Coexisting presentation of two rare genetic variants of autosomal dominant polycystic kidney disease and Alport syndrome.

Alport syndrome and autosomal dominant polycystic kidney disease are monogenic causes of chronic kidney disease and end-stage kidney failure. We present a case of a man in his 60s with progressive chronic kidney disease, bilateral sensorineural hearing loss and multiple renal cysts. Genetic analysis revealed a heterozygous variant in COL4A3 (linked to Alport syndrome) and in the GANAB gene (associated with a milder form of autosomal dominant polycystic kidney disease). Although each variant confers a mild risk of developing end-stage kidney disease, the patient presented a pronounced and accelerated progression of chronic kidney disease, which goes beyond what would be predicted by adding up their individual effects. This suggests a potential synergic effect of both variants, which warrants further investigation.

Renal Transplantation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center 10-Year Experience.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease. The optimal timing of kidney transplantation for end-stage renal disease due to AAV and the risk of relapse after kidney are poorly defined. Our study aimed to evaluate the clinical outcomes of AAV after kidney transplantation, namely the risk of relapse, rejection, and oncologic disease. METHODS: This retrospective study included all patients with AAV submitted to a kidney transplant between January 2011 and December 2020. RESULTS: Twenty-seven patients (20 males/7 females; mean age 47 years) received a kidney transplant for end-stage renal disease secondary to microscopic polyangiitis (n = 25) or granulomatosis with polyangiitis (n = 2). All patients were in clinical remission at the time of the kidney transplant, but 11 patients were ANCA-positive. A vasculitis relapse after kidney transplantation occurred in only 1 patient (3.7%). Rejection episodes, proven by allograft biopsy, were present in 3 patients (11.1%), with graft losses in 2 (66.7%). The median time until the graft was lost after the initial rejection diagnosis was 27 ± 8 months. Oncologic complications were present in 9 patients (33.3%). Five patients died (18.5%), and the main cause of death was cardiovascular disease (n = 3, 60.0%), followed by oncologic disease (n = 2, 40.0%). CONCLUSIONS: Kidney transplantation is a safe and effective option for treating end-stage renal disease secondary to AAV. Current immunosuppression regimens make relapses and rejection infrequent but place oncologic complications at a higher incidence.

Charcot-Marie-Tooth disease: from historical landmarks in Brazil to current care perspectives / Doença de Charcot-Marie-Tooth: dos marcos históricos no Brasil até as perspectivas atuais de cuidado

Abstract Hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease (CMT), traditionally refers to a group of genetic disorders in which neuropathy is the main or sole feature. Its prevalence varies according to different populations studied, with an estimate between 1:2,500 to 1:10,000. Since the identification of PMP22 gene duplication on chromosome 17 by Vance et al., in 1989, more than 100 genes have been related to this group of disorders, and we have seen advances in the care of patients, with identification of associated conditions and better supportive treatments, including clinical and surgical interventions. Also, with discoveries in the field of genetics, including RNA interference and gene editing techniques, new treatment perspectives begin to emerge. In the present work, we report the most import landmarks regarding CMT research in Brazil and provide a comprehensive review on topics such as frequency of different genes associated with CMT in our population, prevalence of pain, impact on pregnancy, respiratory features, and development of new therapies.

Resumo A neuropatia sensitivo-motora hereditária, também conhecida como doença de Charcot-Marie-Tooth (CMT), tradicionalmente se refere a um grupo de doenças genéticas em que a neuropatia é a principal ou única manifestação. Sua prevalência varia de acordo com as diferentes populações estudadas, com estimativa entre 1:2.500 a 1:10.000. Desde a identificação da duplicação do gene PMP22 no cromossomo 17, por Vance et al., em 1989, mais de 100 genes foram relacionados a esse grupo de doenças e temos visto avanços no atendimento aos pacientes, com identificação de condições associadas e melhores tratamentos de suporte, incluindo intervenções clínicas e cirúrgicas. Além disso, com as descobertas no campo da genética, incluindo técnicas de interferência de RNA e de edição genética, novas perspectivas de tratamento começaram a surgir. No presente trabalho, relatamos os marcos mais importantes sobre a pesquisa de CMT no Brasil e fornecemos uma revisão abrangente sobre tópicos como frequência de diferentes genes associados à CMT em nossa população, prevalência de dor, impacto na gravidez, alterações respiratórias e desenvolvimento de novas terapias.

Kidney Retransplantation Outcomes: A Paired Recipient Control Study.

BACKGROUND: Despite progressive improvements in graft and patient survival after kidney transplantation over the last decades, an increasing number of patients are waitlisted for retransplantation. Identifying the risk factors for second graft failure can help us improve management for such patients. The aim of this study was to compare the outcomes of kidney retransplantation with those of first transplantation. METHODS: This retrospective study included all the recipients of a second kidney transplant between January 2008 and December 2019. For each patient with a second kidney transplant, we selected the paired recipient from the same donor. We excluded recipients of donations from living donors, patient-and-donor pairs with more than 1 transplant, and patients without a pair. The follow-up took place December 31, 2020. We included 152 patients, corresponding to 76 pairs of recipients. RESULTS: Patients who underwent a second transplant had significantly higher panel reactive antibody values and longer waiting time for retransplantation. Biopsy-proven acute rejection episodes were doubled in patients undergoing a second transplant (P = .12). There was a lower survival of second grafts at the first, fifth, and 10th year (P < .05). The main factor influencing graft loss for both groups was acute rejection, and, in patients, with a second transplant, acute rejection increased the risk of graft loss by 17 times (odds ratio, 17.5; 95% confidence interval, 4.19-98). CONCLUSIONS: The clinical results of second kidney transplants still fall short of first transplants, with the main factor of poor prognosis being acute rejection. In young patients, allocation and immunosuppression management should consider this risk to improve long-term outcomes.

Kidney Retransplant: Not Too Old for a Second Chance.

BACKGROUND: Kidney retransplant outcomes in the elderly are not well established. Our aim was to compare major clinical outcomes between patients older and younger than 60 years old at retransplant and between first and second kidney transplant (KT) for recipients older than 60 years old. METHODS: We performed a retrospective, longitudinal study that included all patients who underwent KT between January 2008 and December 2019. We defined 3 groups according to recipient age and retransplant status: group 1, patients ≥60 years old and retransplant; group 2, patients <60 years old and retransplant; group 3, patients ≥60 years old and first kidney transplant. We compared clinical outcomes such as acute rejection, death-censored graft survival, and patient survival between groups. RESULTS: We included 109 patients with a second KT, including 13 older than 60 years old (group 1) and 96 younger than 60 years old (group 2). There were no differences in death-censored graft survival or patient survival. There were no biopsy-proven acute rejections for older patients compared with 21 events in the younger group. Regarding differences between retransplant (group 1, n = 13) and first kidney transplant (group 3, n = 390) in patients older than 60 years old, there were no differences in death-censored graft survival at 1 and 5 years or in patient survival. CONCLUSIONS: In our study, major clinical outcomes of retransplant in the elderly were similar to those of their younger counterparts with a second graft and with those of older patients with a first graft.

Clinical Predictors and Prognosis of Recurrent IgA Nephropathy in the Kidney Allograft.

Introduction: Although IgA nephropathy (IgAN) is the most common recurrent glomerulonephritis encountered in the kidney allograft, the clinical and immunogenetic characteristics remain poorly understood. We sought to study determinants and prognosis of recurrent IgAN with special focus on HLA antigens. Materials and Methods: Between 2005 and 2019, we identified 282 transplanted patients with failure secondary to IgAN from two North American and one European Medical Centers, including 80 with recurrent IgAN and 202 without recurrence. Prevalence of HLA antigens was compared to external healthy controls of European ancestry (n=15,740). Graft survival was assessed by Kaplan-Meier method and log rank test. Cox proportional hazards were used for multivariable analyses. Results: Compared to external controls of European ancestry, kidney transplant recipients of European ancestry with kidney failure secondary to IgAN had higher frequency of HLA-DQ5 (42% vs. 30%, OR=1.68, P=0.002) and lower frequency of HLA-DR15 (15% vs. 28%, OR=0.46, P<0.001) and HLA-DQ6 (32% vs. 45%, OR=0.59, P=0.003); however, the frequency of these HLA antigens were similar in recurrent versus non-recurring IgAN. Younger recipient age at transplantation was an independent predictor of recurrence. HLA-matching was an independent predictor for recurrent IgAN only in recipients of living-related but not deceased or living unrelated transplants. Recurrent IgAN was an independent predictor of allograft failure, along with acute rejection. In patients with recurrent IgAN, serum creatinine at biopsy, degree of proteinuria, and concurrent acute rejection were associated with inferior allograft survival. Discussion/ Conclusion: Recurrent IgAN negatively affects allograft survival. Younger recipient age at transplantation is an independent predictor of recurrent IgAN, while the presence of HLA antigens associated with IgAN in the native kidney and HLA-matching in recipients of deceased or living unrelated transplants are not.

The type of SARS-CoV-2 vaccine influences serological response in kidney transplant recipients.

Vaccination is a promising strategy to control the ongoing pandemic; however, solid organ recipients tend to develop a weaker immune response to vaccination. Anti-spike SARS-CoV-2 antibodies titers were measured 2-4 weeks post-vaccination completion in 131 KT patients without previous infection. Demographic, clinical, and laboratorial parameters were analyzed to identify which factors contributed to seroconversion. Factors that influenced seroconversion, that occurred in 76 patients (58%), were longer time post-transplant, immunosuppression without an antiproliferative drug and vaccination with mRNA vaccines. Patients who received mRNA vaccines had significantly higher rates of seroconversion compared with adenovirus vector vaccines (67% vs 33%, P < .001) and higher anti-spike IgG titers. These findings reinforce the need to discuss the vaccination strategy in this population, including a third dose with a mRNA vaccine.

Borderline Changes in Renal Transplantation: Are We Aware of the Real Impact in Graft Survival?

BACKGROUND: Borderline changes suspicious for acute T-cell-mediated rejection (BC) are frequently seen on biopsy specimens, but their clinical significance and clinical management are still controversial. Our goal was to compare clinical outcomes of kidney transplant recipients with biopsy-proven BC vs acute T-cell-mediated rejection (aTCMR) and the influence of treating BC on graft outcomes. METHODS: A retrospective cohort study was performed in all kidney transplant recipients with biopsy-proven BC and aTCMR between January 2012 and December 2018, according to Banff 2017 criteria; patients with concomitant antibody-mediated rejection were excluded. RESULTS: We included 85 patients, 30 with BC (35.3%) and 55 with aTCMR (64.7%). There was no difference between groups regarding demographics, HLA matching and sensitization, immunosuppression, or time of transplant. Treatment with steroids was started in 15 patients with BC (50%) and in all patients with aTCMR, with 4 of the latter additionally receiving thymoglobulin (7.2%). At 1 year post biopsy, overall graft survival was 71%, and despite presenting better estimated glomerular filtration rate (eGFR) at biopsy (33.3 ± 23.4 vs 19.9 ± 13.2 mL/min/1.73 m2, P = .008), patients in the BC group presented the same graft survival as the aTCMR group according to Kaplan-Meyer survival curves. When analyzing the BC group (n = 30) and comparing the patients who were treated (n = 15) vs a conservative approach (n = 15), graft survival at 1 year was 87% for treated patients and 73% for nontreated patients (P = .651), with no difference in eGFR for patients with functioning graft. However, at longer follow-up, survival curves showed a trend for better graft survival in treated patients (70.2 ± 9.2 vs 38.4 ± 8.4 months, P = .087). CONCLUSION: Our study showed that patients with BC did not present better graft survival or graft function at 1 year after biopsy or at follow-up compared with the aTCMR group, despite better eGFR at diagnosis. We found a trend for better graft survival in patients with BC treated with steroids compared with a conservative approach. These results reinforce the importance of borderline changes in graft outcomes and that the decision to treat can influence long-term outcomes.

Arteriovenous graft in kidney transplant patients: Lookout for the rare but fearsome angiosarcoma.

INTRODUCTION: Angiosarcomas are rare tumors, comprising less than 1% of all sarcomas. However, they portend a poor prognosis, as they tend to metastasize early, being of uttermost importance a prompt diagnosis and treatment. CASE DESCRIPTION: We present the case of a 55-year-old female with history of kidney transplantation, immunosuppressed with tacrolimus, prednisolone, and mofetil mycophenolate. Fifteen years after the transplant, she developed an ulcerated lesion on the site of a nonfunctioning arteriovenous graft, which was excised. Histology was compatible with a high grade angiosarcoma that invaded the margins, and immunosuppression was switched to everolimus. Staging imaging exams revealed lymph node, muscle, and lung metastases. Shortly after, nodular lesions appeared compatible with local recurrence of the disease, and the patient showed severe deterioration of her clinical condition, being proposed for palliative chemotherapy. However, the disease showed an explosive progression and the patient died before starting the treatment. CONCLUSION: This case emphasizes the importance of including inspection of the vascular access (functioning or not) in regular post-transplant consultation and value any alterations in the attempt of a timely diagnosis. Although rare, angiosarcoma is an important entity that should be considered in the differential diagnosis of soft tissue masses arising from a vascular access, especially in immunocompromised patients. Aggressive treatment should be offered whenever possible.

Acute liver failure due to primary amyloidosis in a nephrotic syndrome: a swiftly progressive course.

AL amyloidosis is a clonal plasma cell proliferative disorder characterised by extracellular tissue deposits of insoluble fibrils derived from κ or λ immunoglobulin light chains. The most common organs affected by AL amyloidosis are the kidney, presenting with nephrotic syndrome and/or progressive renal dysfunction, and the heart, with restrictive cardiomyopathy. Hepatic deposition of fibrils occurs in half the cases but the liver is rarely the predominantly affected organ. The most common presentation of hepatic amyloidosis is hepatomegaly with elevated alkaline phosphatase. Acute liver failure with cholestasis and jaundice is a rare complication, with a prevalence of approximately 5%, and is usually associated with a worse prognosis. We report a case of a 39-year-old man admitted to our nephrology department with an unusual presentation of primary amyloidosis with nephrotic syndrome and acute liver failure, complicated by obstructive cholestasis resulting in death 2 months after diagnosis.

Narrativas infanto-juvenis sobre o trabalho doméstico em Belo Horizonte: histórias de vida das meninas / Narratives children and adolescents about domestic labor in Belo Horizonte

Apresentamos o relatório final da pesquisa "Narrativas infanto-juvenis sobre o trabalho doméstico em Belo Horizonte: histórias de vida das meninas" realizada no período de fevereiro de 2001 a março de 2002, que objetivou compreender de forma mais acurada as condições e os significados produzidos a respeito da experiência do trabalho doméstico entre adolescentes de onze a dezoito anos. Os dados obtidos através das histórias de vida das adolescentes com trajetória de emprego doméstico foram incorporados à primeira fase do "Projeto erradicação do trabalho doméstico e adequação do trabalho adolescente no serviço doméstico - OIT.

This is the final report of the research "Infant-juvenile narratives of domesticwork in Belo Horizonte: the girls' life story", carried out from February2001 to March 2002. The research aimed at a more accurate understandingof the conditions and meanings produced concerning the experience of do-mestic work shared by adolescents from eleven to eighteen years of age. Thedata collected from the life story of adolescents engaged in domestic workwere incorporated in the first stage of the 'Project for the eradication of do-mestic work and the adequacy of adolescent labour to domestic work ­ OIT'

Esclerosis sistémica progresiva / Progressive Systemic Sclerosis

Se presenta el caso de una niña de 8 años con esclerosis sistémica progresiva, se señala si se trata de una forma sistémica infantil, de la cual hay muy pocos casos publicados y a favor de lo cual hay signos de afectación general; o si se trata de una forma localizada tipo morfea ya estabilizada, y que podría explicar la totalidad de la clínica. Se exponen las características de nuestro caso, así como la conducta asociada en su estudio y terapéutica.

The case of an 8 year-old girl with Progressive Systemic Sclerosis is presented, it is pointed out if you if is an infantile systemic form, of wich there are very few published cases and in favour of which there are signs of general affectation, or if it is a localized form, type morhpea, already estabilized, and which could explain the clinical manifestations. The charactistics of our case are exposed , as well as the measures associated with is study and treatment .

Drenaje biliar: su utilización en el diagnóstico de la giardiasis / Biliary drainage: its use in the diagnosis of giardiasis

Se estudian 19 pacientes pediátricos durante el año 1985, a los cuales se les realizó drenaje biliar previa negativización de heces fecales en busca de Giardia lamblia. El 40,1 % de dichos pacientes fue positivo de este parásito. Se informa que el grupo de edades más frecuentemente afectado fue el que corresponde al de 1 a 5 años, con 92 pacientes (46,8 %), y el sexo pedominante, el masculino (57,6%). Se enfatiza en lo positivo y negativo de nuestra casuística