NS-HSPN and non-NS-HSPN. Multivariate Cox regression analysis was carried out to find the unfavorable factors of renal outcome of NS-HSPN. RESULTS: Among the 191 patients, 44 (23.0%) had NS-HSPN. Apart from edema and abdominal pain, patients with NS-HSPN tended to have lower levels of erythrocytes and hemoglobulin in blood as well as a greater number of erythrocytes in urine (p < 0.05). Mesangial proliferation was the most common pathological lesion in HSPN and the rates of crescent formation were significantly different, with 54.5% in NS-HSPN and 33.3% in non-NS-HSPN (p < 0.05). Notably, 18.2 and 4.8% of patients reached the composite endpoints in the NS-HSPN and non-NS-HSPN groups, respectively (p < 0.05), demonstrating that NS-HSPN patients were more likely to progress to end-stage renal disease and had a worse outcome. We also found that hypertension, estimated glomerular filtration rate (eGFR), cystatin, and tubular atrophy/interstitial fibrosis (HR > 1, p < 0.05) at onset were correlated with adverse outcome in NS-HSPN. CONCLUSION: NS-HSPN had more severe clinicopathological manifestations and poorer prognosis. The adverse predictors of NS-HSPN principally depend on clinicopathological presentation rather than on different therapies, and hypertension, eGFR, cystatin, and tubular atrophy/interstitial fibrosis can serve as independent risk factors in NS-HSPN.

The efficacy and safety of immunosuppressive agents plus steroids compared with steroids alone in the treatment of Henoch-Schönlein purpura nephritis: A meta-analysis.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is the most severe symptom of Henoch-Schönlein purpura. The role of immunosuppressive agents combined with steroids is controversial in treating HSPN. Our meta-analysis was performed to assess the efficacy and safety of the combined therapy in the treatment of HSPN compared with steroids alone. METHODS: Cochrane Library, Pubmed, Embase, and Web of Science were searched and Newcastle-Ottawa Scale was used to assess the quality of the literatures. Odds ratios (OR) and standard mean difference (SMD) with a 95% confidence interval (CI) were used for dichotomous and continuous variables. A random-effect model or fixed-effect analysis was applied according to heterogeneity. RESULTS: A total of 9 articles were selected in our study. HSPN patients treated with combined therapy demonstrated a significant increase in complete remission rates (OR = 1.95; 95% CI 1.17-3.23, P = 0.010) and total remission rates (OR = 2.30 95% CI 1.33-3.98, P = 0.003) when compared with steroids alone. Children seemed to benefit more from combined treatment (OR = 2.45; CI 1.20-5.02, P = 0.014) than adults (OR = 1.56; CI 0.76-3.20, P = 0.225). Additionally, immunosuppressants plus steroids had an advantage on decreasing proteinuria (SMD = 0.28; CI 0.05-0.52, P = 0.019) and increasing the level of serum albumin (SMD = 0.98; CI 0.35-1.60, P = 0.002). However, significant differences were not found in the estimated glomerular filtration rate (eGFR) and rates of side-effects. CONCLUSION: Administration of immunosuppressive agents combined with steroids may be a superior alternative for HSPN. Nevertheless, long-term, high-quality, large-sample, and multicenter RCTs are required to make the results more convincing.