Aortoarteritis: A rare pulmonary-renal disease

Takayasu arteritis (TAK) is an autoimmune disease majorly affecting young females. It alters the vascular wall, resulting in stenosis, occlusion, or dilatation. It has no distinct clinical manifestation. Here, we present the case of an 18-year-old girl who presented with generalized tonic-clonic seizure and hypoxia. Blood investigations showed deranged urea and creatinine values. Computed tomography angiography revealed bilateral artery occlusion, decreased kidney size, and pulmonary artery dilatation, confirming generalized vascular disease that caused hypertension and ischemic nephropathy in the patient. Our case represents a rare autoimmune disease, leading to pulmonary hypertension and renal artery stenosis. TAK should be considered as a differential diagnosis in young female patients presenting with pulmonary as well as renal signs and symptoms, especially if there is discrepancy in blood pressure levels in all limbs.

Estudo da morfologia e status oxidativo em rim de ratos com nefropatia isquêmica após tratamento com células-tronco mesenquimais de tecido adiposo / Study of morphology and oxidative status in kidney of rats with ischemic nephropathy after treatment with adipose tissue mesenchymal stem cells

A nefropatia isquêmica é uma doença renal crônica provocada pela redução do fluxo sanguíneo renal que pode progredir para a doença renal terminal, cujo tratamentos disponíveis se baseiam em terapias substitutivas da função renal, como diálise ou transplante renal. No entanto, devido ao alto custo dos tratamentos e a carência de órgãos, se faz necessária a busca por novas terapias, como as células-tronco (CT). Apesar do potencial terapêutico das CT em doenças crônicas, não está claro se essas células mantêm seus efeitos benéficos em órgãos lesionados por tempo prolongado. O objetivo desse estudo foi avaliar os efeitos precoces e tardios do tratamento com células-tronco adiposas (CTA) sobre a morfologia e o status oxidativo em rins de ratos com nefropatia isquêmica. A isquemia renal foi induzida pelo modelo 2rins-1clip (2R1C) e, depois de um mês da clipagem da artéria renal, foram injetadas 106 células-tronco na região subscapsular do rim afetado. Após 15 e 30 dias da injeção das CTA, a morfologia renal foi verificada por meio da análise macroscópica, microscópica e ultraestrutural. Além disso, o status oxidativo foi avaliado no tecido renal através da mensuração da atividade das enzimas antioxidantes catalase e glutationa peroxidase; e de marcadores biológicos de dano oxidativo, como proteínas carboniladas, 3-Nitrotirosina e 4-Hidroxinonenal. Por imunoperoxidase foi possível localizar as células-tronco adiposas GFP+ foram rastreadas e encontradas tanto 15 dias, quanto 30 dias após a injeção na região subcapsular. A restauração da arquitetura renal foi evidenciada 15d após o uso das células, onde detectamos redução na deposição de fibras colágenas no parênquima renal, o que não foi observado 30d após o uso das células. Os resultados também foram confirmados através da análise da ultraestrutura renal que mostraram restauração da arquitetura renal no grupo de 15d, não evidenciada no grupo de 30d. Quanto a análise do status oxidativo, somente os animais com nefropatia isquêmica mais prolongada apresentaram estresse oxidativo com redução da atividade da enzima antioxidante catalase no tecido renal. Além disso, foi observado dano proteico e lipídico, sem melhora dessa condição nos animais 30d após o tratamento com as células-tronco. No modelo de nefropatia isquêmica avaliado, o tratamento com CTA mostrou benefícios na morfologia renal a curto prazo, mas não tardiamente, apesar da permanência dessas células no tecido. Acreditamos que o estresse oxidativo, evidenciado somente no tecido renal com isquemia mais prolongada, possa ter dificultado a ação das células-tronco, contribuindo para tais achados. Esses resultados abrem perspectivas para o aprofundamento do estudo quanto à caracterização dos mecanimos de ação das CTA nas respostas anti-fibrogênicas, assim como o estabelecimento do número, frequência, vias de administração e melhor momento para uso dessas células no tratamento de doenças renais crônicas.

Ischemic nephropathy is a chronic kidney disease caused by reduced kidney blood flow that can progress to end stage kidney disease, whose available treatments are based on kidney function replacement therapies, such as dialysis or kidney transplantation. However, due to the high cost of treatments and the lack of organs, it is necessary to search for new therapies, such as stem cells (SC). Despite the therapeutic potential of SC in chronic diseases, it is unclear whether these cells maintain their beneficial effects on injured organs for a long time. The aim of this study was to evaluate the early and late effects of adipose-derived stem cells (ADSC) treatment on the morphology and oxidative status in kidneys of rats with ischemic nephropathy. Renal ischemia was induced by the 2kidneys-1clip (2K1C) model and, after a month of clipping the renal artery, 106 stem cells were injected into the subscapsular region of the affected kidney. After 15 and 30 days of ADSC injection, renal morphology was verified by macroscopic, microscopic, and ultrastructural analysis. In addition, oxidative status was assessed in renal tissue by measuring the activity of the antioxidant enzymes catalase and glutathione peroxidase; and biological markers of oxidative damage, such as carbonylated proteins, 3-nitrotyrosine and 4-hydroxynonenal. By immunoperoxidase, it was possible to locate GFP + adipose-derived stem cells that were tracked and found both 15 days and 30 days after injection in the subcapsular region. The restoration of the renal architecture was evidenced 15d after the use of the cells, where we detected a reduction in the deposition of collagen fibers in the renal parenchyma, which was not observed 30d after the use of the cells. The results were also confirmed by analyzing the renal ultrastructure, which showed restoration of the renal architecture in the 15d group, not evidenced in the 30d group. Regarding the analysis of oxidative status, only animals with more prolonged ischemic nephropathy presented oxidative stress with reduced activity of the antioxidant enzyme catalase in renal tissue. In addition, protein and lipid damage was observed, with no improvement in this condition in the animals 30d after treatment with stem cells. In the evaluated ischemic nephropathy model, treatment with ADSC showed benefits in renal morphology in the short term, but not late, despite the permanence of these cells in the tissue. We believe that oxidative stress, evidenced only in renal tissue with more prolonged ischemia, may have hindered the action of stem cells, contributing to such findings. These results open perspectives for further study on the characterization of ADSC mechanisms of action in anti-fibrogenic responses, as well as the establishment of the number, frequency, routes of administration and the best time to use these cells in the treatment of chronic kidney diseases.

Nefropatia isquêmica / Ischemic nephropathy

A doença renal isquêmica ou nefropatia isquêmica relacionada à doença renovascular pode evoluir de forma rápida e progressiva para a insuficiência renal crônica. É fundamental a identificação e o tratamento precoces desta condição clínica, prevenindo a ocorrência de doença renal em estágio terminal, com consequente necessidade de terapia de substituição renal. Há uma década, o controle da hipertensão renovascular era o objetivo primário no manejo de pacientes com doença renovascular. Atualmente, a meta está dirigida principalmente para a estabilização e a melhora da função renal, além do controle dos níveis pressóricos.

Ischemic renal disease or ischemic nephropathy related to renovascular disease can progress rapidly and gradually to chronic renal failure. Early diagnosis and treatment is crucial for this clinical condition, because they can prevent occurrence of end-stage renal disease, with consequent need for renal replacement therapy. A decade ago, renovascular hypertension control was the primary objective in the management of patients with renovascular disease. Currently, the goal is addressed primarily to the stabilization and improvement of renal function, in addition to blood pressure control.

Estenosis de la arteria renal: implicaciones clínicas y tratamiento / Renal artery stenosis: clinical implications and treatment

La estenosis de la arteria renal puede ocurrir sola (hallazgo anatómico aislado), o en asociación con hipertensión, insuficiencia renal (nefropatía isquémica) o ambas. Entre las enfermedades primarias vasculares que producen estenosis tenemos: estenosis ateroesclerótica, más frecuente en la sexta década de la vida; y la displasia fibromuscular, que se presenta en mujeres jóvenes. Entre los factores de riesgo tenemos: hipercolesterolemia, diabetes, tabaquismo, factores genéticos. Para el diagnóstico se utilizan procedimientos no invasivos (prueba de captopril, ultrasonografia duplex, tomografía computada, resonancia magnética con gadolinio), e invasivos (angiografía contrastada). El tratamiento está basado en el uso de inhibidores ECA y bloqueantes AT1. Se utiliza con buen resultado la revascularización quirúrgica o revascularización percutánea con balón con o sin stent. En un buen porcentaje de casos se obtiene recuperación de la función renal y mejoría de la hipertensión. El objetivo de esta revisión es tener presente a la estenosis de la arteria renal como una causa de hipertensión arterial potencialmente reversible cuando es detectada a tiempo.

Renal artery stenosis can occur on its own (isolate anatomy discovery), or in association with hypertension, renal failure (ischemic nephropathy) or both. Among the primary vascular illnesses which produce stenosis we have: atherosclerotic stenosis, more frequent in the sixth decade of life; and fibromuscular dysplasia which appears in young women. Among the risk factors we have: hypercholesterolemia, diabetes, tobaccoism and genetic factors. Non- invasive procedures are used for its diagnosis (captopril test, duplex ultrasonography, computerized tomography, magnetic resonance with gadolinium) and invasive (contrastive angiography). The treatment is based on the use of the ACE inhibitors and AT1 blockers. Surgical revascularization or percutaneous revascularization with balloon with or without stent is used with good results. A high percentage of the cases recover their renal function and improve their hypertension condition. The objective of this revision is to keep the renal artery stenosis in mind as a cause of arterial hypertension potentially reversible when detected in time.

Successful Resolution of Left Renal Artery Stenosis by Interventional Renal Angioplasty with Stent in a Patient with Renal Insufficiency Underlying Ischemic Nephropathy / 대한신장학회잡지

Ischemic nephropathy is defined as renal dysfunction due to renal hypoperfusion mainly through renal artery stenosis. It is a common cause of chronic renal failure in old patients with atherosclerosis and is also a potentially correctable cause of renal failure if diagnosed earlier. We experienced a case of sudden Rt. main renal artery occlusion and renal failure after femoral artery angioplasty in an aged male patient with underlying atherosclerotic bilateral renovascular stenosis associated with ischemic nephropathy. He received successful Lt. renal artery angioplasty with stenting and restored Lt. renal artery blood flow. His blood pressure was more easily controlled with fewer antihypertensive drugs after renal artery revascularization. His renal function was recovered to his baseline level and became stabilized thereafter. Early diagnosis of ischemic nephropathy with MRA and timely renal angioplasty with stenting are beneficial to avoiding progression to irreversible renal failure.

Renal Fibrosis Induced by the Partial Reduction of the Diameter of Renal Artery in Mouse / 대한해부학회지

Kidney artery stenosis such as atherosclerosis induces ischemic nephropathy which is caused by the reduction of blood supply to the kidneys. Since useful experimental animal models for the kidney artery stenosis is very limited, the pathophysiology of the ischemic nephropathy induced by the renal artery stenosis remain to be defined. In the present studies, I developed the mouse experimental model of kidney artery stenosis by the reduction of renal artery diameter to the out side diameter of 31-guage needle.The reduction of renal artery diameter reduces kidney size and mass. There is the severe shrink of glomeruli, tubular atrophy and infiltration of l eukocytes. In the kidney subjected to the experiment of the reduction of renal artery diameter. The expression of alpha-smooth muscle actin in the kidney partially tied the renal artery is much greater than that in the contralateral kidney. These results demonstrate that the reduction of renal artery diameter induced renal fibrosis, the reduction of renal blood flow and kidney size and that the experimental models may be useful to study the pathophysiology of ischemic nephropathy induced by renal artery stenosis as well as chronic renal failure which is involved in renal fibrotic responses.