Acute antibody-mediated rejection of renal transplant associated with cellular crescents: First case report

Acute antibody-mediated rejection is characterized by histological abnormalities such as glomerulitis, capillaritis, or thrombosis associated with presence of C4d and specific anti-donor antibodies. Reports on the association of glomerular injuries with cellular crescents in antibody-mediated rejection are not found in the literature. We report a unique case of antibody-mediated rejection associated with cellular crescents and suggest that such histological abnormality should be considered in the differential diagnosis of acute antibody-mediated rejection. © 2011 Elsevier Inc.

Hipertensão arterial sistêmica e sua correlação com as lesões renais de cães naturalmente acometidos por leishmaniose visceral

Pós-graduação em Ciência Animal - FMVA

Leishmaniose visceral canina: aspectos clínico-laboratoriais, histopatologia renal e testes específicos para diagnóstico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Histopatologia da série eritróide da medula óssea e do tecido renal de cães com insuficiência renal crônica

Pós-graduação em Medicina Veterinária - FMVZ

Alterações morfológicas e funcionais dos rins de cães com insuficiência renal crônica

Pós-graduação em Medicina Veterinária - FCAV

Estudo epidemiológico descritivo dos pacientes atendidos na unidade de hemodiálise do Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP

Pós-graduação em Enfermagem (mestrado profissional) - FMB

Pesquisa e genotipagem do vírus da hepatite C em portadores de doenças renais crônicas submetidos à hemodiálise

Pacientes com doença renal crônica tem alto risco de adquirir o vírus da hepatite C (VHC). A prevalência de hepatite C em unidades de hemodiálise é elevada. O estudo teve por objetivo avaliar a presença do VHC e seus diferentes genótipos em portadores de doença renal crônica que realizaram hemodiálise em Belém e região metropolitana, no Estado do Pará, Brasil, determinando a prevalência do vírus, genótipos e as características epidemiológicas dos portadores da doença renal crônica. Foi realizado um estudo transversal, em sete unidades de hemodiálise das cidades de Belém e região metropolitana, no período de outubro de 2011 a abril de 2012. Foi aplicado um questionário com dados sociais, epidemiológicos e sobre a presença de fatores de risco para hepatites virais. Material biológico foi coletado dos pacientes para os exames ELISA e PCR VHC. Os pacientes com presença de RNA viral foram avaliados quanto aos genótipos. A prevalência dos anticorpos para VHC entre os indivíduos estudados foi de 8,4%, enquanto 5,4% apresentaram RNA viral, com 0,1% entre os não reagentes. O genótipo 1 foi o mais prevalente, com 86,1%, seguido do tipo 2, com 11,6%. O tipo 3 teve somente 2,3%. A análise epidemiológica mostrou predomínio do sexo masculino, faixa etária de 49 anos, casados ou em união estável, com baixo nível de escolaridade e renda familiar de até 2 salários mínimos. A principal causa da doença renal crônica foi o diabetes mellitus (34,4%), seguida de glomerulonefrites (18,6%) e hipertensão arterial (17,1%). O tempo de hemodiálise foi significativamente importante fator de risco para aquisição do VHC (p=0,012), com a maioria dos portadores do VHC que adquiriram a doença durante hemodiálise estava acima de 5 anos de tratamento (p= 0,0001). Outro fator de risco associado ao VHC foi transplante de órgão prévio. Conclui-se que, em Belém e região metropolitana, a prevalência de VHC em hemodiálise foi elevada e o genótipo mais frequente é o mesmo da população geral no norte do Brasil.

Streptococcal acute pharyngitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphological, immunohistochemical and molecular study of renal lesions in canine visceral leishmaniasis (CVL)

Canine visceral leishmaniasis (CVL) is an anthropozoonosis characterized by a clinically chronic progressive disease. Non lymphoid organs are also affected, especially the kidneys. Dogs with leishmaniasis usually die with renal failure despite treatment. Haematoxylin-eosin (HE) staining in kidney tissue sections has low sensitivity for parasite identification. Immunohistochemistry (IHC) and polymerase chain reaction (PCR) are efficient methods for Leishmania sp. antigen and DNA detection in cases of low parasite burden. The present study aims to identify renal lesions of CVL and correlate them with microscopic findings determined by histochemistry, IHC and PCR. Both IHC and PCR provided similar positivity for amastigote identification, 3/20 animals (15%), thus increasing detection of the parasite in renal tissues when compared with histopathologic examination. The lesion most commonly observed with visceral leishmaniasis-positive canine kidney tissue was membranoproliferative glomerulonephritis, followed by interstitial nephritis without correlation to the number of amastigotes.

Urinary MCP-1 and RBP: Independent predictors of renal outcome in macroalbuminuric diabetic nephropathy

Background: Albuminuria has been considered a sine qua non condition for the diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate outcome of chronic kidney disease (CKD). However, recent data suggest that albuminuria may fail as a biomarker in a subset of patients, and the search for novel markers is intense. Methods: We analyzed the role of urinary RBP and of serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk of dialysis. doubling of serum creatinine or death (primary outcome. PO) in 56 type 2 diabetic patients with macroalbuminuric DN. Results: Mean follow-up time was 30.7 +/- 10 months. Urinary RBP and MCP-1 were significantly higher in patients presenting the PO, whereas no difference was shown for TGF-beta or VEGF. In the Cox regression, urinary RBP. MCP-1 and VEGF were positively associated and serum VEGF was inversely related to the risk of the PO. However, after adjustments for creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6; 95% CI 2.7-49.2, p = 0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6-76.4, p = 0.02 for log MCP-1) remained as significant independent predictors of the PO. Conclusion: Urinary RBP and MCP-1 are independently related to the risk of CKD progression in patients with macroalbuminuric DN. Whether these biomarkers have a role in the setting of normoalbuminuria and microalbuminuria in DN should be further investigated. (C) 2012 Elsevier Inc. All rights reserved.

The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has significant morbidity and mortality as 20-40% of patients progress to end-stage renal disease within 20 years of onset. In order to gain insight into the molecular mechanisms involved in the progression of IgAN, we systematically evaluated renal biopsies from such patients. This showed that the MAPK/ERK signaling pathway was activated in the mesangium of patients presenting with over 1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens of patients with IgAN and modest proteinuria (<1 g/day). ERK activation was not associated with elevated galactose-deficient IgA1 or IgG specific for galactose-deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine secretion and was induced by large-molecular-mass IgA1-containing circulating immune complexes purified from patient sera. Moreover, IgA1-dependent ERK activation required renin-angiotensin system as its blockade was efficient in reducing proteinuria in those patients exhibiting substantial mesangial activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in diagnostic renal biopsies may predict the therapeutic efficacy of renin-angiotensin system blockers in IgAN. Kidney International (2012) 82, 1284-1296; doi:10.1038/ki.2012.192; published online 5 September 2012

Chemical Chaperones Curcumin and 4-Phenylbutyric Acid Improve Secretion of Mutant Factor H R127H by Fibroblasts from a Factor H-Deficient Patient

Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. Patients with FH deficiency have a higher risk for development of infections and kidney diseases because of the uncontrolled activation and subsequent depletion of the central regulatory component C3 of the complement system. In this study, we investigated the consequences of the Arg(127)His mutation in FH (FHR127H) previously described in an FH-deficient patient, on the secretion of this protein by skin fibroblasts in vitro. We observed that, although the patient cells stimulated with IFN-gamma were able to synthesize FHR127H, the mutant protein was largely retained within the endoplasmic reticulum (ER), whereas normal human fibroblasts stimulated with IFN-gamma secrete FH without retention in the ER. Moreover, the retention of FHR127H provoked enlargement of ER cisterns after treatment with IFN-gamma. A similar ER retention was observed in Cos-7 cells expressing the mutant FHR127H protein. Despite this deficiency in secretion, we show that the FHR127H mutant is capable of functioning as a cofactor in the Factor I-mediated cleavage of C3. We then evaluated whether a treatment could increase the secretion of FH, and observed that the patient's fibroblasts treated with the chemical chaperones 4-phenylbutiric acid or curcumin increased the secretion rate of FH. We propose that these chemical chaperones could be used as alternative therapeutic agents to increase FH plasma levels in FH-deficient patients caused by secretion delay of this regulatory protein. The Journal of Immunology, 2012, 189: 3242-3248.

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

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-beta 1, alpha-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-beta 1, alpha-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 alpha-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.

Facial lesions caused by renal osteodystrophy in a patient with chronic renal insufficiency: a case report

PURPOSE: Chronic renal insufficiency (CRI) is the last stage of a chronic renal condition in which the kidney loses its filtration and endocrine functions. Chronic endocrine hypofunction causes generalized damage to the body known as Uremic Syndrome, which affects the central nervous system as well as the cardiovascular, hematologic, dermatologic, ophthalmic, endocrine, respiratory, gastrointestinal and skeletal systems. The present study reports the case of a female patient with CRI who presented facial osteodystrophy of the osteitis fibrosa type, and highlights the main features of this condition. CASE DESCRIPTION: A 24-year old, female, Caucasian patient presented chronic glomerulonephritis recurrence and lost the transplanted kidney five years before, undergoing arteriovenous fistula hemodialysis three times a week. She presented swelling of the left masseter area with a hard consistency on palpation, covered by intact skin, swelling at the bottom of the left atrium, with a hard consistency on palpation, a mucosa-like color and absence of inflammation signs, suggesting expansive bone lesions on the face. These features were compatible with hyperparathyroidism brown tumor and/or osteodystrophy. The CT scan showed expansive bone lesions of heterogeneous appearance on the left jaw, maxilla/nasal floor, and right frontotemporal suture areas. The clinical and histopathological characteristics of the lesion, in association with PHT hormone high serum levels led to renal osteodystrophy diagnosis. The patient was referred to the nephrology services. CONCLUSION: Osteodystrophic bone alterations have a high prevalence in renal disease patients, and the dentist must take these alterations into consideration in bone lesion diagnosis for this specific group of patients.

Funktion des Rezeptors der sekretorischen Phospholipasen A 2 bei der Signaltransduktion in glomerulären Mesangiumzellen und entzündlichen Erkrankungen der Niere

Die sekretorischen Phospholipasen A2 (sPLA2) sind Enzyme, welche die Hydrolyse der Esterbindung an der sn-2-Position von Phospholipiden katalysieren, wodurch freie Fettsäuren, welche als Vorläufermolekül von Eicosanoiden dienen, freiwerden. Außerdem wurde gezeigt, dass sPLA2s auch unabhängig von ihrer katalytischen Aktivität durch die Bindung an einen spezifischen sPLA2-M-Typ-Rezeptor (MTR) intrazelluläre Signalwege, wie z.B. die Induktion von proinflammatorischen Genen, aktivieren können. Deshalb wurden in dieser Arbeit weiterführende Studien zur Aufklärung der Lokalisation und der Signaltransduktion der sPLA2s sowie die Bedeutung des MTR durchgeführt. Als Zellmodell für in-vitro-Studien wurden glomeruläre Mesangiumzellen verwendet, da diese Zellen eine zentrale Rolle bei entzündlichen Nierenerkrankungen, wie z.B. der Glomerulonephritis spielen. Durch Isolierung von Mesangiumzellen aus MTR-knockout-Mäusen (C57BL/6) sollten potentielle Unterschiede in der MTR-vermittelten Signaltransduktion im Vergleich zu Mesangiumzellen isoliert aus (C57BL/6) Wildtyp-Mäusen herausgearbeitet werden. Die Untersuchungen dieser Arbeit zeigen, dass verschiedene sPLA2-Enzyme in Maus-Mesangiumzellen exprimiert werden und diese an der konstitutiven Biosynthese von Prostaglandinen beteiligt sind. Der spezifische M-Typ-Rezeptor wird in diesen Zellen im Gegensatz zu Ratten-Mesangiumzellen weder unter physiologischen noch unter proinflammatorischen Bedingungen exprimiert und spielt daher vermutlich keine Rolle bei der Signaltransduktion durch sPLA2s.