[Renal pathophysiology and pharmacological mechanisms of nephroprotection]. / Fisiopatología renal y mecanismos farmacológicos de nefroprotección.

Several risk factors may affect the progression of chronic kidney disease (CKD). Arterial hypertension, proteinuria, obesity, intraglomerular hypertension, smoking and metabolic control in diabetes mellitus are the main modifiable risk factors for progression. The progression of CKD involves many cellular processes that originate in specific compartments of the kidney, the vascular compartment with nephroangiosclerosis and the tubulointerstitial compartment with fibrosis and tubulointerstitial atrophy, and there may be overlap between both mechanisms. Given the involvement of so many risk factors and so many pathogenic pathways in the progression of CKD, the best hope for delaying or preventing the progression of CKD lies in a combined and multidisciplinary therapeutic approach, based on the existing evidence and acting on all these processes and pathways from the mechanistic point of view, and on a global process that is cardiovascular and renal risk to improve the prognosis of patients.

Understanding tubulointerstitial injury and repair mechanisms paves the way for renal outcome improvement in lupus nephritis / Entender la lesión tubulointersticial y los mecanismos de reparación será la vía para mejorar los desenlaces renales en nefritis lúpica

ABSTRACT Despite improvements in patient survival and quality of life, long-term renal survival has not changed significantly in the recent decades and nephritis relapses affect over 50% of patients with lupus nephritis. Renal fibrosis affecting the tubulointerstitial compartment is a central determinant of the prognosis of any kidney disease. Notwithstanding this evidence, the current 2003 ISN/RPS classification still focuses on glomerular pathology and does not include a mandatory score with clear subcategories of the tubulointerstitial injury in the biopsy. The pathogenesis, and the morphological and molecular characteristics of this process in patients with lupus nephritis will be considered, together with a discussion about the concepts the clinician needs to efficiently address in this injury during daily practice and in future clinical trials. Both tubulointerstitial inflammation and fibrosis are strongly correlated with poor renal outcomes in lupus nephritis, regardless of the extent of glomerular damage. Therefore, it is essential to develop reliable and noninvasive approaches to predict which patients are most likely to develop CKD so that appropriate interventions can be adopted before ESRD is established. Currently, no ideal method for monitoring kidney fibrosis exists, since repeated renal biopsies are invasive. Promising methods for assessing and monitoring fibrosis non-invasively include imaging techniques, such as magnetic resonance imaging or ex vivo confocal microscopy, integrated in computational and digital pathology techniques. Finally, beyond specific immunosuppressive treatment in Lupus Nephritis, identifying and treating cardiovascular risk factors should be a cornerstone of treatment in these patients.

RESUMEN A pesar de las mejoras en la sobrevida de los pacientes y su calidad de vida, la sobrevida renal en el largo plazo no ha cambiado significativamente durante las últimas décadas, y las recidivas nefríticas afectan a más del 50% de los pacientes con nefritis lúpica. La fibrosis renal, que afecta el compartimiento tubulointersticial, es un factor determinante central en el pronóstico de todas las patologías renales. A pesar de la evidencia, la actual clasificación ISN/RPS del 2003 todavía se concentra en la patología glomerular y no incluye un score obligatorio con claras subcategorías de la lesión tubulointersticial en la biopsia. Se hablará de la patogenia y las características morfológicas y moleculares de este proceso en pacientes con nefritis lúpica, así como de los conceptos que el clínico necesita para abordar esta lesión de manera eficiente en su práctica cotidiana y en los estudios clínicos a futuro. Tanto la inflamación tubulointersticial como la fibrosis se relacionan fuertemente con desenlaces renales pobres en la nefritis lúpica, con independencia de la extensión del dañío glomerular. Resulta por lo tanto esencial desarrollar sistemas confiables y no invasivos para predecir cuáles pacientes tendrán mayor probabilidad de desarrollar enfermedad renal crónica, a fin de realizar las intervenciones apropiadas antes de que se establezca la enfermedad renal terminal (ERT). En la actualidad, no existe un método ideal para monitorear la fibrosis renal, dado que las biopsias repetidas son procedimientos invasivos. Algunos de los métodos promisorios para evaluar y monitorear la fibrosis de manera no invasiva son las técnicas de imágenes, tales como la resonancia magnética o la microscopía confocal ex vivo, integradas en técnicas de patología computarizadas y digitales. Finalmente, más allá del tratamiento inmunosupresor específico para la nefritis lúpica, identificar y tratar los factores de riesgo cardiovascular deberá ser uno de los pilares de tratamiento en estos pacientes.

Silicosis in Artificial Quartz Conglomerate Workers. / Silicosis en trabajadores con conglomerados artificiales de cuarzo.

INTRODUCTION: Silicosis is a chronic progressive disease caused by inhalation of crystalline silica. Most cases develop in underground mine workers and in subjects involved in the extraction of natural stone (slate and granite). In view of the progressive emergence of new cases of silicosis in artificial quartz conglomerate workers, we performed a study to analyze the characteristics of silicosis produced by this new agent in Spain. METHODS: The study consisted of a series of 96 cases of silicosis diagnosed according to international criteria during the period 2010-2017. We analyzed clinical, radiological, pathological and functional characteristics. RESULTS: Mean age of participants was 45 years; 55% had simple silicosis and 45% had complicated silicosis. Ten patients were diagnosed with accelerated silicosis, with a mean age of 33 years. Mean time of exposure to conglomerates was 15 years, and 77% had not used appropriate protection measures. Half of the patients were asymptomatic and presented different classic forms on chest X-ray and chest high-resolution computed tomography, along with ground-glass images. No lung function changes were recorded. CONCLUSIONS: Silicosis in artificial quartz conglomerate workers occurs in a young, actively employed population, a considerable percentage of whom present an accelerated form. They have few symptoms and no functional limitations. Protection measures are scarce. It is important to characterize these features to provide early diagnosis and implement the necessary preventive measures.

Pulmonary cysts in smoking-related interstitial fibrosis: a form of pseudocyst secondary to pulmonary interstitial emphysema.

Smoking-related interstitial fibrosis is a distinct form of fibrosis, found in smokers, which has striking histopathological features. We present a case of pulmonary interstitial fibrosis with cysts in a 58-year-old woman who was a significant active smoker, presenting with a 7 month history of progressive dyspnea. TAC revealed thin-walled pulmonary cysts. An open lung biopsy was performed and the histopathological study showed hyaline fibrous thickening of the alveolar septa, respiratory bronchiolitis and cysts in the thickness of the interlobar septa. Immunohistochemically, the absence of an epithelial, vascular or lymphatic endothelial lining of the cysts would suggest that the cysts had been caused by pulmonary interstitial emphysema. Immunohistochemistry is essential in the differential diagnosis that includes, in this case, true cysts, pseudocysts and pulmonary lymphangiectasia.

Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type1 and transforming growth factor ß1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy. / Valor de los niveles urinarios de interleucina 6, factor de crecimiento epidérmico, proteína quimioatractante de monocitos de tipo 1 y factor de crecimiento transformante ß1 para la predicción de la extensión de las lesiones de fibrosis en biopsias de enfermos con nefropatía IgA.

OBJECTIVE: To analyse the associations between urinary levels of IL-6 EGF, MCP-1 and TGFß1 and clinical, biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and/or interstitial sclerosis. PATIENTS AND METHODS: A total of 58 patients with IgA nephropathy were studied. We determined the urine levels of IL-6, EGF, MCP-1, and TGFß1 at the time of diagnosis. The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria. We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions. RESULTS: IL-6, TGFß1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial, extracapillary or endocapillary proliferation. EGF showed a negative association with interstitial fibrosis. By categorising patients according to the Oxford classification, patients with T1 and T2 scores had significantly higher levels of IL-6, MCP-1, TGF-ß1 and significantly lower levels of EGF than patients with T0 scores. By multiple regression and logistic regression analyses, the levels of MCP-1, IL-6 and EGF were independent predictors of the fibrosis surface, after adjusting for age and eGFR. CONCLUSION: The urinary concentration of IL-6, EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy.