Pilosidade Púbica na Criança e Hiperplasia Congénita Supra-Renal Não Clássica

Antes dos 8 anos de idade no sexo feminino e dos 9 no masculino, o aparecimento de pelos púbicos, pode ser a primeira manifestação de doença das gónadas ou das supra-renais. Para reconhecimento da Hiperplasia congénita supra-renal de início tardio, em situações de Pubarca prematura, realizámos a Prova curta de estimulação da supra-renal com Synacthen, em trinta crianças. Cinco meninas e um rapaz revelaram um défice de 21-hidroxilase, demonstrado pelo valores da 17-OH Progesterona sérica aos 60 minutos;28,8 +_ 15,2ng/ml, sendo num grupo de controle 2,30 ng/ml (p<0,01). A incidência de 20% encontrada, justifica a realização desta prova em todas as Pubarcas prematuras.

Orthotopic Liver Transplantation in Familial Amyloidotic Polyneuropathy Is Associated with Long-Term Progression of Renal Disease

Orthotopic liver transplantation has become the treatment of choice for familial amyloidotic polyneuropathy. The aims of this study were to evaluate the renal complications post orthotopic liver transplantation in familial amyloidotic polyneuropathy and their impact. We retrospectively studied 185 recipients who underwent 217 orthotopic liver transplants. Mean age 36.8±9.5 years, 59% males, 14.3% with renal dysfunction pre orthotopic liver transplantation. Mean follow-up 3.6±3.7 years. Thirty-two patients died. Univariate and multivariate analysis were performed, and p<0.05 was considered significant. Acute kidney injury occurred in 57 patients and renal replacement therapy was needed in 16/57. In multivariate analysis, acute kidney injury was correlated with development of chronic kidney disease (p<0.001). Relating to development of chronic kidney disease, 23.5% had progress to stage 3, 6% to stage 4 and 5.1% to stage 5d. According to Spearmen correlation, risk factors for chronic kidney disease development were age (p<0.001), renal dysfunction pre orthotopic liver transplantation (p<0.001) and acute kidney injury post orthotopic liver transplantation (p<0.001). Mortality was correlated with age (p<0.001), retransplantation need (p=0.004), renal dysfunction pre orthotopic liver transplantation (p<0.001), acute kidney injury post orthotopic liver transplantation (p=0.04), and chronic kidney disease stage 5 (p<0.001). Using binary regression, mortality was correlated with chronic kidney disease development (p=0.02). In conclusion, familial amyloidotic polyneuropathy patients are disposed to renal complications that have a negative impact on the survival of these patients.

Diagnóstico Pré-Natal de Uropatia: Importância do Desenvolvimento Embriológico Renal

As uropatias malformativas constituem a principalcausa de anomalia neonatal nao letal. Estas anomalias do desenvolvimento devem ser interpretadas com base no conhecimento da morbilidade e, em alguns casos, a mortalidade associada a este tipo de patologia 1,2. As malformações congénitas devem ser pensadas com base no conhecimento da dinâmica do normal desenvolvimento embrionário e dos múltiplos factores reguladores intervenientes, so assim será possivel estabelecer estratégias eficazes de investigação e terapêutica.

The 2009 Pandemic Influenza A (H1N1) Infection: Renal Histopathology Findings in Two Infected Patients

Background: Acute kidney injury in the pandemic swine origin influenza A virus (H1N1) infection has been reported as coursing with severe illness, although renal pathogenic mechanisms and histologic features are still being characterised. Case Report: We present two patients admitted with H1N1 pneumonia, sepsis, acute respiratory distress syndrome and need for invasive mechanical ventilation who developed acute kidney injury and became dialysis-dependent. In both cases a kidney biopsy was performed to establish a definitive diagnosis. Severe acute tubular necrosis was identified, with no further abnormalities. Conclusion: This report seems to confirm that the acute kidney injury in H1N1 infection is focused on the tubular cells. Our cases corroborate the renal histopathologic findings of other studies, highlighting the central role of the tubular cell. We bring new evidence of the histopathology of AKI in H1N1 infection since our data were collected in living patients and not via post-mortem studies.

Renal Pathology in Portuguese HIV-Infected Patients

HIV-infected patients may be affected by a variety of renal disorders. Portugal has a high incidence of HIV2 infection and a low prevalence of HIV-infected patients under dialysis treatment. The aim of this study was to characterise the type of renal disease in Portuguese HIV-infected patients and to determine if HIV2 infection is associated to renal pathology. Only 60 of the 5158 HIV-infected patients followed in our hospital underwent renal biopsy. Clinical and laboratory data and the type of renal disease were reviewed. Male gender was predominant (76.7%), as was Caucasian race (78.3%). Mean age was 37.9±10.6 years. The majority had criteria for AIDS, 66% were on combined antiretroviral therapy and 18.3% were on dialysis. The predominant lesions were immunecomplex glomerulonephritis (n=19), tubulointerstitial nephropathy (n=12), focal segmental glomerulosclerosis(n=11), followed by HIVAN (n=8). Other patterns(amyloidosis, vasculitis, minimal change lesion) were observed. Only three patients were HIV2 infected, and presented diabetic nephropathy, acute tubular necrosis and tubulointerstitial nephritis. No correlations between clinical findings and renal pathology were found. In conclusion, renal disease in HIV patients has a broad spectrum, and renal biopsy remains the gold standard for establishing the diagnosis and guide treatment. Renal disease is not frequent in HIV2-infected patients, and, when present, is probably not directly associated with HIV infection.

Impact of Renal Dysfunction on Liver Transplantation: a Retrospective Study in 708 Orthotopic Liver Transplant Recipients

Renal dysfunction often complicates the course of orthotopic liver transplant recipients and is associated with increased morbid -mortality. The aims of this study were to determine the incidence of chronic renal disease and its impact on patient survival. Clinical data included age, gender and weight,aetiology of hepatic failure, presence of diabetes,hypertension, hepatitis B and C infection, renal dysfunction pretransplant and immunosuppression. Laboratory data included serum creatinine at days 1, 7, 21, month 6, 12 and yearly. The glomerular filtration rate was determined by Cockcroft-Gault equation. We studied retrospectively from September 1992 to March 2007 708 orthotopic liver transplant recipients. Mean age 44±12.6 years, 64% males, 17% diabetic, 18.8% hypertensive, 19.9% with hepatitis C and 3.8% hepatitis B. Renal dysfunction pretransplant was known in 21.6%. Mean follow-up was 3.6 years. Mean transplant survival 75% at 12 months. 154 patients died. Univariate and multivariate analyses were performed and a p<0.05 was considered significant. Acute kidney injury occurred in 33.2%. Chronic kidney disease stage 3 was observed in 34.3%,stage 4 in 6.2% and stage 5 in 5.1%. At the time of this study, 46.4% were on Cyclosporine A, 44.7% on tacrolimus and 8.9% on sirolimus. Using multivariate analysis, renal dysfunction was correlated with renal dysfunction pre -orthotopic liver transplant (p<0.001), acute kidney injury (p<0.001), haemodialysis development (p<0.001), and inversely correlated with the use of mycophenolate mophetil (p<0.001); mortality was positively correlated with renal dysfunction pretransplant (p=0.03),chronic kidney disease stage 4 (p=0.001), chronic kidney disease stage 5 (p<0.001) and inversely correlated with the use of tacrolimus (p=0.006). In conclusion orthotopic liver transplant recipients are disposed to renal complications that have a negative impact on survival of these patients.

De Novo Hypertension and Decline of Renal Function in a Young Woman with Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Antiphospholipid syndrome nephropathy and lupus nephritis have similar clinical and laboratory manifestations and achieving the accuracy of diagnosis required for correct treatment frequently necessitates a kidney biopsy. We report the case of a 29-year-old woman referred to the nephrology service for de novo hypertension, decline of renal function and proteinuria. She had had systemic lupus erythematosus and antiphospholipid syndrome since the age of 21 and was taking oral anticoagulation. Two weeks later, after treatment of hypertension and achievement of adequate coagulation parameters, a percutaneous renal biopsy was performed. The biopsy revealed chronic lesions of focal cortical atrophy, arterial fibrous intimal hyperplasia and arterial thromboses, which are typical features of antiphospholipid syndrome nephropathy. We describe the clinical manifestations and histopathology of antiphospholipid syndrome nephropathy and review the literature on renal biopsy in patients receiving anticoagulation.

Diabetes Mellitus and Renal Disease: When to Perform a Renal Biopsy?

Background: Several studies suggest that nondiabetic renal disease (NDRD) is common in patients with diabetes mellitus. The aim of this analysis of renal biopsies in diabetic patients was (a) to assess the prevalence and type of NDRD and (b) to identify its clinical and laboratory predictors. Methods: This retrospective study analysed clinical and laboratory data and biopsy findings in diabetic patients observed by a single pathologist over the past 25 years. Based on biopsy findings, patients were categorised as (i) isolated diabetic nephropathy,(ii) isolated NDRD and (iii) NDRD superimposed on diabetic nephropathy. Results: Of the 236 patients studied, 60% were male and the mean age was 56.3 (±14.2) years. Of these, 91% had known diabetes mellitus at the time of biopsy (13% type 1 and 87% type 2). Isolated diabetic nephropathy was found in 125 (53%), isolated NDRD in 89 (38%) and NDRD superimposed on diabetic nephropathy in 22 (9%) patients. The main indication for biopsy in the three groups was nephrotic proteinuria. Patients with isolated NDRD and NDRD superimposed on diabetic nephropathy presented acute deterioration of renal function more frequently (p<0.001) and had more microhaematuria(p<0.001) as indications for renal biopsy. Focal segmental glomerulosclerosis and membranous nephropathy were the most frequent diagnoses in patients with NDRD. Patients with isolated diabetic nephropathy were younger (p=0.02), presented a longer duration of diabetes mellitus (p<0.001) and had more frequent retinopathy (p<0.001). The prevalence of microhaematuria was higher in patients with isolated or superimposed NDRD (p=0.01). Conclusion: The prevalence of NDRD (either isolated or superimposed on diabetes mellitus) is remarkably frequent in diabetic patients in whom nephrologists consider renal biopsy an appropriate measure. Predictors of NDRD were older age, shorter duration of diabetes mellitus, absence of retinopathy and presence of microhaematuria.

Leflunomide and Polyomavirus-Associated Nephropathy in Renal Transplant

Polyomavirus nephropathy is a major complication in renal transplantation, associated with renal allograft loss in 14 to 80% of cases. There is no established treatment, although improvement has been reported with a variety of approaches. The authors report two cases of polyomavirus infection in renal allograft recipients. In the first case, a stable patient presented with deterioration of renal function, worsening hypertension and weight gain following removal of ureteral stent placed routinely at the time of surgery. Ultrasound examination and radiology studies revealed hydronephrosis due to ureteral stenosis. A new ureteral stent was placed, but renal function did not improve. Urinary cytology revealed the presence of decoy cells and polyomavirus was detected in blood and urine by qualitative polymerase chain reaction. Renal biopsy findings were consistent with polyomavirus -associated nephropathy. In the second case, leucopaenia was detected in an asymptomatic patient 6 months after transplantation. Mycophenolate mophetil dosage was reduced but renal allograft function deteriorated, and a kidney biopsy revealed polyomavirus -associated nephropathy, also with SV40 positive cells. In both patients immunosuppression with tacrolimus was reduced, mycophenolate mophetil stopped and intravenous immune globulin plus ciprofloxacin started. As renal function continued to deteriorate, therapy with leflunomide (40 mg/day) was associated and maintained during 5 and 3 months respectively. In the first patient, renal function stabilised within one month of starting leflunomide and polymerase chain reaction was negative for polyomavirus after 5 months. A repeated allograft biopsy 6 months later showed no evidence of polyomavirus nephropathy. In the second patient, polyomavirus was undetectable in blood and urine by polymerase chain reaction after 3 months of leflunomide treatment, with no evidence of polyomavirus infection in a repeated biopsy 6 months after beginning treatment.

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%).

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.