Glomerular permeability and polyanion in Adriamycin nephrosis in the rat

Glomerular permeability and polyanion in Adriamycin nephrosis in the rat. Alterations in glomerular permeability were studied in Adriamycin-induced proteinuria in rats by measuring fractional clearances (C/GFR) of uncharged labeled dextrans of varying molecular radii (ae) and of anionic, native, and cationic horseradish peroxidases (HRP) in experimental and control animals. Experimental animals were studied between days 14 and 55 after a single intravenous dose of Adriamycin (doxorubicin), 7.5 mg/kg. Mean proteinuria in the experimental animals was 98mg/24hr. Glomerular morphology showed few changes except for epithelial cell swelling, vacuolization, and foot process obliteration, and a significant reduction of glomerular colloidal iron staining. Polyethyleneimine staining revealed a similar distribution of anionic sites in the laminae rarae interna and externa in proteinuric rats as compared with controls. Inulin clearances revealed reduction in GFR and RPF of 20 and 15%, respectively. Dextran C/GFR values showed in experimental animals a size defect for molecules with an ae exceeding 40 Å, with a four- to fivefold increase over the values found in control animals for dextrans with ae of 58 and 60 Å. The peroxidase clearances showed a slight increase in C/GFR of anionic HRP in experimental animals, as could be expected on the basis of the sieving defect, whereas the C/GFR values for native and cationic HRP were virtually unchanged, indicating an intact functional charge barrier in the proteinuric animals. The results indicate that proteinuria in this model, which morphologically resembles aminonucleoside nephrosis, is due to a sieving defect, the charge barrier being functionally intact. The results further suggest, at least in this model, that a reduction in colloidal iron reactive glomerular polyanion is not associated with a defect in the charge selective barrier function.Perméabilité glomérulaire et polyanions dans la néphrose par Adriamycine chez le rat. Les altérations de la perméabilité glomérulaire ont été édutiées chez le rat au cours de la protéinurie induite par l'adriamycine en mesurant les clearances fractionnelles (C/GFR) de dextrans neutres marqués de différents rayons moléculaires (ae), et de peroxydases de raifort anioniques, neutres, et cationiques (HRP) chez des animaux expérimentaux et contrôles. Les animaux expérimentaux étaient étudiés entre les jours 14 et 55 après une injection unique intra-veineuse d'Adriamycine (doxorubicine), 7.5mg/kg. La protéinurie moyenne chez les animaux expérimentaux était de 98mg/24hr. La morphologie glomérulaire indiquait peu de modifications excepté un gonflement des cellules épithéliales, une vacuolisation et une fusion des pédicelles, et une réduction significative de la coloration glomérulaire par le fer colloïdal. La coloration au polyéthylèneimine a révélé une distribution identique des sites anioniques dans les lamina rarae interna et externa de rats protéinuriques par rapport aux contrôles. Les clearances de l'inuline ont montré une réduction de GFR et RPF de 20 et 15%, respectivement. Les valeurs de C/GFR du dextran ont indiqué chez les animaux expérimentaux un trouble portant sur la taille pour les molécules dont ae dépasse 40 Å, avec une augmentation de quatre- à cinqfois au-dessus des valeurs trouvées chez les animaux contrôles pour des dextrans d'ae de 58 et 60 Å. Les clearances des peroxydases ont indiqué une augmentation modérée de C/GRF pour HRP anionique chez les animaux expérimentaux, comme cela était attendu sur la base d'un trouble de la filtration, tandis que les valeurs de C/GFR pour les HRP natives et cationiques étaient virtuellement inchangées, indiquant une barrière fonctionnelle de charge intacte chez les animaux protéinuriques. Ces résultats indiquent que la protéinurie dans ce modèle qui ressemble morphologiquement à la néphrose des aminonucléosides, est due à un trouble de la filtration, la barrière de charges restant fonctionnellement intacte. Ces résultats suggèrent en outre, au moins dans ce modèle, que une réduction des polyanions glomérulaires réagissant avec le fer colloïdal n'est pas associée à une anomalie de la barrière sélective aux charges

Deposition of the membrane attack complex in healthy and diseased human kidneys

The membrane attack complex-also known as C5b-9-is the end-product of the classical, lectin, and alternative complement pathways. It is thought to play an important role in the pathogenesis of various kidney diseases by causing cellular injury and tissue inflammation, resulting in sclerosis and fibrosis. These deleterious effects are, consequently, targeted in the development of novel therapies that inhibit the formation of C5b-9, such as eculizumab. To clarify how C5b-9 contributes to kidney disease and to predict which patients benefit from such therapy, knowledge on deposition of C5b-9 in the kidney is essential. Because immunohistochemical staining of C5b-9 has not been routinely conducted and never been compared across studies, we provide a review of studies on deposition of C5b-9 in healthy and diseased human kidneys. We describe techniques to stain deposits and compare the occurrence of deposits in healthy kidneys and in a wide spectrum of kidney diseases, including hypertensive nephropathy, diabetic nephropathy, membranous nephropathy, IgA nephropathy, lupus nephritis, C3 glomerulopathy, and thrombotic microangiopathies such as the atypical hemolytic uremic syndrome, vasculitis, interstitial nephritis, acute tubular necrosis, kidney tumors, and rejection of kidney transplants. We summarize how these deposits are related with other histological lesions and clinical characteristics. We evaluate the prognostic relevance of these deposits in the light of possible treatment with complement inhibitors.Nephrolog

A proposal for standardized grading of chronic changes in native kidney biopsy specimens

IP1BImmunopathology of vascular and renal diseases and of organ and celltransplantatio

Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN

Immunopathology of vascular and renal diseases and of organ and celltransplantationIP1