Podocytopathies associated with familial partial lipodystrophy due to LMNA variants: report of two cases.

Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephroticrange proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and tonephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.

Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review.

Large-scale COVID-19 vaccination has been one of the most effective strategies to control the spread of the SARS-CoV-2 virus. However, several cases of glomerular injury related to the COVID-19 vaccine have been described in the literature. We report two cases of a tip lesion variant of focal segmental glomerulosclerosis (FSGS), which presented with significant proteinuria and improved after immunosuppression. In our literature review, the tip lesion variant of FSGS is currently the most frequent variant associated with vaccination against COVID-19. Prognosis is favorable and without significant alterations in the tubulointerstitial or vascular compartments. Adverse effects of vaccines need to be recognized early and will help us to understand the immune and pathological mechanisms of kidney damage.

Primary Effusion Lymphoma: A Rare and Challenging Diagnosis for Recurrent Pleural Effusion.

Primary Effusion Lymphoma is an extremely rare and aggressive subtype of B-cell lymphoma, accounting for only <1% of all cases of this neoplasm. It has a unique clinical presentation because it has a predilection for appearing in body cavities, such as the pleural space, pericardium and peritoneum. It mainly affects immunocompromised individuals and may also affect individuals in the Mediterranean region and in areas endemic for human herpesvirus 8 (HHV-8). Herein, we report the case of an 83-year-old immunocompetent male complaining of coughing, fever and progressive dyspnea for 3 days. His past medical history revealed a recurrent pleural effusion for the last three years, as well as losing weight and malaise. A subsequent investigation revealed a PEL diagnosis of the pleura.

Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib, or nilotinib: A cohort study using data from a large multinational collaborative network.

Background: Breakpoint cluster region-Abelson gene (BCR-ABL) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs. Objectives: This study aims to compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) < 50%, and venous thromboembolic events (VTE) in patients with CML treated with BCR-ABL TKIs, using data from a large multinational network. Methods: Patients aged ≥ 18 years with CML treated with imatinib, dasatinib, or nilotinib without prior cardiovascular or cerebrovascular disease were included. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated. Results: We identified 3,722 patients with CML under treatment with imatinib (n = 1,906), dasatinib (n = 1,269), and nilotinib (n = 547). Patients with imatinib compared to dasatinib showed a higher hazard ratio (HR) for ACE (HR 2,13, 95% CI 1.15-3.94, p = 0.016). Patients with imatinib presented a lower HR than nilotinib for ACE (HR 0.50, 95% CI 0.30-0.83, p = 0.0074). In relation to heart failure or LVEF < 50%, patients with imatinib had a higher HR than dasatinib (HR 9.41, 95% CI 1.22-72.17, p = 0.03), but no significant difference was observed between imatinib and nilotinib (HR 0.48, 95% CI 0.215-1.01, p = 0.064). Conclusion: In this retrospective study with a large number of patients with CML, those treated with nilotinib had a higher 5-year ratio of ACE, while patients with dasatinib showed a lower ratio than patients with imatinib. The ratio of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib.

The relationship between chikungunya virus and the kidneys: A scoping review.

Several atypical forms of chikungunya fever (CHIK) have been described, including neurological, cardiac and renal involvement. These forms may be related to high morbidity and mortality rates. This scoping review based on the PubMed, Scopus, and WOS databases aims to identify and summarise all the available evidence regarding the clinical and histopathological presentations and risk factors associated with kidney injury related to CHIK, as well as the clinical impact. Thus, a total of 54 papers were selected from 1606 initial references after applying the defined inclusion criteria. Data on the association between kidney injury and CHIK are scarce, with studies only conducted in the acute phase of the disease, lacking further characterisation. Kidney injury incidence in hospitalised patients using the Kidney Disease Improving Global Outcomes criteria varies from 21% to 45%, being higher among patients with atypical and severe manifestations. Although acute kidney injury does not seem to be related to viraemia, it may be related to higher mortality. Few studies have described the renal histopathological changes in the acute phase of CHIK, with prevalent findings of acute interstitial nephritis with mononuclear infiltrate, glomerular congestion and nephrosclerosis. Only one study assessed the kidney function of patients in the subacute and chronic phases of CHIK. Additionally, individuals with comorbidities, including chronic kidney disease, may be among those with a greater risk of presenting worse outcomes when affected by CHIK. The results described herein may contribute to better understand the relationship between the kidneys and chikungunya virus.

ANCA-associated glomerulonephritis and lupus nephritis following COVID-19 vaccination: a case report and literature review.

With the coverage of COVID-19 vaccination, it has been possible to observe the potential side effects of SARS-CoV-2 vaccines, with the most common ones being fever, myalgia, headache, and fatigue. However, an association has been observed between new and recurrent kidney injuries, mainly glomerulonephritis and lupus nephritis associated with ANCA, with the Pfizer-BioNTech, Moderna, Sinovac, and AstraZeneca vaccines, although the relationship between them is not clear. We report a case of ANCA-related vasculitis and lupus glomerulonephritis after the second dose of the AstraZeneca vaccine. The elderly patient presented significant worsening of kidney function after immunosuppression and complications after a new onset COVID-19 infection that led to death. We provide a literature review about kidney damage related to ANCA vasculitis after COVID-19 vaccine, aiming for a better understanding of the pathophysiological mechanism of kidney injury, its presentation, and treatment.

Kidney injury associated with COVID-19 infection and vaccine: A narrative review.

The respiratory tract is the main infection site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in many admissions to intensive care centers in several countries. However, in addition to lung involvement, kidney injury caused by the novel coronavirus has proven to be a significant factor related to high morbidity and mortality, alarming experts worldwide. The number of deaths has drastically reduced with the advent of large-scale immunization, highlighting the importance of vaccination as the best way to combat the pandemic. Despite the undeniable efficacy of the vaccine, the renal side effects associated with its use deserve to be highlighted, especially the emergence or reactivation of glomerulopathies mentioned in some case reports. This study aimed to identify the main renal morphological findings correlated with COVID-19 infection and its vaccination, seeking to understand the pathophysiological mechanisms, main clinical features, and outcomes.

Dialysis-related constrictive pericarditis: old enemies may sometimes come back / Pericardite Constritiva relacionada a diálise: velhos inimigos podem, às vezes, voltar

ABSTRACT Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Several heart conditions have been associated with CKD, including myocardial and pericardial diseases. This paper describes a case of Dialysis-related constrictive pericarditis in a patient diagnosed with sudden hypotension during a hemodialysis session. A 65-year-old man diagnosed with hypertension, diabetes, obesity, and cirrhosis on hemodialysis for two years complained of symptoms during one of his sessions described as malaise, lipothymia, and confusion. The patient had a record of poor compliance with the prescribed diet and missed dialysis sessions. He was sluggish during the physical examination, and presented hypophonetic heart sounds, a blood pressure of 50/30mmHg, and a prolonged capillary refill time. The patient was referred to the intensive care unit and was started on antibiotics and vasoactive drugs. His workup did not show signs of infection, while electrocardiography showed low QRS-wave voltage. His echocardiogram showed signs consistent with a thickened pericardium without pericardial effusion. Cardiac catheterization showed equalization of diastolic pressures in all heart chambers indicative of constrictive pericarditis. The patient underwent a pericardiectomy. Examination of surgical specimens indicated he had marked fibrosis and areas of dystrophic calcification without evidence of infection, consistent with Dialysis-related constrictive pericarditis. Hypotension for unknown causes must be considered in the differential diagnosis of dialysis patients.

RESUMO A doença cardiovascular é a principal causa de morte em pacientes com doença renal crônica (DRC). Várias formas de acometimento cardíaco têm sido associadas. à DRC, incluindo doenças miocárdicas e pericárdicas. Este artigo descreve um caso de pericardite constritiva relacionada a em um paciente diagnosticado com hipotensão súbita durante uma sessão de hemodiálise. Um homem de 65 anos com diagnósticos prévios de hipertensão, diabetes, obesidade e cirrose em hemodiálise por dois anos queixou-se de sintomas durante uma de suas sessões, descritos como mal-estar, lipotímia e confusão mental. Apresentava histórico de baixa adesão à dieta prescrita e faltas frequentes às sessões de diálise. Ele estava fraco durante o exame físico e apresentava bulhas cardíacas hipofonéticas, pressão arterial de 50/30mmHg e tempo de enchimento capilar prolongado. O paciente foi encaminhado para a unidade de terapia intensiva e iniciou o tratamento com antibióticos e drogas vasoativas. Investigação laboratorial não mostrou sinais de infecção, enquanto o eletrocardiograma mostrou baixa voltagem de complexo QRS. Seu ecocardiograma evidenciou sinais consistentes com um pericárdio espessado, sem derrame pericárdico. O cateterismo cardíaco mostrou equalização das pressões diastólicas em todas as câmaras cardíacas, indicativo de pericardite constritiva. O paciente foi submetido a uma pericardiectomia. O exame anatomopatológico mostrou sinais de acentuada fibrose acentuada fibrose e áreas de calcificação distrófica sem evidência de infecção, consistente com pericardite constritiva relacionada a por diálise. A hipotensão por causas desconhecidas deve ser considerada no diagnóstico diferencial de pacientes em diálise.

Case report: Isolated tubular basement membrane deposits in a patient with systemic lupus erythematosus - A diagnostic challenge.

Lupus nephritis is one of the most serious and frequent manifestations of systemic lupus erythematosus. It usually presents in the first years of the disease, which suspicion should be raised in cases of elevated serum creatinine, presence of proteinuria above 500 mg/day or active urinary sediment, in the absence of other apparent causes such as urinary tract infection and use of nephrotoxic drugs. In most cases, it affects the glomerulus, and its presentation is rare in the form of isolated tubulo-interstitial disease. In this report, we describe a case of lupus nephritis diagnosed after 2 years of illness, in the form of atypical isolated tubular disease, characterized by massive deposits in the tubular basement membrane. Clinically, there were altered renal function, subnephrotic proteinuria, and evolution to a complete clinical response after immunosuppressive treatment.

Case Report: Azathioprine: An Old and Wronged Immunosuppressant.

Mycophenolate rapidly substituted azathioprine (AZA) in transplant immunosuppression regimens since the 1990s, when early clinical trials indicated better outcomes, although opposite results were also observed. However, none of these trials used the well-established optimization methods for AZA dosing, namely, thiopurine methyltransferase pharmacogenetics combined with monitoring of the thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). Resistance to optimize AZA therapy remains today in transplant therapy, despite the fact that thiopurine metabolite testing is being used by other medical disciplines with evident improvement in clinical results. In a previous analysis, we found that active 6-TGN metabolites were not detectable in about 30% of kidney transplant patients under continuous use of apparently adequate azathioprine dosage, which demonstrates the need to monitor these metabolites for therapeutic optimization. Two of four case studies presented here exemplifies this fact. On the other hand, some patients have toxic 6-TGN levels with a theoretically appropriate dose, as seen in the other two case studies in this presentation, constituting one more important reason to monitor the AZA dose administered by its metabolites. This analysis is not intended to prove the superiority of one immunosuppressant over another, but to draw attention to a fact: there are thousands of patients around the world receiving an inadequate dose of azathioprine and, therefore, with inappropriate immunosuppression. This report is also intended to draw attention, to clinicians using thiopurines, that allopurinol co-therapy with AZA is a useful therapeutic pathway for those patients who do not adequately form active thioguanine metabolites.

Membranous Nephropathy Secondary to Graves' Disease: A Case Report.

Membranous nephropathy (MN) is a form of kidney disease that is idiopathic in 70%-80% of cases. Glomerular involvement in autoimmune thyroiditis can occur in 10%-30% of patients, and MN manifests in association with Hashimoto thyroiditis in up to 20% of the cases with glomerular involvement. Reports of MN associated with Graves' disease (GD) are extremely rare in the current literature. Herein, we report the case of a 46-year-old man admitted to the hospital with nephrotic syndrome and symptomatic hyperthyroidism due to GD. Kidney biopsy revealed a secondary MN pattern. Immunohistochemical staining for PLA2R was negative, and thyroglobulin showed weak and segmental staining along the glomerular capillary. Anti-thyroid peroxidase (TPO) antibody test was not performed. The patient was treated for GD with methimazole and prednisone, and despite reaching clinical improvement after 8 months, proteinuria remained close to nephrotic levels. In this scenario, the patient was submitted to radioactive iodine, and there was a dramatic reduction in proteinuria levels after treatment. In conclusion, GD association with MN is rare, and when present, diagnosis using PLA2R and immunohistochemistry can be useful in determining association. In addition, radioactive iodine therapy can be an effective treatment modality when preceded with immunosuppressive corticosteroid therapy.

The role of vacuum-assisted mechanical thrombectomy in the management of acutely thrombosed arteriovenous fistulas and grafts.

PURPOSE: The purpose of this study is to evaluate the safety and efficacy of the mechanical thrombectomy with the Indigo System in the treatment of thrombosed arteriovenous fistulas and grafts. METHODS: A retrospective search of endovascular procedures performed from November 2018 to June 2020 was conducted. Inclusion criteria were: acute arteriovenous fistula or graft thrombosis that underwent endovascular mechanical thrombectomy with Indigo System. The following information was collected from each case: sex, age, fistula modality, fistula location, treatment modality, and outcomes. Endpoints evaluated were: technical and clinical success rates; primary, assisted primary, and secondary patency rates; complication rates. RESULTS: Twenty-six mechanical thrombectomy procedures for declotting of arteriovenous fistula thrombosis, using the Indigo System, were performed in 22 patients. Technical and clinical success was achieved in 23/26 cases (88%). Mean follow-up was 9 months (range 11-539 days). The 6-month primary, primary assisted, and secondary patency rates were 71%, 86%, 93% and the 12-month primary, primary assisted, and secondary patency rates were 71%, 72%, 80%, respectively. No technical or device-related complications were observed during thrombectomy, however two venous ruptures occurred on the angioplasty of the underlying stenosis. CONCLUSION: In conclusion, vacuum-assisted thrombectomy of acutely thrombosed arteriovenous fistulas and grafts with Indigo System is safe and effective, providing good short term patency rates.

Dialysis-related constrictive pericarditis: old enemies may sometimes come back.

Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Several heart conditions have been associated with CKD, including myocardial and pericardial diseases. This paper describes a case of Dialysis-related constrictive pericarditis in a patient diagnosed with sudden hypotension during a hemodialysis session. A 65-year-old man diagnosed with hypertension, diabetes, obesity, and cirrhosis on hemodialysis for two years complained of symptoms during one of his sessions described as malaise, lipothymia, and confusion. The patient had a record of poor compliance with the prescribed diet and missed dialysis sessions. He was sluggish during the physical examination, and presented hypophonetic heart sounds, a blood pressure of 50/30mmHg, and a prolonged capillary refill time. The patient was referred to the intensive care unit and was started on antibiotics and vasoactive drugs. His workup did not show signs of infection, while electrocardiography showed low QRS-wave voltage. His echocardiogram showed signs consistent with a thickened pericardium without pericardial effusion. Cardiac catheterization showed equalization of diastolic pressures in all heart chambers indicative of constrictive pericarditis. The patient underwent a pericardiectomy. Examination of surgical specimens indicated he had marked fibrosis and areas of dystrophic calcification without evidence of infection, consistent with Dialysis-related constrictive pericarditis. Hypotension for unknown causes must be considered in the differential diagnosis of dialysis patients.

Evaluation of central venous catheter and other risk factors for mortality in chronic hemodialysis patients with COVID-19 in Brazil.

PURPOSE: Hemodialysis patients with COVID-19 are at increased risk of death. We aimed to describe the characteristics of a cohort of Brazilian hemodialysis patients with COVID-19 and assess their mortality rate and risk factors for death. METHODS: Retrospective cohort study of 741 Brazilian hemodialysis patients with confirmed COVID-19 from Feb-Dec/2020, of 52 dialysis centers of the country. We analyzed comorbid conditions, sociodemographic factors, and dialysis-related parameters. To detect risk factors for mortality in hemodialysis patients, we performed multivariable Cox proportional hazard regression analysis. Survival was analyzed by Kaplan-Meier. RESULTS: From 9877 hemodialysis patients, 741 were diagnosed with COVID-19. Mean age was 57 ± 16 years, 61% were male, and 51% white. The most frequent symptoms were fever (54.1%), cough (50.9%), and dyspnea (37.2%); 14.2% were asymptomatic. There were 139 deaths (18.8%), with 66% within the disease's first 15 days. 333 patients (44.9%) required hospitalization, and 211 (28.5%) were admitted to an intensive care unit. The cumulative probability of survival at 90 days of diagnosis was 79% (95% CI 76-82%). In the fully adjusted multivariate model, the risk factors significantly associated with death were diabetes mellitus (HR 1.52, 95% CI 1.05-2.19, P = 0.026), use of a central venous catheter (CVC) (HR 1.79, 95% CI 1.22-2.64, P = 0.003), age (HR 1.03, 95% CI 1.01-1.04, P < 0.001), and origin from the North vs. Southeast region (HR 2.60, 95% CI 1.01-6.68, P = 0.047). CONCLUSIONS: Hemodialysis patients using a CVC as the vascular access, aside from diabetic and elderly ones, should be closely monitored due to their high risk of death in the course of the COVID-19.

Thrombotic microangiopathy associated with arboviral infection: Report of 3 cases.

Dengue fever and chikungunya are viral diseases that have spread rapidly throughout the world in recent decades. The occurrence of complications is well known, including prerenal acute kidney injury (AKI), which is usually thought to be caused by dehydration and fluid loss. Thrombotic microangiopathy (TMA) is an uncommon aggravation of dengue fever and chikungunya, with only a few cases described in the medical literature. The aim of this study is to present 3 cases of TMA associated with arboviral infection. Three patients with clinical history, laboratory test, and kidney biopsy results compatible with TMA were selected for the study, 2 of whom had a serological diagnosis of dengue fever and 1 of chikungunya. The 3 patients were followed up at the Federal University of Maranhão Hospital's Nephrology Service in 2018. A targeted gene panel sequencing (TGPS) plus multiple to atypical hemolytic uremic syndrome (aHUS) multiplex ligation-dependent probe amplification (MLPA) was performed in 2 of the patients and revealed in the patient 1 a heterozygous pathogenic variant in the gene THBD, as well as heterozygous deletions in CFH, CFHR1, and CFHR3. In the patient 2, there were heterozygous pathogenic variant in the genes CFI and CFB, in addition to heterozygous deletions in the genes CFHR1 and CFHR3. Both received treatment with eculizumab and undergone recovery of renal function. The third patient had TMA not classified as either aHUS or thrombotic thrombocytopenic purpura (TTP); he abandoned the treatment and returned to the service after 2 years for a dialysis emergency. Patients with arboviral infectious disease and changes that suggest TMA should have appropriate support to establish early diagnosis and useful treatment.

Methimazole-Induced ANCA Vasculitis: A Case Report.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves' disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m2), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm3, platelets 238,000/mm3, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m2) and negative p-ANCA.

Multisystemic Inflammatory Syndrome and Thrombotic Microangiopathy as Complications of COVID-19 in a Child: A Case Report.

Clinical presentations of the novel coronavirus (SARS-CoV-2) infection are quite varied, ranging from asymptomatic conditions to potentially fatal disease. The kidney is one of the affected targets of coronavirus disease (COVID-19) complications, and renal dysfunction is a significant prognostic factor for mortality. This report describes a series of clinical complications in a previously healthy child who developed nephritic syndrome with a concomitant SARS-CoV-2 infection. These complications include acute kidney injury that progressed to chronicity, multisystemic inflammatory syndrome, Kawasaki-like syndrome, and thrombotic microangiopathy.

Acute Kidney Injury Due to COVID-19 in Intensive Care Unit: An Analysis From a Latin-American Center.

Introduction: The kidney may be affected by coronavirus (COVID-19) in the setting of acute kidney injury (AKI). Data about AKI in intensive care unit (ICU) patients in Latin America are scarce. We aimed to evaluate the risk of AKI, dialysis (HD), and death in ICU COVID-19 patients in a Brazilian center. Methods: Analysis from medical records of COVID-19 patients in a Brazilian center. Results: A total of 95 patients were analyzed. There was male predominance (64.2%), median age: 64.9 years, and previous history of hypertension and diabetes in 51.6 and 27.4%, respectively. AKI was diagnosed in 54 (56.8%) patients, and 32 (59.2%) of them required HD. Mortality rate was 17.9%. AKI patients when compared with no-AKI were more frequently hypertensive/diabetic and more often needed organ support therapies. Workups depicted more anemia, lymphopenia, and higher levels of inflammatory markers and higher mortality. Comparing patients who had undergone death to survivors, they were older, more frequently diabetic, and had worse SAPS3 and SOFA scores and need for organ support therapies, AKI, and HD. Multinomial logistic regression revealed that hypertension (p = 0.018) and mechanical ventilation (p = 0.002) were associated with AKI; hypertension (p = 0.002), mechanical ventilation (p = 0.008), and use of vasopressor (p = 0.027) to HD patients; and age >65 years (p = 0.03) and AKI (p = 0.04) were risk factors for death. Conclusions: AKI was a common complication of ICU COVID-19 patients, and it was more frequent in patients with hypertension and need of organ support therapies. As well as age >65 years, AKI was an independent risk factor for death.

The effect of sirolimus on angiomyolipoma is determined by decrease of fat-poor compartments and includes striking reduction of vascular structures.

Renal angiomyolipomas hemorrhage is associated with their size and vascular constitution. The effects of sirolimus on different components of angiomyolipomas was analyzed in patients with tuberous sclerosis complex, sporadic lymphangioleiomyomatosis and multiple sporadic angiomyolipomas. Thirty angiomyolipomas from 14 patients treated with sirolimus were retrospectively evaluated. A Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. A median reduction of 100% (75 to 100) in the diameter of aneurysmatic/ectatic vascular structures was observed. Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels, revealing the likely mechanism responsible for the risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. These findings support the role of mTOR in the development of angiomyolipoma blood vessels.