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1.
Nephrol Dial Transplant ; 36(8): 1452-1463, 2021 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-32639002

RESUMEN

BACKGROUND: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. METHODS: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. RESULTS: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. CONCLUSIONS: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Antígenos CD/orina , Glomerulonefritis , Anticuerpos Anticitoplasma de Neutrófilos , Antígenos de Diferenciación Mielomonocítica , Antígeno CD11b , Glomerulonefritis/diagnóstico , Humanos , Riñón , Receptores de Superficie Celular
2.
Kidney Int ; 95(3): 680-692, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30712924

RESUMEN

Noninvasive biomarkers of disease activity are needed to monitor response to therapy and predict disease recurrence in patients with glomerulonephritis. The leukocyte surface markers integrin Mac-1 and CD16b have been implicated in the pathogenesis of lupus nephritis (LN). Mac-1 comprises a unique α subunit (CD11b) complexed with a common ß2 subunit, which are released along with CD16b from specific leukocyte subsets under inflammatory conditions including glomerulonephritis. We investigated the association of urinary CD11b and CD16b with histopathological activity in 272 patients with biopsy-proven glomerular diseases, including 118 with LN. Urine CD11b and CD16b were measured via enzyme-linked immunosorbent assay. Urinary levels of both markers were increased in LN, but only urinary CD11b was correlated with the number of glomerular leukocytes and with overall histopathological activity. In a subset of patients with samples available from the time of biopsy and subsequent clinical remission of LN, urinary levels of CD11b decreased with successful glucocorticoid treatment. Receiver-operating characteristic curve analysis demonstrated that urinary CD11b was superior to CD16b, the scavenger receptor CD163, and monocyte chemotactic protein-1 for the prediction of proliferative LN. In anti-mouse nephrotoxic serum glomerulonephritis, urinary CD11b correlated with histologic damage and decreased with corticosteroid treatment. In vitro, CD11b levels were decreased on activated mouse neutrophils displaying Fcγ receptor clustering and transendothelial migration, suggesting that leukocyte activation and transmigration are required for CD11b shedding in urine. Together, our results suggest that urinary CD11b may be a useful biomarker to estimate histopathological activity, particularly glomerular leukocyte accumulation, in LN.


Asunto(s)
Antígeno CD11b/análisis , Glomérulos Renales/inmunología , Nefritis Lúpica/diagnóstico , Adulto , Anciano , Animales , Biomarcadores/análisis , Antígeno CD11b/inmunología , Modelos Animales de Enfermedad , Femenino , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/orina , Glucocorticoides/uso terapéutico , Humanos , Glomérulos Renales/citología , Glomérulos Renales/patología , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/orina , Masculino , Ratones , Persona de Mediana Edad , Neutrófilos/inmunología , Curva ROC , Receptores de IgG/inmunología , Adulto Joven
3.
Am J Pathol ; 186(12): 3176-3188, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27855848

RESUMEN

Macrophages are multifunctional immune cells that may either drive or modulate disease pathogenesis, depending on the activated phenotype. In this study, we investigated the protective effects of CD206+ M2 macrophages against nephrotoxic serum nephritis in mice. We found that these immunosuppressive macrophages, derived from bone marrow and stimulated with IL-4/IL-13 [CD206+ M2 bone marrow-derived macrophages (M2BMMs)], protected against renal injury, decreased proteinuria, and diminished the infiltration of CD68+ macrophages, neutrophils, and T cells into glomerular tissue. Comparable therapeutic results were obtained with CD206+ M2 cells derived from induced pluripotent stem cells. Notably, CD206+ M2BMMs, which retained an M2 signature, could elicit a switch of M1 to M2 phenotype in co-cultured macrophages. Moreover, these cells were found to induce the production of regulatory T cells in the spleen and renal draining lymph node. Accordingly, mRNA expression of the T helper 1 cytokines tumor necrosis factor-α, interferon-ß, interferon-γ, and IL-12 was significantly reduced in kidneys from mice treated with CD206+ M2BMMs. Taken together, the data suggest that CD206+ M2 may have therapeutic potential against antibody-mediated glomerular injury and presents its therapeutic value for the treatment of crescentic nephritis in humans.


Asunto(s)
Anticuerpos/efectos adversos , Citocinas/inmunología , Glomerulonefritis/terapia , Lectinas Tipo C/inmunología , Macrófagos/inmunología , Lectinas de Unión a Manosa/inmunología , Receptores de Superficie Celular/inmunología , Animales , Técnicas de Cocultivo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Glomerulonefritis/inmunología , Glomerulonefritis/fisiopatología , Humanos , Riñón/inmunología , Riñón/fisiopatología , Glomérulos Renales/inmunología , Glomérulos Renales/fisiopatología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/fisiopatología , Macrófagos/trasplante , Masculino , Receptor de Manosa , Ratones , Ratones Endogámicos C57BL , Bazo/inmunología , Bazo/fisiopatología , Linfocitos T Reguladores/inmunología , Células TH1/inmunología
4.
Nephrol Dial Transplant ; 31(12): 2023-2033, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27242373

RESUMEN

BACKGROUND: In addition to classically activated macrophages that have effector roles in tissue injury, alternatively activated M2 macrophages are involved in the resolution of inflammation in animal models of kidney disease. To clarify the clinical relevance of macrophage phenotypes in human glomerular diseases, we evaluated the renal accumulation of macrophages and plasma and urine levels of CD163, an M2 marker, in lupus nephritis (LN) patients. METHODS: Kidney biopsies and plasma and urine samples were obtained from LN patients who underwent renal biopsy between 2008 and 2012. CD163+, CD68+ and CD204+ cells were counted in paraffin-embedded and frozen sections. LN histological activity was evaluated semiquantitatively using the biopsy activity index. Plasma and urinary soluble CD163 (sCD163) concentrations were also measured and evaluated for their significance as potential LN biomarkers. RESULTS: Immunohistological analysis of glomeruli from LN patients revealed that >60% of CD68+ macrophages had merged with CD163+ cells. The increased number of glomerular CD163+ macrophages was correlated with LN severity, as determined by the biopsy active index (r = 0.635). Urinary (u-) sCD163 level was strongly correlated with glomerular CD163+ cell counts and histological disease score as well as urinary monocyte chemoattractant protein 1 levels (r = 0.638 and 0.592, respectively). Furthermore, the u-sCD163 level was higher in patients with active LN than in those with other diseases. CONCLUSIONS: Glomerular CD163+ macrophages are the predominant phenotype in the kidneys of lupus patients. These findings indicate that the u-sCD163 level can serve as a biomarker for macrophage-dependent glomerular inflammation in human LN.


Asunto(s)
Antígenos CD/orina , Antígenos de Diferenciación Mielomonocítica/orina , Inflamación/diagnóstico , Glomérulos Renales/inmunología , Nefritis Lúpica/complicaciones , Macrófagos/inmunología , Adulto , Anciano , Biomarcadores/orina , Estudios de Cohortes , Femenino , Humanos , Inflamación/etiología , Inflamación/orina , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Persona de Mediana Edad , Fenotipo , Receptores de Superficie Celular
5.
Intern Med ; 60(12): 1893-1897, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33456038

RESUMEN

A 71-year-old Japanese man with progressive kidney failure was referred to our hospital. Laboratory tests showed elevated IgG4 levels. Contrast-enhanced computed tomography (CT) revealed soft tissue surrounding the left kidney and right atrophic kidney. A histopathological examination revealed inflammation and fibrosis with rich IgG4-positive cells in the thickened kidney capsule, but not in the kidney parenchyma. Poor enhancement in the left kidney on contrast-enhanced CT and wrinkling of glomerular capillaries in pathological tissues were also observed. These findings indicated IgG4-related perirenal lesions leading to low renal perfusion and kidney failure. The perirenal lesions and kidney failure were improved by corticosteroid therapy.


Asunto(s)
Enfermedad Relacionada con Inmunoglobulina G4 , Enfermedades Renales , Insuficiencia Renal , Anciano , Humanos , Inmunoglobulina G , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Riñón/diagnóstico por imagen , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/etiología , Masculino , Insuficiencia Renal/etiología
6.
Nagoya J Med Sci ; 82(4): 775-781, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33311807

RESUMEN

Myocardial calcification secondary to acute myocarditis is a rare but possibly life-threatening complication. We report a 43-year-old woman with minimal change nephrotic syndrome who developed sepsis caused by Escherichia coli. We simultaneously detected the complication of acute myocarditis in the patient. Although echocardiography showed hypokinesis of the apical segment when acute myocarditis was diagnosed, no sign of myocardial calcification was observed. After two weeks, a CT showed myocardial calcification in the same area. Although myocardial calcification was still observed 12 months later, the patient's cardiac function had improved.


Asunto(s)
Calcinosis , Cardiomiopatías , Infecciones por Escherichia coli , Miocarditis , Sepsis , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Adulto , Antibacterianos/uso terapéutico , Calcinosis/diagnóstico por imagen , Calcinosis/etiología , Cardiomiopatías/diagnóstico , Cardiomiopatías/etiología , Cardiomiopatías/fisiopatología , Ecocardiografía/métodos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/etiología , Infecciones por Escherichia coli/fisiopatología , Infecciones por Escherichia coli/terapia , Femenino , Pruebas de Función Cardíaca , Hemodiafiltración/métodos , Humanos , Miocarditis/etiología , Miocarditis/microbiología , Miocarditis/fisiopatología , Nefrosis Lipoidea/complicaciones , Sepsis/complicaciones , Sepsis/microbiología , Sepsis/terapia , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
7.
CEN Case Rep ; 6(2): 194-199, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28895103

RESUMEN

Extramedullary hematopoiesis (EMH) is hematopoiesis in organs outside the bone marrow and most frequently occurs in the liver, spleen, and lymph nodes. We report a case of perirenal EMH revealed by kidney biopsy in a patient with primary myelofibrosis. We observed only bilateral kidney enlargement with plain computed tomography (CT) and ultrasonography before obtaining a renal biopsy. We obtained a percutaneous biopsy from the lower pole of the left kidney using ultrasonographic guidance. Ultrasonography just after the renal biopsy revealed no bleeding around the kidney. However, early the next morning, the patient developed severe hemorrhagic shock. Contrast-enhanced CT at that time revealed a massive hematoma in the left posterior perirenal space and bilateral abnormalities of the perirenal soft tissues. In patients with primary myelofibrosis, if plain CT shows an abnormal renal enlargement, EMH should be considered. In addition, a contrast-enhanced CT should be obtained before performing a percutaneous renal biopsy to assess for the possibility of perirenal EMH in these patients.

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