Fetal Tuberous Sclerosis: Sirolimus for the Treatment of Fetal rhabdomyoma.

BACKGROUND: Sirolimus constitutes a safe and effective treatment for cardiac manifestations of tuberous sclerosis complex (TSC) in children but only four cases describing prenatal treatment of rhabdomyomas with mTOR inhibitors have been published. CASE: In this case, sirolimus was initiated at 26 weeks´ gestation in a pregnant woman with TSC with a fetus with a large rabdomyoma conditioning severe arrythmia. There was a significant reduction in the tumor size with ongoing treatment and a partial reversion of the arrythmia. CONCLUSION: m-TOR inhibitors can be considered for severe cases of fetal rhabdomyomas with poor prognosis given its potencial benefits.

Membranoproliferative glomerulonephritis and interstitial nephritis in the setting of Epstein-Barr virus-related hemophagocytic syndrome
.

BACKGROUND: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. Renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. Less frequently, glomerulopathy can also be found. CASE: We report a case of a 24-year-old Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and normal renal function who presented to us with fever. Laboratory findings revealed pancytopenia, elevated lactate dehydrogenase, and ferritin as well as liver and kidney failure. Renal biopsy showed a tubulointerstitial nephritis superimposed in a membranoproliferative glomerulonephritis with crescents. Extensive etiologic investigation was negative except for Epstein-Barr virus (EBV) viral load. EBV-DNA was then identified by in situ hybridization in the renal biopsy. HPS could be diagnosed with the presence of six criteria: fever, splenomegaly, bicytopenia, high ferritin, hypertriglyceridemia, and high levels of soluble CD25. Steroid therapy was initiated with resolution of HPS as well as complete recovery of renal and liver function. CONCLUSION: In this case, we believe that EBV triggered both HPS and tubulointerstitial nephritis. Steroid therapy successfully treated the inflammatory syndrome, allowing renal function recovery without compromising EBV infection resolution.
.

Multiple brown tumors - a rare presentation in the modern era
.

Chronic kidney disease (CKD) commonly evolves with disturbances in mineral and bone metabolism, currently defined as CKD-MBD. Management strategies have progressed over the years, but our knowledge regarding evaluation and treatment is still sparse. Herein, we describe a rare case of a hemodialysis patient with apparently fairly controlled hyperparathyroidism (HPTH), who developed multiple symptomatic brown tumors involving the scull, mandible, vertebrae, pelvis, and metacarpus. Parathyroidectomy allowed complete resolution of the bone lesions preventing disastrous consequences.
.

Secukinumab-induced systemic lupus erythematosus in psoriatic arthritis.

CASE REPORT: A 68-year-old male treated with secukinumab for psoriatic arthritis suspended treatment for three months due to COVID pandemic. Upon secukinumab reintroduction, anorexia and weight loss ensued and four months later he had an abrupt onset of low-grade fever, fatigue, flu-like symptoms, dyspnoea and widespread inflammatory arthralgias. Laboratory investigations showed de novo anaemia, leukopenia, lymphopenia, cytocholestasis, elevated acute phase reactants, C3 complement consumption, proteinuria (1630mg/24h), active urine sediment, positive antinuclear (1:1280) and anti-double-stranded DNA (212.3 IU/mL) antibodies. Chest imaging showed peripheral pulmonary embolism, lobar pneumonia, and a small bilateral pleural effusion. Drug-induced lupus erythematosus (DILE) was suspected, and the patient was hospitalised. Secukinumab was discontinued and treatment with enoxaparin, antibiotics, enalapril, hydroxychloroquine and prednisolone 0.5mg/kg qd was started. Clinical and laboratorial remission ensued after one month except for proteinuria (decreased to 653mg/24h). Proliferative lupus nephritis was assumed and mycophenolate mofetil was introduced, with sustained complete remission over a 33-month follow-up. DISCUSSION: This is the second reported case of systemic secukinumab-associated DILE, and the first with renal involvement. Clinical and laboratory features of DILE are reviewed and compared with previously described cases.

A glance into the future of anti-neutrophil cytoplasmic antibody-associated vasculitis.

In the past decade, unprecedented progress has been made in understanding the pathogenesis, diagnosis, assessment, and treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). International collaborations and input from several fields (e.g. immunology, rheumatology, and nephrology) have been critical for analyzing demographics, disease manifestations, and outcomes in clinical research studies. Such efforts opened new avenues for generating novel questions and rationale to design better clinical trials. In addition, clinical research has been a source of several biological discoveries and the starting point for knowledge seeking on the pathophysiology of AAV. Interestingly, the blending of clinical and basic research provides a platform for personalized medicine. Despite recent revisions on AAV classification, the incorporation of new findings on disease genetics and immunologic responses may soon result in changes in clinical practice. These advances will enhance the selection of more specific and targeted therapies. However, current unmet needs in the management of AAV are still sizable and heavily impact long-term survival. Especially, frequent relapses, damage accrual, and high morbidity contribute to poor outcomes. Finally, the lack of defined biomarkers for disease activity and the prognosis is a permanent challenge in AAV research. Our work provides an overview of the current state of the art in AAV literature and suggests bridges for the remaining knowledge gaps. It offers potential future directions for the clinical assessment, management, and research in the field toward a more personalized medicine approach.

Pregnancy in a woman undergoing peritoneal dialysis: Management and dialysis options.

Pregnancy in patients with end-stage renal disease on maintenance dialysis is uncommon, with annual incidences reported at 0.3 - 2.7%. Peritoneal dialysis usage in pregnancy has been less reported than hemodialysis, although outcomes are similar. Nowadays, there are insufficient data to establish a generalizable dialysis strategy in pregnant women with end-stage renal disease. As such, decisions should be individualized, depending on clinical factors, residual renal function, and, whenever possible, choice of the patient. We report the case of a 22-year-old patient receiving peritoneal dialysis who delivered a full-term, normal weight, healthy baby with increased dialysis dose achieved by supplementary hemodialysis during pregnancy, thus enabling peritoneal dialysis to be continued until the third trimester and minimizing hemodialysis requirements.

Atypical Hemolytic Uremic Syndrome and Nephrotic Syndrome Associated with Cytomegalovirus Infection.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease. It results from the dysregulation of the alternative complement pathway on the cell surface which causes endothelial damage. Increasing evidence links, these abnormalities to mutations in genes of complement regulators or with autoantibodies against complement factors. These mutations have an incomplete penetrance and variable phenotype. Cytomegalovirus (CMV) is endemic throughout the world, and the incidence of severe CMV disease in immunocompetent adults appears to be greater than previously thought. aHUS and nephrotic syndromes associated with CMV infection are rare. Identification of triggers for aHUS manifestation in a genetically susceptible patient is extremely important since this permits a faster initiation of treatment and clinical improvement. We report a case of a man with a homozygotic deletion of CFHR3-1 whose initial presentation was aHUS and nephrotic syndromes associated with CMV infection.

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up.

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign. Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes. Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3-4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2. Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10-05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10-16). Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.

Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis.

BACKGROUND: The Th17 subset has been implicated in the pathogenesis of a number of autoimmune diseases. However, little is known about its role in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). We measured serum levels of IL-17A and associated upstream cytokines and the frequency of IL-17-producing autoantigen-specific T cells in patients with AAV. METHODS: ELISA on sera from acute (n = 28) and convalescent (n = 65) patients with AAV from Hammersmith Hospital was performed for IL-17A and the associated upstream cytokines IL-23, IL-6 and IL-1beta, as well as the Th1 cytokine IFN-gamma. ELISPOT was performed to measure autoantigen-specific recall T cell responses in convalescent patients and the frequency of IL-17- and IFN-gamma-producing cells. RESULTS: Serum IL-17A and IL-23 levels were significantly elevated in acute AAV patients compared to healthy controls (P < 0.01 and P < 0.001, respectively), but importantly, remained elevated in a proportion of convalescent patients. By contrast, no significant differences in IFN-gamma levels were detected between patient groups and controls. Patients with elevated levels of IL-23 compared to those with low IL-23 had more active disease as measured by Birmingham Vasculitis Activity Score (P < 0.05) and had higher ANCA titres (P < 0.05). Critically, immunosuppressive therapy did not always effectively suppress IL-23 or IL-17 production. Additionally, autoantigen-specific IL-17-producing, but not IFN-gamma-producing, cells were significantly elevated in patients during disease convalescence compared to healthy controls. CONCLUSIONS: These data implicate the Th17 axis and specifically IL-23 as mediators of more severe disease in AAV. Their persistence despite conventional treatment may contribute to high relapse rates.

Life-saving vascular access in vascular capital exhaustion: single center experience in intra-atrial catheters for hemodialysis.

INTRODUCTION: Intra-atrial catheter (IAC) placement through an open surgical approach has emerged as a life-saving technique in hemodialysis (HD) patients with vascular access exhaustion. OBJECTIVE: To assess the complications of IAC placement, as well as patient and vascular access survival after this procedure. METHODS: The authors retrospectively analyzed all seven patients with vascular capital exhaustion, without immediate alternative renal replacement therapy (RRT), who underwent IAC placement between January 2004 and December 2015 at a single center. RESULTS: Seven patients were submitted to twelve IAC placements. Bleeding (6/7) and infections (3/7) were the main complications in the early postoperative period. Two (2/7, 29%) patients died from early complications and 5/7 were discharged with a properly functioning IAC. The most frequent late complication was catheter accidental dislodgement in all remaining five patients, followed by catheter thrombosis and catheter-related infections in the same proportion (2/5). During follow-up, two of five patients died from vascular accesses complications. After IAC failure, one patient was transferred to peritoneal dialysis and a kidney transplant was performed in the other. Only one patient remains on HD after the third IAC, with a survival of 50 months. The mean patient survival after IAC placement was 19 ± 25 (0-60) months and the mean IAC patency was 8 ± 11 (0-34) months. CONCLUSION: Placing an IAC to perform HD is associated to significant risks and high mortality. However, when alternative RRT are exhausted, or as a bridge to others modalities, this option should be considered.

Life-saving vascular access in vascular capital exhaustion: single center experience in intra-atrial catheters for hemodialysis / Acesso vascular life-saving na exaustão do capital vascular: experiência de um centro com cateteres intra-auriculares para hemodiálise

Abstract Introduction: Intra-atrial catheter (IAC) placement through an open surgical approach has emerged as a life-saving technique in hemodialysis (HD) patients with vascular access exhaustion. Objective: To assess the complications of IAC placement, as well as patient and vascular access survival after this procedure. Methods: The authors retrospectively analyzed all seven patients with vascular capital exhaustion, without immediate alternative renal replacement therapy (RRT), who underwent IAC placement between January 2004 and December 2015 at a single center. Results: Seven patients were submitted to twelve IAC placements. Bleeding (6/7) and infections (3/7) were the main complications in the early postoperative period. Two (2/7, 29%) patients died from early complications and 5/7 were discharged with a properly functioning IAC. The most frequent late complication was catheter accidental dislodgement in all remaining five patients, followed by catheter thrombosis and catheter-related infections in the same proportion (2/5). During follow-up, two of five patients died from vascular accesses complications. After IAC failure, one patient was transferred to peritoneal dialysis and a kidney transplant was performed in the other. Only one patient remains on HD after the third IAC, with a survival of 50 months. The mean patient survival after IAC placement was 19 ± 25 (0-60) months and the mean IAC patency was 8 ± 11 (0-34) months. Conclusion: Placing an IAC to perform HD is associated to significant risks and high mortality. However, when alternative RRT are exhausted, or as a bridge to others modalities, this option should be considered.

Resumo Introdução: A colocação de cateteres intra-auriculares (IAC) tem surgido como uma técnica life-saving nos doentes em hemodiálise (HD) com exaustão de acessos vasculares. Objetivo: Analisar as complicações decorrentes da colocação de IAC, assim como a sobrevivência dos doentes e do acessos vascular após este procedimento. Métodos: Os autores analisaram retrospetivamente sete doentes com exaustão de acessos vasculares para HD, sem alternativa imediata de terapêutica substitutiva renal, submetidos a colocação de IAC entre Janeiro de 2004 e Dezembro de 2015. Resultados: Os sete doentes foram submetidos à colocação de doze IAC. A hemorragia (6/7) e as infeções (3/7) foram as principais complicações no pós-operatório imediato. Dois (2/7, 29%) doentes faleceram por complicações precoces e 5/7 tiveram alta com cateter funcionante. A complicação tardia mais frequente foi a exteriorização acidental do cateter em todos os doentes, seguida da trombose e infeção relacionada com o cateter, na mesma proporção (2/5). Durante o seguimento, dois dos cinco doentes faleceram por complicações associadas com o acesso vascular. Após a falência do IAC, um doente foi transferido para diálise peritoneal e outro foi submetido a transplantação renal. Apenas um doente permanece em HD após o terceiro IAC, com uma sobrevivência de 50 meses. A sobrevivência média dos doentes após colocação de IAC foi de 19 ± 25 (0-60) meses e a patência média do IAC foi de 8 ± 11 (0-34) meses. Conclusão: A colocação de um IAC para HD esteve associado a riscos significativos e mortalidade elevada. Contudo, quando as terapêuticas de substituição renal alternativas estão esgotadas, ou como uma ponte para outras modalidades, esta opção deve ser considerada.

Teriparatide efficacy in the treatment of severe hypocalcemia after kidney transplantation in parathyroidectomized patients: a series of five case reports.

BACKGROUND: Teriparatide is a recombinant human parathormone (PTH 1-34) currently approved for the treatment of osteoporosis with high risk of fracture. In this study, we analyze the efficacy and safety profile of teriparatide therapy in severe and prolonged hypocalcemia after kidney transplantation in patients previously submitted to parathyroidectomy. METHODS: The authors report results from a series of five hemodialyzed patients (mean age: 50±15 years; three female) previously submitted to parathyroidectomy to control secondary hyperparathyroidism. All patients had developed severe refractory hypocalcemia (calcium minimum levels: 5±1.4 mg/dL) early after kidney transplantation. The effect of teriparatide in calcemia and phosphatemia levels was analyzed, and variations in calcium and vitamin D analog requirements were analyzed. Secondary effects and serum creatinine changes were also ascertained. RESULTS: Teriparatide therapy was initiated 32±14 days after the development of hypocalcemia. As a result, calcemia levels increased (median±standard deviation [SD]: 6.7±0.8 vs. 8.5±0.8 mg/dL, P=0.024) allowing suspension of intravenous calcium in two patients and reduction of calcitriol doses (mean±SD: 1.1±0.38 vs. 0.55±0.27 µg/day, P=0.004). In addition, phosphatemia levels (median±SD: 5.1±1.5 vs. 3.9±0.5 mg/dL, P=0.09) and calcium carbonate requirements (mean±SD: 13.8±9.4 vs. 7.2 ±3.7 g/day, P=0.9) exhibited declining trends. No secondary effects were observed and creatinemia remained stable. CONCLUSIONS: Our data strongly suggest that refractory hypocalcemia after kidney transplantation in patients with low PTH levels can be successfully treated with teriparatide. PTH analog therapy leads to faster normalization of calcemia, permits earlier suspension of intravenous calcium supplementation, and reduces calcitriol requirements.