Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids.
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ABSTRACT:
SUBMITTER: Tamzali Y
PROVIDER: S-EPMC9366361 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids.
Tamzali Yanis Y Buob David D Verdet Charlotte C Luque Yosu Y Mesnard Laurent L Boffa Jean-Jacques JJ Esteve Emmanuel E
Kidney international reports 20220606 8
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Project description:BackgroundAcute pyelonephritis (APN) versus acute rejection (AR) is a frequently encountered diagnostic and therapeutic dilemma in kidney transplants. Variable culture results, overlapping histologic features, and persistent graft dysfunction despite antibiotics are frequently encountered. Therefore, we explored the utility of intragraft microRNA profiles to distinguish between allograft APN and AR.Materials and methodsBetween 2003 and 2011, we identified 49 patients with biopsy features of APN, within the first 2 years posttransplant. MicroRNA profiling was performed on 20 biopsies (normal kidney, n=4; unequivocal AR, n=5; features of APN, n=11).ResultsOnly 32% (16/49) of the patients had concomitant positive urine cultures at biopsy, and in 8 of 16 patients, colony count was less than 10 CFU/mL. In 14 of 49 patients, positive urine culture did not coincide with the biopsy, and in 19 of 49 patients, urine cultures were negative. On microRNA profiling, good clustering was seen among the normal kidneys and among AR biopsies. Among the 11 biopsies with features of APN, 4 biopsies showed good clustering with a pattern distinct from AR; (these patients recovered graft function with antibiotics); 7 of 11 biopsies showed heterogeneity in microRNA profiles and variable outcomes with antibiotic treatment. We identified a panel of 25 microRNAs showing statistical difference in expression between AR and APN. MiR-99b, miR-23b let-7b-5p, miR-30a, and miR-145 were validated using qPCR.ConclusionAllograft pyelonephritis can be a diagnostic and therapeutic challenge. A gestalt approach is required. In addition to histology and cultures, differential intragraft microRNA expression may prove helpful to distinguish APN from AR in renal allograft biopsies.
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Project description:Enterovirus-specific genetic sequences were isolated from two Amblyomma americanum tick pools. Identical genetic sequences were later obtained from cerebrospinal fluid of a patient with aseptic meningitis and a recent history of tick attachment. These observations suggest the possibility of an emerging tick-borne human enterovirus associated with aseptic meningitis.
| S-EPMC1169181 | biostudies-literature
Project description:Dendritic cells (DCs) are the most abundant immune cells in the kidney and form an intricate network in the tubulointerstitium, suggesting that they may play an important role in interstitial infections such as pyelonephritis. Here, we optimized a murine pyelonephritis model by instilling uropathogenic Escherichia coli two times at a 3-hour interval, which produced an infection rate of 84%. By 3 hours after the second instillation, resident kidney DCs began secreting the chemokine CXCL2, which recruits neutrophilic granulocytes. During the time studied, DCs remained responsible for most of the CXCL2 production. Neutrophils began infiltrating the kidney 3 hours after the second instillation and phagocytozed bacteria. Macrophages followed 3 hours later and contributed much less to both CXCL2 production and bacterial phagocytosis. To investigate whether DCs recruit neutrophils into the kidney for antibacterial defense, we used CD11c.DTR mice allowing conditional depletion of CD11c(+) dendritic cells. The absence of CD11c(+) DCs markedly delayed neutrophil recruitment and bacterial clearance. In conclusion, these findings suggest that the tubulointerstitial dendritic cell network serves an innate immune sentinel function against bacterial pyelonephritis.
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Project description:BackgroundFor unknown reasons, urinary tract infections (UTIs) are clustered in certain individuals. Here we propose a novel, genetically determined cause of susceptibility to acute pyelonephritis, which is the most severe form of UTI. The IL-8 receptor, CXCR1, was identified as a candidate gene when mIL-8Rh mutant mice developed acute pyelonephritis (APN) with severe tissue damage.Methods and findingsWe have obtained CXCR1 sequences from two, highly selected APN prone patient groups, and detected three unique mutations and two known polymorphisms with a genotype frequency of 23% and 25% compared to 7% in controls (p<0.001 and p<0.0001, respectively). When reflux was excluded, 54% of the patients had CXCR1 sequence variants. The UTI prone children expressed less CXCR1 protein than the pediatric controls (p<0.0001) and two sequence variants were shown to impair transcription.ConclusionsThe results identify a genetic innate immune deficiency, with a strong link to APN and renal scarring.
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Project description:C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein. In addition to myeloid cells, C5aR1 is expressed on epithelial cells. In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role. We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC). This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice. Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium. In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling. Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
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Project description:Activated mononuclear cells are an early event in the course of severe acute pancreatitis (SAP). To date, the molecular mechanism triggering peripheral blood mononuclear cells (PBMCs) is poorly understood. The aim of this paper was to determine the potential role of Card9 in SAP. We collected data from 72 subjects between January 2013 and June 2014. Subsequently, PBMCs were isolated on day 1, 3 and 5 of pancreatitis. Immunofluorescence staining, quantitative real-time PCR, Western blotting, immunoprecipitation and ELISA were used to determine the role of Card9 in SAP. Microbial culture showed that SAP patients at the early period did not develop any bacteria and fungi infection. Card9 expression in SAP patients was higher than that in mild acute pancreatitis and volunteer healthy controls, up to the peak on day 1. The monocyte-derived cytokines interleukin (IL)-17, IL-1β, IL-6 and tumour necrosis factor-α mediated by the induction of Card9 markedly increased in SAP patients compared with the control group. Furthermore, the inducible formation of Card9-Bcl10 complex was found in PBMCs, which may be involved in nuclear factor kappa B (NF-κB) and p38 activation in SAP. Receiver operating characteristic curve indicated that Card9 levels had a high sensitivity of 87.5% and specificity of 67.7%, showing the close correlation with SAP patients. Card9 overexpression was firstly found in aseptic SAP, which may be played an important role in NF-κB and p38 activation in PBMCs. It also provided the new insights into therapeutic interventions by targeting monocytes activation in SAP patients.
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Project description:The pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated CpGs. Further investigation has identified many other types of DNA sensors distributed in a variety of cellular compartments. These sensors not only sense foreign DNAs, including bacterial and viral DNAs, but also sense damaged DNAs from the host cells. The major downstream signalling pathways includeTLR-9-MyD88-IKKa-IRF-7/NF-?B pathways to increase IFN/proinflammatory cytokine production, STING-TBK1-IRF3 pathway to increase IFN-beta, and AIM2-ASC-caspas-1 pathway to release IL-1beta. The major outcome is to activate host immune response by inducing cytokine production. In this review, we focus on the roles and potential mechanisms of DNA sensors and downstream pathways in sepsis. Although bacterial DNAs play important roles in sepsis development, bacterial DNAs alone are unable to cause severe disease nor lead to death. Priming animals with bacterial DNAs facilitate other pathological factors, such as LPS and other virulent factors, to induce severe disease and lethality. We also discuss compartmental distribution of DNA sensors and pathological significance as well as the transport of extracellular DNAs into cells. Understanding the roles of DNA sensors and signal pathways will pave the way for novel therapeutic strategies in many diseases, particularly in sepsis.
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Project description:ObjectiveTo determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis.Study designWe enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes.ResultsUrinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis.ConclusionsImmune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.
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Project description:ObjectiveWNT5A is one of the most studied noncanonical WNT ligands and is shown to be deregulated in different tumor types. Our aim was to clarify whether hypermethylation might be the cause of low WNT5A mRNA levels and whether we could restore this downregulation by reversing the event.Materials and methodsThe expression of WNT5A mRNA was studied in a large acute lymphoblastic leukemia (ALL) patient group (n=86) by quantitative real-time PCR. The methylation status was detected by methylation-specific PCR (MSPCR) and bisulphate sequencing. In order to determine whether methylation has a direct effect on WNT5A expression, disease-representative cell lines were treated by 5'-aza-20-deoxycytidine.ResultsHere we designed a validation experiment of the WNT5A gene, which was previously examined and found to be differentially expressed by microarray study in 31 T-cell ALL patients. The expression levels were confirmed by quantitative real-time PCR and the expression levels were significantly lower in T-cell ALL patients than in control thymic subsets (p=0.007). MSPCR revealed that 86% of the patients were hypermethylated in the WNT5A promoter region. Jurkat and RPMI cell lines were treated with 5'-aza-20-deoxycytidine and WNT5A mRNA expression was restored after treatment.ConclusionAccording to our results, WNT5A hypermethylation does occur in ALL patients and it has a direct effect on mRNA expression. Our findings show that epigenetic changes of WNT signaling can play a role in ALL pathogenesis and reversing methylation might be useful as a possible treatment of leukemia.
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Project description:BackgroundBacterial keratitis is a serious ocular infectious disease that can lead to severe visual disability. Risk factors for bacterial corneal infection include contact lens wear, ocular surface disease, corneal trauma and previous ocular or eyelid surgery. Topical antibiotics constitute the mainstay of treatment in cases of bacterial keratitis where as the use of topical corticosteroids remains controversial. Topical corticosteroids are usually used to control inflammation using the smallest amount of the drug. Their use requires optimal timing, concomitant antibiotics and careful follow up.ObjectivesThe objective of the review was to assess the clinical effectiveness and adverse effects of corticosteroids as adjunctive therapy for bacterial keratitis.Search strategyWe searched CENTRAL, MEDLINE, EMBASE, and LILACS up to 15 January 2007. We also searched the Science Citation Index to identify additional studies that had cited the included trial, an online database of ongoing trials (www.clinicaltrials.gov), reference lists of included trials, earlier reviews and the American Academy of Ophthalmology guidelines. We also contacted experts to identify any unpublished and ongoing randomized trials.Selection criteriaWe included randomized controlled trials evaluating adjunctive therapy with topical corticosteroids in people with bacterial keratitis.Data collection and analysisTwo review authors independently screened all the retrieved articles. Methodological quality of the one included trial was assessed using forms developed using pre-specified criteria by at least two review authors. We planned to extract data on outcomes using forms developed for the purpose. We planned to report risk ratios for dichotomous outcomes and mean differences for continuous outcomes.Main resultsA single trial was eligible for inclusion in the review. Participants in the trial were randomized using a random numbers table. Allocation concealment was not attempted. Masking of participants, and care-providers was also not attempted. Outcome assessment was conducted independently by two physicians. Neither was masked to the treatment allocation. The trial reported the healing rate of epithelial defects and improvement in visual acuity.Authors' conclusionsThere are no good quality randomized trials evaluating the effects of adjunct use of topical corticosteroids in bacterial keratitis. The only randomized trial we identified in the literature suffered from major methodological inadequacies.
| S-EPMC4374569 | biostudies-literature