BackgroundNephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease.MethodsTo determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6–12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria.ResultsAmong 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m2), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence.ConclusionsAfter a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.
Background Chronic tubulointerstitial injury on kidney biopsy is usually quantified by the percentage of cortex with interstitial fibrosis/tubular atrophy (IF/TA). Whether other patterns of IF/TA or inflammation in the tubulointerstitium have prognostic importance beyond percentage IF/TA is unclear.
Methods We obtained, stained, and digitally scanned full cortical thickness wedge sections of renal parenchyma from patients who underwent a radical nephrectomy for tumor in 2000 to 2015 and morphometrically analyzed the tubulointerstitium of the cortex for percentage IF/TA, IF/TA density (foci per mm2 cortex), percentage subcapsular IF/TA, striped IF/TA, percentage inflammation (both within and outside IF/TA regions), and percentage subcapsular inflammation. Patients were followed with visits every 6-12 months. Progressive chronic kidney disease (CKD) was defined as dialysis, kidney transplantation, or 40% decline from the postnephrectomy estimated glomerular filtration rate (eGFR). Cox models assessed risk of CKD or noncancer mortality with morphometric measures of tubulointerstitial injury after adjustment for percentage IF/TA and clinical characteristics.
Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73m2), 117 progressive CKD events and 183 noncancer deaths occurred over a median 6.4 years. Higher IF/TA density predicted both progressive CKD and noncancer mortality after adjustment for percentage IF/TA and predicted progressive CKD after further adjustment for clinical characteristics. Independent of percentage IF/TA, age, and sex, higher IF/TA density correlated with lower eGFR, smaller nonsclerosed glomeruli, more global glomerulosclerosis, and smaller total cortical volume.
Conclusions Higher density of IF/TA foci (a more scattered pattern with more and smaller foci) predicts higher risk of progressive CKD after radical nephrectomy compared with the same percentage of IF/TA but with fewer and larger foci.
INTRODUCTION: To describe the clinical, endoscopic, and histopathology features of esophageal graft-vs-host disease (GVHD).
METHODS:Patients with biopsy-proven esophageal GVHD diagnosed at Mayo Clinic between 2000 and 2021 were included.
RESULTS:In 43 esophageal patients, other organ GVHD was present in 58% before and 86% at esophageal GVHD diagnosis. Esophageal specific symptoms were uncommon (dysphagia 26% and odynophagia/heartburn 5%). Esophagogastroduodenoscopy was abnormal in 72% patients demonstrating erosive esophagitis, ulceration, desquamation, or rings/furrows in a diffuse or focal pattern.DISCUSSION:There should be a low threshold for esophageal biopsies for GVHD because esophageal symptoms and endoscopic findings may be nonspecific or absent.
Los avances en el ámbito de la patología y cirugía realizados entre 1500 y 1750 sirvieron como base para su desarrollo en los siglos XVIII y XIX, comprendiendo la naturaleza y composición macroscópica y microscópica de los tumores benignos y malignos. Desde entonces, los conceptos se volvieron a enfocar desde el órgano al tejido y a la célula, afectando el nacimiento de la histopatología que ha dominado esta ciencia durante siglo y medio. Luego, cuando el segundo milenio se acercaba a su fin, nuevas y poderosas tecnologías comenzaron a forzar una nueva revisión de las ideas alrededor de la patología convencional, desde las enfermedades basadas en alteraciones celulares hacia las enfermedades basadas en genes, pasando por el estudio de moléculas individuales y su interacción. El auge de la medicina de precisión comenzó en la década de 1980 con el desarrollo de la inmunohistoquímica. Este método permitió a los patólogos investigar rápidamente la expresión de proteínas en piezas obtenidas de muestras quirúrgicas. Estos niveles de expresión pronto serían relevantes para las subclasificaciones de los tumores que no eran accesibles por la microscopía óptica clásica. Recientemente, la introducción de la patología molecular tuvo un impacto positivo en el manejo de los pacientes con cáncer, especialmente para seleccionar terapias dirigidas y permitir el uso de técnicas como las biopsias líquidas que establecieron un nuevo estándar para los regímenes de monitorización continua durante el curso de la enfermedad. Esta técnica permite la detección de las recurrencias de la enfermedad antes que la radiología, lo que permite adaptar las terapias con anticipación. Además, también puede detectarse el desarrollo de mutaciones somáticas asociadas con la resistencia a las intervenciones realizadas.
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