506 research outputs found
Clinical and Pathological Findings in Women with Fabry Disease
Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide
range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive
accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance.
Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies
diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings.
Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated
glomerular filtration rate (CKD EPI equation)
was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and
thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal.
Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in
three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions
were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles.
Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids
is a characteristic histologic finding
of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria
and/or chronic kidney disease, especially if there is a family history of kidney disease
C4d Detection in Renal Allograft Biopsies: Immunohistochemistry vs. Immunofluorescence
Introduction. Peritubular capillary complement 4d staining is one of the criteria for the diagnosis of antibody-mediated rejection, and research into this
is essential to kidney allograft evaluation. The immunofluorescence technique applied to frozen sections is the present gold-standard method for complement 4d staining and is used routinely in our laboratory.
The immunohistochemistry technique applied to
paraffin-embedded tissue may be used when no
frozen tissue is available.
Material and Methods. The aim of this study is to evaluate the sensitivity and specificity of immunohistochemistry
compared with immunofluorescence. We
describe the advantages and disadvantages of the immunohistochemistry vs. the immunofluorescence technique. For this purpose complement 4d staining was performed retrospectively by the two methods in indication biopsies (n=143) and graded using the Banff 07 classification.
Results. There was total classification agreement between methods in 87.4% (125/143) of cases. However, immunohistochemistry staining caused more difficulties in interpretation, due to nonspecific staining
in tubular cells and surrounding interstitium. All cases negative by immunofluorescence were also negative by immunohistochemistry. The biopsies were classified as positive in 44.7% (64/143) of cases performed by immunofluorescence vs. 36.4% (52/143) performed by immunohistochemistry. Fewer biopsies were classified as positive diffuse in the immunohistochemistry group(25.1% vs. 31.4%) and more as positive focal (13.2% vs. 11.1%). More cases were classified as negative by immunohistochemistry (63.6% vs. 55.2%). Study by ROC curve showed immunohistochemistry has a specificity
of 100% and a sensitivity of 81.2% in relation to immunofluorescence (AUC: 0.906; 95% confidence interval: 0.846-0.949; p=0.0001).
Conclusions. The immunohistochemistry method
presents an excellent specificity but lower sensitivity to C4d detection in allograft dysfunction. The evaluation is more difficult, requiring a more experienced
observer than the immunofluorescence method.
Based on these results, we conclude that the immunohistochemistry technique can safely be used when immunofluorescence is not available
Zero-Time Kidney Histology Predicts Early Graft Function
Our purposes are to determine the impact of histological factors observed in zero-time
biopsies on early post transplant kidney allograft function. We specifically want to compare the semi-quantitative Banff Classification of zero time biopsies with quantification of % cortical area fibrosis.
Sixty three zero-time deceased donor allograft biopsies were retrospectively semiquantitatively scored using Banff classification. By adding the individual chronic parameters a Banff Chronic Sum (BCS) Score was generated. Percentage of cortical area Picro Sirius Red (%PSR) staining was assessed and calculated with a computer program.
A negative linear regression between %PSR/ GFR at 3 year post-transplantation was
established (Y=62.08 +-4.6412X; p=0.022). A significant negative correlation between
arteriolar hyalinosis (rho=-0.375; p=0.005), chronic interstitial (rho=0.296; p=0.02) ,
chronic tubular ( rho=0.276; p=0.04) , chronic vascular (rho= -0.360;P=0.007), BCS (rho=-0.413; p=0.002) and GFR at 3 years were found. However, no correlation was found
between % PSR, Ci, Ct or BCS.
In multivariate linear regression the negative predictive factors of 3 years GFR were: BCS in histological model; donor kidney age, recipient age and black race in clinical model. The BCS seems a good and easy to perform tool, available to every pathologist, with significant predictive short-term value. The %PSR predicts short term kidney function in univariate study and involves extra-routine and expensive-time work. We think that %PSR must be regarded as a research instrument
C4d Presence in Kidney Allograft Biopsy: Sensitivity and Specifity of Immunoperoxidase vs Immunofluorescence
OBJECTIVES:
Evaluate the sensitivity/specificity of immunoperoxidase method in comparison with the standard immunofluorescence.
MATERIAL AND METHODS:
Retrospective review of 87 biopsies made for allograft dysfunction. Immunofluorescence (IF) was performed in frozen allograft biopsies using monoclonal antibody anti-C4d from Quidel®. The indirect immunoperoxidase (IP) technique was performed in paraffin-embebbed tissue with polyclonal antiserum from Serotec®. Biopsies were independently evaluated by two nephropathologist according Banff 2007 classification.
RESULTS:
By IF, peritubular C4d deposition were detected in 60 biopsies and absent in 27 biopsies. The evaluation of biopsy by IP was less precise due to the presence of background and unspecific staining.
We find 13.8% (12/87) of false negative and Banff classification concordance in 79.3% (69/87) of cases (table1).
The ROC curve study reveal a specificity of 100% and sensitivity of 80.0 % of IP method in relation to the gold standard (area under curve:0.900; 95% Confidence interval :0.817-0.954; p=0.0001).
Banff Classification C4d Cases
Immunofluorescence Immunoperoxidase n =87
Diffuse Negative 3 (3.4%)
Focal Negative 9 (10.3%)
Negative Negative 27 (31.0%)
Diffuse Diffuse 33 (37.9%)
Focal Focal 9 (10.3%)
Diffuse Focal 6 (6.9%)
CONCLUSION:
The IP method presents a good specificity, but lesser sensitivity to C4d detection in allograft dysfunction. The evaluation is more difficult, requiring more experience of the observer than IF method. If frozen tissue is unavailable, the use of IP for C4d detection is acceptable
Amiloidose. Caracterização Epidemiológica, ClÃnica e Morfológica
Introdução: A amiloidose é uma doença sistémica, cujo diagnóstico cabe
frequentemente ao nefrologista. O tipo de amiloidose varia de acordo com o grau de desenvolvimento do paÃs, com maior prevalência de amiloidose AL nos paÃses
ricos.
Material e métodos: Revisão retrospectiva de todas as biopsias de rim nativo
avaliadas no serviço entre 1981 e 2008. Caracterização clÃnica dos doentes à data da
biópsia. Avaliação morfológica qualitativa do tipo de substância amiloÃde por
imunofluorescência e imunoperoxidase. Avaliação semi-quantitativa do grau de
depósitos de acordo com a sua localização; grau de glomeruloesclerose e fibrose tubulo -interstical. Resultados: Neste perÃodo de 28 anos, observámos 202 biópsias positivas para substância amiloÃde (3,5% de 5797) num total de 197 doentes (54,4% homens vs 45,5 mulheres), com idade mediana de 59,5 ± 15,6
anos. A maioria (68%) dos doentes foi biopsada por sÃndrome nefrótico. A
insuficiência renal e as alterações assintomáticas urinárias foram os outros
principais motivos de biopsia em 15 % e 7% dos casos, respectivamente. Os doentes na altura da biopsia apresentavam proteinúria mediana de 5 g/dia ± 5,4 (n=144) e
creatinina mediana de 1,3 ± 1,7 mg/dl (n=150). As amiloidoses foram classificadas
como AA em 51% dos casos, AL em 31,6% (25,5% lambda e 5,9% kappa) e Polineuropatia Amiloidótica Familiar em 3,5%. Não foi possÃvel a caracterização do tipo de amilóide, por dificuldade técnica, em 12,8% das biópsias. A amiloidose revelou-se a terceira causa de sÃndrome nefrótico nos doentes com mais de 65 anos. Os doentes com amiloidose primária são significativamente mais velhos do que aqueles com amiloidose secundária ou PAF (65,2 vs 53,7 vs 52,7
respectivamente, p <0,05).Verificámos uma diminuição da incidência das amiloidoses AA com aumento das AL, com inversão do predomÃnio das AA em relação as AL a partir de 1995. Em termos morfológicos, a maioria das biópsias caracteriza-se por deposição marcada de amilóide no glomérulo (30% com +++) e nos vasos (40% com +++), com escassa deposição a nÃvel intersticial cortical (60%
sem depósitos) e medular (50% sem depósitos). Estudámos as possÃveis
relações entre manifestações clÃnicas e morfologia renal. Verificámos uma
correlação positiva entre creatinina e grau de fibrose e/ou grau de deposição
intersticial. Não encontrámos relação entre proteinúria e grau/local de deposição de amilóide. Conclusões: Actualmente, em Portugal, predomina a amiloidose AL, que surge em doentes mais idosos e se manifesta
mais frequentemente por sindrome nefrótico. A função renal a data da biópsia correlaciona-se com o grau de fibrose tubulo-interstical renal
Doença Ateroembólica Como Causa de Disfunção Primária do Enxerto Renal
Atheroembolic renal disease, also referred to as cholesterol crystal embolization, is a rare cause of renal failure, secondary to occlusion of renal arteries, renal arterioles and glomerular capillaries with cholesterol
crystals, originating from atheromatous plaques of the aorta and other major arteries. This disease can occur very rarely in kidney allografts in an early or a late clinical form.
Renal biopsy seems to be a reliable diagnostic test and cholesterol clefts are the pathognomonic finding. However, the renal biopsy has some limitations as the typical lesion is focal and can be easily missed in
a biopsy fragment.
The clinical course of these patients varies from complete recovery of the renal function to permanent graft loss. Statins, acetylsalicyclic acid, and corticosteroids have been used to improve the prognosis.
We report a case of primary allograft dysfunction caused by an early and massive atheroembolic renal disease. Distinctive histology is presented in several consecutive biopsies. We evaluated all the cases of
our Unit and briefly reviewed the literature.
Atheroembolic renal disease is a rare cause of allograft primary non -function but may become more prevalent as acceptance of aged donors and recipients for transplantation has become more frequent
Peritubular Capillaries C4d Deposits in Renal Allograft Biopsies and Anti HLA I/II Alloantibodies Screening. Incidence and Clinical Importance
Aim: To characterise clinically the patients with C4d in peritubular capillaries deposits (C4dPTCD) and/or circulating anti-HLA class I/II alloantibodies. To determine the correlation between positive C4dPTCD and
circulating anti-HLA class I/II alloantibodies during episodes of graft dysfunction.
Subjects and Methods: C4d staining was performed in biopsies with available frozen tissue obtained between January 2004 and December 2006. The study was prospective from March 2005, when a serum sample
was obtained at the time of biopsy to detect circulating anti-HLA class I/II alloantibodies.
Results: We studied 109 biopsies in 86 cadaver renal transplant patients. Sixteen of these (14.7%) presented diffuse positive C4dPTCD. There was a 13.5% rate of +C4dPTCD incidence within the first six months of
transplantation and 16% after six months (p>0.05). Half of the +C4dPTCD in the first six months was associated with acute humoral rejection. After six months, the majority of +C4dPTCD (n=7/8) was present in biopsies
with evidence of interstitial fibrosis/tubular atrophy and/or transplant glomerulopathy. The C4dPTCD was more frequent in patients with positive anti-HCV antibodies(p<0.0001), a previous renal transplant (p=0.007), and with a panel reactivity antibody (PRA) ≥ 50%(p=0.0098). The anti-HCV+ patients had longer time on dialysis (p=0.0019) and higher PRA(p=0.005). Circulating anti-HLA I/II alloantibodies were screened in 46 serum samples. They were positive in 10.9% of samples, all obtained after six months post transplant. Circulating
alloantibodies were absent in 92.5% of the C4d negative biopsies.
Conclusion: We found an association between the presence of C4dPTCD and 2nd transplant recipients,higher PRA and the presence of anti-HCV antibodies.
The presence of HCV antibodies is not a risk factor for C4dPTCD per se, but appears to reflect longer time on dialysis and presensitisation. In renal dysfunction
a negative alloantibody screening is associated with a reduced risk of C4dPTCD (<10%)
Sex differences in presenting symptoms of acute coronary syndrome: the EPIHeart cohort study
Objectives Prompt diagnosis of acute coronary syndrome (ACS) remains a challenge, with presenting symptoms affecting the diagnosis algorithm and, consequently, management and outcomes. This study aimed to identify sex differences in presenting symptoms of ACS.
Design Data were collected within a prospective cohort study (EPIHeart).
Setting Patients with confirmed diagnosis of type 1 (primary spontaneous) ACS who were consecutively admitted to the Cardiology Department of two tertiary hospitals in Portugal between August 2013 and December 2014.
Participants Presenting symptoms of 873 patients (227 women) were obtained through a face-to-face interview. Outcome measures: Typical pain was defined according to the definition of cardiology societies. Clusters of symptoms other than pain were identified by latent class analysis. Logistic regression was used to quantify differences in presentation of ACS symptoms by sex.
Results Chest pain was reported by 82% of patients, with no differences in frequency or location between sexes. Women were more likely to feel pain with an intensity higher than 8/10 and this association was stronger for patients aged under 65 years (interaction P=0.028). Referred pain was also more likely in women, particularly pain referred to typical and atypical locations simultaneously. The multiple symptoms cluster, which was characterised by a high probability of presenting with all symptoms, was almost fourfold more prevalent in women (3.92, 95% CI 2.21 to 6.98). Presentation with this cluster was associated with a higher 30-day mortality rate adjusted for the GRACE V.2.0 risk score (4.9% vs 0.9% for the two other clusters, P<0.001).
Conclusions While there are no significant differences in the frequency or location of pain between sexes, women are more likely to feel pain of higher intensity and to present with referred pain and symptoms other than pain. Knowledge of these ACS presentation profiles is important for health policy decisions and clinical practice.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT; Portuguese Ministry of Science, Technology and Higher Education) (FCOMP-01-0124-FEDER-028709), under the project ’Inequalities in coronary heart disease management and outcomes in Portugal' (Ref. FCT PTDC/DTP-EPI/0434/2012) and Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013)
Inequalities in access to cardiac rehabilitation after an acute coronary syndrome: the EPiHeart cohort
Objectives To estimate cardiac rehabilitation (CR) referral and participation rates among patients with acute coronary syndrome (ACS) and to identify their determinants, in two Portuguese regions.
Design Prospective cohort study.
Setting Patients consecutively admitted to the cardiology department of two hospitals, one in the district of Porto and one in the north-east region (NER) of Portugal, were enrolled in the EPIHeart cohort and then followed up for 6 months.
Participants Between August 2013 and December 2014, 939 patients were included in the cohort, and 853 were re-evaluated at 6-month follow-up.
Outcome measures Referral rate was defined as the proportion of eligible patients who were referred to a CR programme, whereas participation rate was defined as the proportion of eligible patients who completed a CR programme, as was recommended by their physicians.
Results Patients referred were 32.3% and 10.7% of those eligible in Porto and NER, respectively. In both regions, referral to CR decreased with age and with longer travel times to CR centres and increased with education or social class. At follow-up, 128 patients from Porto (26.2% of those eligible and 81.0% of those referred) and 26 from NER (7.1% of those eligible and 66.7% of those referred) reported actually participating in a CR programme. In Porto, the main barriers to participation were the long time until a programme was available and lack of perceived benefit. Patients in NER identified distance to CR and costs as the main barriers.
Conclusions CR remains clearly underused in Portugal, with major inequalities in access between regions. Achieving equitable and greater use of CR requires a multilevel approach addressing barriers related to healthcare system, providers and patients in order to improve provision, referral and participation.This study was supported by FEDER through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) (FCOMP-01-0124-FEDER-028709), under the project ‘Inequalities in coronary heart disease management and outcomes in Portugal’ (FCT PTDC/DTP-EPI/0434/2012) and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; ref UID/DTP/04750/2013)
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