ABSTRACT For patients with end stage renal disease, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, waiting times have traditionally been long and options limited. We present the case of a 34-year-old hypersensitized female who underwent renal retransplantation. Histocompatibility tests revealed a calculated panel-reactive antibody of 99.53% with multiple antibodies against class I and II human leucocyte antigens and an eplet analysis was performed. The donor’s potential unacceptable antigens were re-defined and the calculated panel-reactive antibody decreased to 88.38%. After one month the patient received a deceased-donor kidney transplant. Complement dependent cytotoxicity crossmatch was negative; virtual crossmatch and flow cytometry crossmatch with historical serum were positive. High-dose intravenous immunoglobulin and rituximab were added to the thymoglobulin-based induction immunosuppression. Three donor-specific antibodies were detected and plasmapheresis was performed. Renal allograft biopsy revealed no manifestations of rejection. Repeated testing observed a decrease in donor-specific antibodies median fluorescence intensity values. Four months post-transplant, the patient remained with normal graft function without proteinuria. She is receiving a standard maintenance immunosuppression regime with prednisolone, mycophenolate mofetil and tacrolimus. The careful discussion among the transplantation center and histocompatibility laboratory in association with intense immunosuppression and close laboratory monitoring allowed a successful human leukocyte antigen-incompatible deceased donor kidney transplantation in the most critical phase for the occurrence of humoral rejection. It is noteworthy that the new histocompatibility and immunogenetics methodologies provide a more affirmative and comprehensive assessment of mismatch acceptability.

ABSTRACT Operational tolerance in kidney transplantation is characterized by stable serum creatinine < 1.7 mg/dL and proteinuria < 1 g/day in the absence of immunosuppression or immunodeficiency for over one year. However, simultaneous donor specific antibodies are common and serum creatinine is a poor surrogate of early lesions. Consequently, subclinical rejections will meet operational tolerance criteria if sérum creatinine remains stable. We report a patient with operational tolerance criteria followed by biopsy-proven chronic active antibody mediated rejection, discussing the intricate challenges of immunosuppression management.

ABSTRACT Nephrotic syndrome in systemic lupus erythematosus patients with histological evidence of minimal change disease, mesangial proliferation or focal and segmental glomerulosclerosis on light microscopy, represents a distinct clinical entity - lupus podocytopathy. This entity is characterized by a diffuse foot process effacement on electron microscopy and by absence of subepithelial or subendothelial immune‑complex deposition. We report the case of a 49‑year‑old woman admitted on suspicion of lupus nephritis flare, characterized by nephrotic syndrome and acute kidney injury, whose renal biopsy revealed histological features of lupus podocytopathy. Six months after discharge, under prednisolone and azathioprine, she presented 300 mg/day proteinuria, normal kidney function, without hematuria. A review of the pathogenesis, clinical features, diagnostic criteria, treatment and prognosis of lupus podocytopathy is provided. This case highlights the mounting evidence that lupus podocytopathy encompasses distinct clinical and morphological features, that should be included in the upcoming pathological classification of lupus nephritis.

RESUMO Objetivo: Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica. Métodos: Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção. Resultados: Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p < 0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção. Conclusão: A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.

Abstract Objective: To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness. Methods: A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection. Results: Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m. Conclusion: Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.

IgA Nephropathy (IgAN) is the most prevalent biopsy-proven primary glomerular disease worldwide. Historically, thrombotic microangiopathy (TMA) was associated with IgAN in cases of severe hypertension or advanced chronic kidney disease, but recent data suggest that complement activation plays a crucial role in the development of TMA in IgAN. We report a case of Crescentic IgAN with complement-mediated TMA (C-TMA) in a 27-year old male patient with a pathological missense mutation in heterozygosity in the CFH gene and a rare variant in the C3 gene, treated with steroids, cyclophosphamide and plasmapheresis without recovery of kidney function. We also discuss other treatment possibilities and kidney transplant options. Additionally, we will review the latest advances that are enhancing our understanding of the association between IgAN and TMA

Hyperoxaluria is an important complication of short bowel syndrome (SBS) and a non-negligible cause of chronic kidney disease (CKD). We describe the case of a 56-year-old woman with polyarteritis nodosa (PAN) and SBS who was admitted for acute kidney injury (AKI) 2 months after a successful deceased donor kidney transplantation. The diagnostic investigation was consistent with the diagnosis of oxalate nephropathy (OxN) and a set of lifestyle and therapeutic measures was implemented aiming at the reduction of intestinal oxalates absorption. Despite the short-term benefit of this strategy, a progressive and inexorable deterioration of renal function was observed. In this report, we discuss the limited therapeutic options, the ominous prognosis and the risk of recurrence of this rare entity after renal transplantation. Additionally, we reflect on the value of patient compliance in the successful management of the disease and review potential new strategies that may improve the clinical course of this entity in the future

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE), usually developing early in the course of the disease. Almost all patients with lupus nephritis present with positive ANA and anti-dsDNA, Hypocomplementaemia and renal manifestations (haematuria, proteinuria and/or renal failure). However, in a small number of patients, the initial presentation is lupus nephritis with absent serology or clinical features of systemic lupus erythematosus

Introdução: O transplante renal em adultos com alterações congénitas do trato urinário inferior (ACTUI) apresenta complicações específicas. O estudo urológico de bexigas com baixa capacidade e pouco complacentes pode determinar a necessidade de cirurgia vesical reconstrutiva e soluções derivativas. Além disso, esta população apresenta maior risco de infeções do trato urinário (ITUs). Objetivo: Caraterizar os doentes com ACTUI seguidos na Unidade de Transplante Renal do Centro Hospitalar de São João e avaliar complicações pós -transplante renal. Os doentes com refluxo vesicoureteral (RVU) primário foram excluídos da análise. Materiais e Métodos: Foram avaliados 8 doentes com ACTUI com idades entre 13 e 39 anos. A doença renal crónica estabeleceu -se por RVU secundário e ITUs de repetição em contexto de mielomeningocelo (3 casos), válvulas da uretra posterior (1 caso), bexiga neurogénica com ânus imperfurado (1 caso), megaureter congénito (2 casos) e bexiga neurogénica idiopática com dissenergia vesicoesfincteriana (1 caso). Resultados: Todos os doentes foram submetidos a intervenções cirúrgicas antes do transplante: nefrectomia dos rins nativos (2 casos), ablação das válvulas da uretra posterior (1 caso), cistoplastia de aumento (6 casos) e ureteroileostomia (1 caso). Sete doentes mantiveram-se continentes, 6 praticando auto-algaliação intermitente para esvaziamento vesical e 1 usando a manobra de Valsalva. Verificou-se uma taxa de pielonefrites agudas do enxerto renal com necessidade de internamento de 31 episódios por 100 doentes -ano, bastante superior à descrita para transplantados renais por qualquer causa, apesar da sobrevida do enxerto não ter sido afetada. Após um seguimento médio de 104 ± 11.8 meses, 5 doentes mantêm enxertos funcionantes com creatinina sérica média de 1.17 ± 0.40 mg/dl. Conclusão: O transplante renal em doentes com ACTUI apresenta bons resultados após cirurgia prévia para correção das alterações urológicas, apesar da frequência elevada de pielonefrites do enxerto

Introduction: Renal transplantation in adults with congenital abnormalities of the lower urinary tract (CALUT) carries particular complications. Careful urologic evaluation of abnormal bladders, due to neuropathy or outlet obstruction, may indicate the need for surgical correction before transplantation. This population is also at increased risk for urinary tract infections. Purpose: We assessed the outcome of renal transplantation in patients with CALUT at our Transplant Unit. Patients with primary vesicoureteral reflux (VUR) were excluded from our analysis. Materials and Methods: A total of eight patients with CALUT, 13 to 39 years old, were evaluated. End -stage renal disease was caused by secondary VUR and recurrent urinary tract infections in patients with myelomeningocele (three cases), posterior urethral valves (one case), neurogenic bladder associated with imperforate anus (one case), congenital megaureter (two cases) and idiopathic neuropathic bladder and sphincter dyssynergia (one case). Results: All patients underwent surgical interventions before transplantation: ureteronephrectomy of the native kidneys (two cases), ablation of posterior urethral valves (one case), augmentation cystoplasty (six cases) and construction of an ileal conduit (one case). Seven patients remained continent, six were able to empty the bladder by clean intermittent selfcatheterization and the remaining by using the Valsalva maneuver. A rate of 31 episodes per 100 patient-years of graft pyelonephritis was found, much higher when compared to other transplant recipients, although graft survival was not affected. After a mean follow -up of 104 ± 11.8 months, five patients have kept functioning grafts with mean serum creatinine of 1.17 ± 0.40 mg/dl. Conclusion: Renal transplant in patients with CALUT has good outcomes after preparatory urologic surgical corrections although graft pyelonephritis remains a frequent complication

As amiloidoses são um grupo heterogéneo de doenças classificadas de acordo com a composição das suas proteínas amiloidogénicas. Frequentemente, os tecidos preservados em parafina são usados para identificação imunohistoquímica. A análise de ADN deve ser sempre considerada se houver suspeita de amiloidose hereditária. Dado que os rins são um dos órgãos mais frequentemente envolvidos nas amiloidoses sistémicas, procedemos à classificação imunohistoquímica de 102 casos consecutivos de doença amiloide confirmada por biópsia renal. A análise de ADN foi realizada para confirmar o diagnóstico de amiloidose hereditária. As características demográficas, doença subjacente e dados clínicos à data da biópsia foram obtidos pela revisão retrospetiva dos registos médicos. O tipo de amiloidose obtido por identificação imunohistoquímica foi AA em 60 (58,8%) doentes, AL em 21 (20,6%), AFib em quatro (3,9%), ATTR em dois (2,0%), AApoAI em um (2,0%), ALys em um (2,0%), e em um (2,0%) coexistiam os tipos AL e AA. Em 12 (11,7%) não foi identificado o tipo de amiloide: oito (7,8%) por imunohistoquímica negativa e quatro (3,9%) devido a amostra insuficiente. A análise de ADN confirmou os casos AFib e ATTR pela identificação das mutações pontuais FGA p.Glu545Val e TTR p.Met51Val, respetivamente. A média de idade à data do diagnóstico foi 53,3 anos (49,4 para AA, 63,0 para AL e 53,9 para AFib). As infeções crónicas foram a principal causa de amiloidose AA, sobretudo a tuberculose, e foi apenas identificada uma AA familiar associada a síndrome de Muckle-Wells. A síndrome nefrótica foi a manifestação clínica mais frequente, independentemente do tipo de amiloide. Na nossa série, a amiloidose AA continua a ser a amiloidose sistémica mais frequente. Seis doentes tiveram amiloidose hereditária inequívoca. A imunohistoquímica não identificou a proteína precursora em quase 8% dos doentes; contudo, a utilização de um painel de anticorpos mais alargado poderá melhorar o diagnóstico.

Amyloidoses are a group of heterogeneous diseases classified according to the nature of their causative amyloid proteins. Commonly, paraffin-embedded tissue is used for the typing of amyloid by immunohistochemistry. DNA analysis should always be considered if hereditary amyloidosis is suspected. Since the kidneys are one of the organs that are most commonly involved in amyloid deposition in systemic amyloidoses, we screened 102 consecutive cases with biopsy-proven amyloid disease by immunohistochemistry. DNA analysis was performed to confirm a diagnosis of hereditary amyloidosis. Demographic characteristics, underlying disease and clinical data at the time of renal biopsy were obtained by retrospective review of medical records. The amyloidosis type according to immunohistochemical amyloid protein identification was AA in 60 (58.8%) patients, AL in 21 (20.6%), AFib in four (3.9%), ATTR in two (2.0%), AApoAI in one (1.0%), ALys in one (1.0%) and combined AL and AA in one (1.0%). The type of protein could not be classified in 12 (11.7%) patients: eight (7.8%) because of negative immunohistochemistry and four (3.9%) due to the lack of adequate tissue. DNA analysis confirmed AFib and ATTR cases by the identification of the point mutations FGA p.Glu545Val and TTR p.Met51Val, respectively. Mean age at diagnosis was 53.3 years (49.4 for AA, 63.0 for AL and 53.9 for AFib). Chronic infections were the most frequent disorder associated with AA amyloidosis, mainly tuberculosis, and only one patient had familial AA associated with Muckle-Wells syndrome. Nephrotic syndrome was the most frequent clinical manifestation, independently of the amyloid type. In our series, AA amyloidosis is still the most frequent type of systemic amyloidoses. Six patients had unequivocal hereditary amyloidosis. Immunohistochemistry did not establish the precursor protein in almost 8% of patients; however, an improvement could be obtained using a wider panel of amyloid antibodies.

A sarcoidose e uma doença inflamatória cronica, de atingimento multissistemico, cuja etiologia permanece ainda por identificar. Caracteriza-se, do ponto de vista histopatológico, pela formação de granulomas não caseosos em qualquer órgão envolvido. Os mecanismos mais frequentemente implicados na disfunção renal devem-se aos distúrbios no metabolismo do cálcio; mais raramente podem ocorrer nefrite intersticial granulomatosa e doença glomerular. Os autores apresentam três casos de nefrite intersticial com o achado de insuficiência renal como manifestação inaugural de sarcoidose. Foi efectuado tratamento com prednisolona na dose de 1 mg/Kg/dia, verificando-se recuperação parcial e sustentada da função renal.

Sarcoidosis is a chronic inflammatory disorder of unknown cause. The histopathological feature is the presence of the non-caseating granuloma in any organ involved. The mechanisms most frequently implicated in renal dysfunction are due to disturbances in calcium metabolism; more rarely, granulomatous interstitial nephritis and glomerular disease may occur. The authors report three cases of sarcoidosis presented as interstitial nephritis with renal failure. Prednisolone treatment was performed at a dose of 1 mg/kg/day with partial and sustained recovery of renal function.