23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          OBJECTIVES:

          The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB.

          METHODS:

          We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB.

          RESULTS:

          The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course.

          CONCLUSION:

          An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.

          Related collections

          Most cited references87

          • Record: found
          • Abstract: found
          • Article: not found

          NF-kappaB in renal inflammation.

          The NF-kappaB family of transcription factors regulates the induction and resolution of inflammation. Two main pathways, classical and alternative, control the nuclear translocation of NF-kappaB. Classical NF-kappaB activation is usually a rapid and transient response to a wide range of stimuli whose main effector is RelA/p50. The alternative NF-kappaB pathway is a more delayed response to a smaller range of stimuli resulting in DNA binding of RelB/p52 complexes. Additional complexity in this system involves the posttranslational modification of NF-kappaB proteins and an ever-increasing range of co-activators, co-repressors, and NF-kappaB complex proteins. Collectively, NF-kappaB regulates the expression of numerous genes that play a key role in the inflammatory response during human and experimental kidney injury. Multiple stimuli activate NF-kappaB through the classical pathway in somatic renal cells, and noncanonical pathway activation by TWEAK occurs in acute kidney injury. Under most test conditions, specific NF-kappaB inhibitors tend to reduce inflammation in experimental kidney injury but not always. Although many drugs in current use clinically influence NF-kappaB activation, there are no data regarding specific NF-kappaB inhibition in human kidney disease.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            X-linked hypercalciuric nephrolithiasis: clinical syndromes and chloride channel mutations.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Natural history of primary IgA nephropathy.

              Primary IgA nephropathy (IgAN) is the most frequent type of primary glomerulonephritis worldwide. The characteristic presentation is gross hematuria at the time of an infectious episode. A renal biopsy still is mandatory for the diagnosis. The natural history of the disease is characterized by clinical and pathologic progression over time, which can vary from a few years to more than 50 years. It is possible to make a broad prediction at the time of diagnosis of the long-term (20 years) risk of progressive chronic kidney disease, and then to end-stage renal disease requiring renal replacement therapy (20-year cumulative end-stage renal disease risk range, 14%-39%). The 3 major independent risk factors are arterial hypertension, proteinuria more than 1 g/d, and severe renal histopathologic lesions including hyalinosis, crescents, or defined by histopathologic scoring systems. When any clinical risk factors are present, patients should be targeted closely by appropriate treatments in the following order: (1) precise control of hypertension, (2) control of proteinuria when persisting for greater than 1 g/d, and (3) evidence-based treatment where available for severe lesions. This is a symptomatic treatment strategy because pathogenesis and etiology still remain unclear.
                Bookmark

                Author and article information

                Journal
                Clinics (Sao Paulo)
                Clinics (Sao Paulo)
                Clinics
                Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
                1807-5932
                1980-5322
                July 2012
                : 67
                : 7
                : 697-703
                Affiliations
                [I ]University of São Paulo, Faculty of Medicine of Ribeirão Preto, Department of Pathology, Ribeirão Preto/SP, Brazil.
                [II ]Faculty of Medicine of Triângulo Mineiro, Department of General Pathology, Uberaba/MG, Brazil.
                [III ]University of São Paulo, Faculty of Medicine of Ribeirão Preto, Division of Nephrology, Ribeirão Preto/SP, Brazil.
                [IV ]University of São Paulo, Faculty of Medicine of Ribeirão Preto, Department of Physiology, Ribeirão Preto/SP, Brazil.
                Author notes

                Silva GEB participated in the conception and drafting of the manuscript as well as the revisions for critically important intellectual content. Costa RS was involved in the histopathological studies of the biopsies from selected patients as well as the revision of the manuscript for critically important intellectual content. Ravinal RC participated in the immunohistochemical studies. Reis MA participated in the statistical analysis. Ramalho LZ participated in the Southwestern histochemical studies. Moyses-Neto M participated in the morphometric analyses. Romao EA participated in the translation and editing of the manuscript. Coimbra TM participated in the conception, analysis of data, and in the revision of the manuscript for critically important intellectual content. Dantas M participated in the selection of patients, collection of biopsies, analysis of data, laboratory and radiological exams, and in the revision of the manuscript for critically important intellectual content.

                E-mail: gyleanes@ 123456fmrp.usp.br Tel.: 55 16 3602-0224
                Article
                cln_67p697
                10.6061/clinics/2012(07)01
                3400157
                22892911
                9fcf9004-a83e-4484-87e9-672957542dbd
                Copyright © 2012 Hospital das Clínicas da FMUSP

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 February 2012
                : 29 February 2012
                : 5 March 2012
                Page count
                Pages: 7
                Categories
                Clinical Science

                Medicine
                macrophage,southwestern immunohistochemistry,glomerulonephritis,renal fibrosis,iga nephropathy

                Comments

                Comment on this article