Glomerular and Tubular Epithelial Defects in kd/kd Mice Lead to Progressive Renal Failure
| Autor: | Rexford S. Ahima, Min Peng, Wayne W. Hancock, Ray Meade, Daniel J. Rader, John E. Tomaszewski, Michael P. Madaio, David L. Gasser, Alberto Mendoza |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Pathology urogenital system Renal glomerulus business.industry Interstitial nephritis Glomerulosclerosis urologic and male genital diseases medicine.disease Podocyte Nephropathy Endocrinology medicine.anatomical_structure Nephrology Internal medicine medicine Albuminuria medicine.symptom business Nephrotic syndrome Nephritis |
| Zdroj: | American Journal of Nephrology. 25:604-610 |
| ISSN: | 1421-9670 0250-8095 |
| DOI: | 10.1159/000089709 |
| Popis: | Background/Aim: The kd/kd mouse spontaneously develops severe and progressive nephritis leading to renal failure, characterized by cellular infiltration, tubular destruction and glomerular sclerosis. Recent identification of the mutant gene and the observation that podocytes are affected, led to the hypothesis that there are primary renal epithelial cell defects in this strain. Methods: Clinical and pathological signs of disease in a large cohort of kd/kd mice were studied by light microscopy, electron microscopy, and biochemical analyses of serum and urine at early stages of disease. Special attention was paid to mice under 140 days of age that had normal blood urea nitrogen (BUN) levels, but had developed albuminuria. Results: Although overt glomerular abnormalities are commonly observed either coincident with or after tubulointerstitial nephritis, we now report that albuminuria and visceral epithelial abnormalities, including hyperplasia and podocyte effacement may occur before the onset of either elevated BUN levels or severe interstitial nephritis, and this is accompanied by biochemical perturbations in serum typical of the nephrotic syndrome. Conclusions: The results suggest that the defect in kd/kd mice primarily affects both the tubular and glomerular visceral epithelium. The tubular epithelial defect triggers autoimmune interstitial nephritis, whereas a defect in podocytes leads to proteinuria and glomerulosclerosis. Thus, a single mitochondrial abnormality may result in differences in disease expression that vary with the type of epithelial cells. It is likely that the mitochrondrial perturbations in glomerular and tubular epithelia act in concert, through activation of different pathologic pathways, to accelerate disease progression leading to renal failure. |
| Databáze: | OpenAIRE |
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