Background and objectiveHenoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP.MethodsPubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD).ResultsThirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61–1.19); age > 10 y (3.13, 1.39–7.07); male gender (1.36, 1.07–1.74); abdominal pain (1.94,1.24–3.04); gastrointestinal bleeding (1.86, 1.30–2.65); severe bowel angina (3.38, 1.17–9.80); persistent purpura (4.02, 1.22–13.25); relapse (4.70, 2.42–9.14); WBC > 15 × 109/L (2.42, 1.39–4.22); platelets > 500 × 109/L (2.98, 1.22–7.25); elevated antistreptolysin O (ASO) (2.17, 1.29–3.64); and decreased complement component 3 (C3) (3.13, 1.62–6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01–1.96).ConclusionThe following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early stages of HSP. However, the results should be interpreted cautiously due to the limitations of the studies.

Background There is limited information available regarding the clinical management of intravenous immunoglobulin-resistant Kawasaki disease (KD). We aimed to evaluate the optimal treatment options for patients with refractory KD by presenting an indirect-comparison meta-analysis. Methods PubMed, EMBASE, Web of Science, and the Cochrane Database were searched on August 31, 2018. Unpublished studies were also searched in ProQuest Dissertations & Theses and through manual retrieval strategies. Randomized concurrent controlled trials (RCTs), high-quality non-randomized concurrent controlled trials (non-RCTs), and retrospective studies associated with AEs were included. The quality of all eligible studies was assessed using Cochrane collaboration’s tool and non-randomized study guidelines. Risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous outcomes were estimated in our analysis. GRADE profiler 3.6.1 was used to assess the evidence profile. Results Twelve studies involving 372 immunoglobulin-resistant KD patients were identified and analyzed. Neither infliximab nor intravenous pulse methylprednisolone (IVMP) was significantly more effective than second IVIG infusion with respect to lowering coronary artery lesions (CALs) (infliximab, 0.85, 0.43–1.69; IVMP, 0.99, 0.52–1.88) and treatment resistance (infliximab, 0.43, 0.21–0.89; IVMP, 1.16, 0.33–4.13). No significant differences were found between infliximab and IVMP in the incidence rate of CALs (0.70, 0.27–1.81), the treatment resistance (0.37, 0.09–1.60), the rates of coronary artery aneurysm (4.13, 0.38–45.22) and the coronary artery dilatation (0.45, 0.10–1.99). Furthermore, compared with second IVIG infusion, both infliximab and IVMP showed significant effectiveness in antipyretic effects (infliximab, 1.52, 1.16–1.99; IVMP, 1.29, 0.77–2.15). However, Infliximab was noninferior to IVMP on antipyretic effects (1.18, 0.66–2.15). IVMP treatment showed significant association with fewer AEs than second IVIG infusion (0.49, 0.26–0.94) and infliximab (2.34, 1.07–5.09). No significant differences were noted between infliximab treatment and second IVIG infusion (1.06, 0.69–1.63). Conclusions Infliximab, IVMP, and second IVIG infusion showed no significant differences in the cardioprotective effect or the rate of treatment resistance. Infliximab and IVMP treatment were more effective than second IVIG infusion regarding antipyretic effects. IVMP treatment may have an advantage due to its lower total rate of AEs associated with drug infusion. Trial registration The study has been registered on PROSPERO ( CRD42016039693 ). Electronic supplementary material The online version of this article (10.1186/s12887-019-1504-9) contains supplementary material, which is available to authorized users.

BackgroundCD36 plays a critical role in many sterile inflammatory diseases, including type 2 diabetes mellitus, atherosclerosis, and primary nephrotic syndrome. This study investigated whether CD36 activates the nucleotide-binding domain leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and promotes podocytes apoptosis in primary nephrotic syndrome.Material/MethodsThe mouse podocyte cell line MPC5 was used as a model. mRNA and protein expression of CD36 and NLRP3 was quantified by real-time PCR and Western blotting, respectively. Levels of caspase-1 activity and total cholesterol were determined using commercial kits. Intracellular lipid droplets were detected by Oil Red O staining. CD36 expression was also examined in nephrotic mouse kidney tissue by immunohistochemistry and immunofluorescence. Intracellular lipid droplet was examined by Oil Red O staining.ResultsCD36 expression was increased in nephrotic mouse kidney tissue. Treatment with interleukin-1β increased expression of CD36 and total cholesterol in MPC5 cells. Moreover, this treatment increased expression of NLRP3 and the percentage of apoptotic cells, both of which were inhibited by co-treatment with an anti-CD36 antibody.ConclusionsCD36 might play an important role in podocyte apoptosis by activating the NLRP3 inflammasome in primary nephrotic syndrome.

The aim of this article is to investigate whether interleukin-1β (IL-1β) could regulate the intracellular accumulation of cholesterol and the expression of lipid-metabolism-related regulators in podocytes in vitro and the potential mechanisms. Podocytes were treated with 200 μg/ml of low-density protein (LDL), 20 ng/ml of IL-1β, or 200 μg/ml of LDL plus 5-20 ng/ml of IL-1β for 24 h in vitro. The contents of intracellular cholesterol were determined by enzymatic assays and Oil Red O staining. The levels of LDL receptor (LDLr), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, sterol regulatory element binding protein 2 (SREBP-2), SREBP cleavage activating protein (SCAP), and insulin-induced gene-1 (Insig-1) expression were characterized by real-time polymerase chain reaction (RT-PCR) and Western blot assays. Treatment with IL-1β or LDL alone increased the contents of intracellular cholesterol (P < 0.05 for both) and lipid droplets, and treatment with both IL-1β and LDL further increased the accumulation of intracellular cholesterol in podocytes (P < 0.05 vs. LDL alone). While loading with LDL significantly inhibited the expression of LDLr, HMG-CoA reductase, nuclear SREBP-2 (nSREBP-2), SCAP, and Insig-1 by 40-62% treatment with IL-1β enhanced the expression of LDLr, HMG-CoA reductase and nSREBP-2, but not Insig-1, in podocytes (P < 0.05 vs. control). Treatment with both LDL and IL-1β significantly increased the levels of LDLr and HMG-CoA reductase expression and the ratio of SCAP to Insig-1, as compared with that in the LDL-treated podocytes (P < 0.05 vs. LDL alone). Our data indicated that IL-1β mitigated the LDL-triggered SCAP-SREBP-2-mediated feedback inhibition on the expression of LDLr and HMG-CoA reductase, leading to the intracellular accumulation of LDL-cholesterol in podocytes in vitro.