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The aim of this study was to determine whether a correlation exists between interleukin-8 receptor polymorphisms and urinary tract infection (UTI) susceptibility. We systematically searched electronic databases including PubMed, Embase, China National Knowledge Infrastructure, and Web of Science up to November 5, 2017 to select appropriate studies that focused on C-X-C chemokine receptor type 1 and/or 2 (CXCR1, CXCR2) polymorphisms with susceptibility to UTI. Eight case-control studies including 2085 patients with UTI and 2012 controls were enrolled in this study. Seven studies of CXCR1 rs2234671 and two studies of rs3138086 were included in the meta-analyses. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were synthesized using fixed-effects or random-effects model according to heterogeneity. No significant correlations were found between CXCR1 rs2234671 and rs3138086 polymorphisms and UTI susceptibility. However, subgroup analysis showed that rs2234671 was associated with an increased risk of UTI under allelic comparisons (C vs. G, OR = 1.95, 95% CI = 1.07-3.55), heterozygous model (GC vs. GG, OR = 1.93, 95% CI = 1.06-3.50), and dominant model (GC+CC vs. GG, OR = 1.98, 95% CI = 1.07-3.69) in children, especially in pediatric patients with acute pyelonephritis (allelic, OR = 2.43, 95% CI = 1.28-4.60; heterozygous, OR = 2.40, 95% CI = 1.24-4.62; dominant, OR = 2.48, 95% CI = 1.26-4.88). Furthermore, these results remained the same after eliminating paediatric patients with vesicoureteral reflux. CXCR1 rs2234671 polymorphism might be associated with an increased risk of UTI in children.

BackgroundRecent data indicate the importance of gut-kidney axis in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Growing evidence suggests the alterations of diversity and composition of gut microbiome among patients with IgAN, however, the details are not yet fully understood.MethodsEligible studies comparing the gut microbiome between patients with IgAN and non-IgAN individuals were systematically searched from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov. The primary outcomes were alpha- and beta-diversity, and the differences in gut microbiota composition between patients with IgAN and non-IgAN persons. Qualitative analysis and meta-analysis were performed according to available data.ResultsEleven cross-sectional studies, including 409 patients with IgAN and 243 healthy controls, were enrolled. No significant differences in the diversity and enrichment of gut bacteria were found between IgAN and healthy individuals, whereas the beta-diversity consistently showed significant microbial dissimilarities among the two groups. Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia were the dominant phyla, however, no significant differences were found between IgAN patients and healthy controls at the phylum level. The genera, Streptococcus and Paraprevotella showed a higher proportion in patients with IgAN compared to healthy individuals, whereas Fusicatenibacter showed a lower abundance according to meta-analysis. Qualitative analyses suggested that Escherichia-Shigella might be increased in IgAN patients; the genera, Clostridium, Prevotella 9,and Roseburia, members of Ruminococcaceae and Lachnospiraceae families, were likely to have decreased abundances in patients with IgAN compared to healthy individuals.ConclusionGut microbiota dysbiosis was demonstrated in IgAN, which might be involved in the pathogenesis of IgAN. Further studies are needed to confirm the findings of this study, due to the substantial heterogeneity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022304034).

BackgroundGut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined.MethodsStudies comparing the differences of gut microbiome between patients with DKD and non-DKD individuals using high-throughput sequencing technology, were systematically searched and reviewed. Outcomes were set as gut bacterial diversity, microbial composition, and correlation with clinical parameters of DKD. Qualitative data were summarized and compared through a funnel R script, and quantitative data were estimated by meta-analysis.ResultsA total of 15 studies and 1640 participants were included, the comparisons were conducted between DKD, diabetes mellitus (DM), non-diabetic kidney disease (NDKD), and healthy controls. There were no significant differences of α-diversity between DKD and DM, and between DKD and NDKD, however, significant lower microbial richness was found in DKD compared to healthy controls. Different bacterial compositions were found between DKD and non-DKD subjects. The phylum Actinobacteria were found to be enriched in DKD compared to healthy controls. At the genus level, we found the enrichment of Hungatella, Bilophila, and Escherichia in DKD compared to DM, patients with DKD showed lower abundances of Faecalibacterium compared to those with NDKD. The genera Butyricicoccus, Faecalibacterium, and Lachnospira were depleted in DKD compared to healthy controls, whereas Hungatella, Escherichia, and lactobacillus were significantly enriched. The genus Ruminococcus torques group was demonstrated to be inversely correlated with estimated glomerular filtration rate of DKD.ConclusionsGut bacterial alterations was demonstrated in DKD, characterized by the enrichment of the genera Hungatella and Escherichia, and the depletion of butyrate-producing bacteria, which might be associated with the occurrence and development of DKD. Further studies are still needed to validate these findings, due to substantial heterogeneity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022340870.

Background: The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach.Methods: Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine.Results: Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17–1.93), MMF (RR 2.05, 95% CI 1.15–3.65), TAC (RR 3.67, 95% CI 1.06–12.63), and HCQ (RR 3.25, 95% CI 1.05–10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12–0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37–6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40–4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration.Conclusion: Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.

Objective. To explore the possible mechanisms of Ephedra herb (EH) in the treatment of nephrotic syndrome (NS) by using network pharmacology and molecular docking in this study. Methods. Active ingredients and related targets of EH were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the gene names corresponding to the proteins were found through the UniProt database. Then, target genes related to NS were screened out from GeneCards, PharmGKB, and OMIM databases. Next, the intersection targets were obtained successfully through Venn diagram, which were also seen as key target genes of EH and NS. Cytoscape 3.9.0 software was used to construct the effective “active ingredient-target” network diagram, and “drug-ingredient-target-disease (D-I-T-D)” network diagram. After that, the STRING database was used to construct a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment involved in the targets were performed by the DAVID database and ClueGO plugin in Cytoscape. Finally, AutoDockTools software was used for molecular docking to verify the binding strength between main active ingredients and key target proteins. Results. A total of 22 main active ingredients such as quercetin, kaempferol, luteolin, and naringenin were obtained, which could act on 105 targets related to NS. Through PPI network, 53 core targets such as AKT1, TNF, IL6, VEGFA, and IL1B were found, which might play a crucial role in the treatment of NS. Meanwhile, these targets were significantly involved in PI3K-Akt signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, hepatitis B, and pathways in cancer through GO and KEGG enrichment analysis. The docking results indicated that active ingredients such as kaempferol, luteolin, quercetin, and naringenin all had good binding to the target protein AKT1 or TNF. Among them, luteolin and naringenin binding with AKT1 showed the best binding energy (-6.2 kcal/mol). Conclusion. This study indicated that the potential mechanism of EH in treating NS may be related to PI3K-Akt signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway, which provided better approaches for exploring the mechanism in treating NS and new ideas for further in vivo and in vitro experimental verifications.

Primary nephrotic syndrome (PNS) is a common renal disease that presents with heavy proteinuria and hypoalbuminemia. Despite notable advances in its treatment, some patients show poor responses and clinical outcomes when treated with conventional Western medicine (WM). Chinese herbal injections (CHIs) have been reported to have beneficial effects for PNS. The aim of the present study was to comprehensively determine the efficacy and safety of CHIs for PNS in adults using a network meta-analysis approach. PubMed, Embase, the Cochrane library, and four Chinese databases were systematically searched to identify randomized controlled trials (RCTs) using CHIs for treatment of PNS published before June 1, 2019. Quality assessment of the identified RCTs was performed according to the Cochrane Handbook. Pooled odds ratios (OR) or mean differences (MD) with corresponding 95% confidence intervals (CI) were calculated for discrete or continuous variables, respectively. The primary outcome was complete/total remission and secondary outcomes were serum albumin and urinary protein excretion. The surface under the cumulative ranking curve (SUCRA) value and cluster analyses were used to rank treatment by probability. Eighty-five studies involving 11 CHIs and 5801 subjects were included. Compared with WM alone, CHI plus WM showed an improved complete/total remission rate as well as higher serum albumin and lower 24-hour urinary protein excretion, except in the following: Yinxingye injection plus WM did not improve the total remission rate, and Dengzhanhua or Xueshuantong injection plus WM did not lower the 24-hour urinary protein excretion. Either Danhong (DH) or Dengzhanhua (DZH) injection plus WM was the preferable treatment for PNS based on SUCRA and cluster analyses of clinical remission and adverse events. However, considering that literature in this area is limited, these results need further validation. CHIs administered as adjuvants to WM showed favourable outcomes for PNS. DH + WM and DZH + WM might be the potential optimal therapies for PNS.

Podocyte is also called glomerular epithelial cell, which has been considered as the final gatekeeper of glomerular filtration barrier (GFB). As a major contributor to proteinuria, podocyte injury underlies a variety of glomerular diseases and becomes the challenge to patients and their families in general. At present, the therapeutic methods of podocyte injury mainly include angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, steroid and immunosuppressive medications. Nevertheless, the higher cost and side effects seriously disturb patients with podocyte injury. Promisingly, traditional Chinese medicine (TCM) has received an increasing amount of attention from different countries in the treatment of podocyte injury by invigorating spleen and kidney, clearing heat and eliminating dampness, as well enriching qi and activating blood. Therefore, we searched articles published in peer-reviewed English-language journals through Google Scholar, PubMed, Web of Science, and Science Direct. The protective effects of active ingredients, herbs, compound prescriptions, acupuncture and moxibustion for treatment of podocyte injury were further summarized and analyzed. Meanwhile, we discussed feasible directions for future development, and analyzed existing deficiencies and shortcomings of TCM in the treatment of podocyte injury. In conclusion, this paper shows that TCM treatments can serve as promising auxiliary therapeutic methods for the treatment of podocyte injury.