Table 1.
Commonly accepted criteria for hypertensive glomerulopathy assessment enable quantification and comparison among human studies.
Table 2.
Variable parameters for hypertensive glomerulopathy assessment unable quantification and comparison among animal studies.
Table 3.
Characteristics of the animals at the end of the study.
Fig 1.
Criteria for hypertensive glomerulopathy in humans.
A, D. Normal glomerulus. B In solidified glomeruli, mesangial widening results in prominent hyalinotic lesions and segmental sclerosis extending to Bowman’s capsule. Podocytes, mesangial and endothelial cells, capillary lumens gradually disappeared within expanding hyalinotic segments. C In ischemic glomeruli, the tuft retracted, capillary walls thickened while their lumens collapsed; hyalinosis and segmental sclerosis are less prominent. E, F Either solidified or ischemic glomeruli progress into the globally sclerotic lesion–acellular collagenous tufts. A—C, E–periodic acid–Schiff; D, F–Masson trichrome staining. x600.
Fig 2.
Representative images of hypertensive glomerulopathy in mouse models.
A, D Normal mouse glomerulus. B, E Angiotensin II infused mice. Diminished glomeruli contain abundant mesangial cells, expanded mesangial matrix, and reduced capillary lumens. Prominent mesangial expansion has mild fibrotic component: Collagen staining increased along the glomerular basement membrane. C, F Glomeruli in the renin overexpressing mice appear unremarkable. Hyalinosis and focal segmental glomerulosclerosis was absent in both models. A-C–periodic acid-Schiff; D-F—Masson trichrome staining. x600.
Fig 3.
Glomerular lesions in hypertensive animal models were much lower compared to humans.
A Frequency of hyalinosis/focal segmental glomerulosclerosis is presented as the percentage of positively stained tufts. Among samples, only the clipped kidney (2K1C-clp) demonstrated lesions (⋇ P<0.01 vs control) that remarkably lower than human values (# P < 0.0001 vs 2K1C-clp). B Morphometric data of the mesangial, capillary and glomerular volumes. The whole bar represents the glomerular volume as the sum of the mesangial (black part) and capillary (white part) volumes. P < 0.01 vs control for mesangium (⋇), capillary (#), and glomerular (§) volumes respectively. C Mesangial cellularity markedly increased in angiotensin II infused mice (Ang II) and decreased in spontaneously hypertensive rats (SHR) (⋇ P < 0.001 vs control) but still far from hypocellularity observed in human glomerulosclerosis (# P < 0.001 vs SHR). D The collagen-positive area in glomeruli. P < 0.001 vs control (⋇). TTRhRen—renin overexpressing mice; 2K1C-nclp—non-clipped kidneys. Human data are reference values from Table 1. E Genetic models of hypertension demonstrated lower number of nephrons. P < 0.01 vs control (⋇). Each column consists of mean ± SEM.
Fig 4.
Representative images of hypertensive glomerulopathy in rats.
A, D Control rats. B, E Spontaneously hypertensive rats. Hypertrophic glomeruli are distinguished with numerous enlarged capillary lumens. C, F The nonclipped kidney. Hypertrophic glomeruli had no visible lesions except enlarged capillary loops and more collagen that distributed along the glomerular basement membrane. Hyalinosis and segmental sclerosis was absent in all models. A-C—periodic acid-Schiff; D-F Masson trichrome staining. x600.
Fig 5.
Hypertensive glomerulopathy in the clipped kidney resembled human glomerulosclerosis.
A, D Control rats. B, C, E, F Tufts showed features of the ischemic glomeruli, including reduced capillary lumens, retracted tufts, narrowed Bowman’s spaces, PAS filled mesangium with small collagen amount. A-C—periodic acid-Schiff; D-F—Masson trichrome staining. x600.
Fig 6.
Detailed histopathological features in hypertensive animals.
A Only few solidified glomeruli with hyalinosis were found through all scanned sections in the non-clipped kidneys. B, C Classical human-like focal segmental glomerulosclerosis in solidified glomeruli was more frequently detected in renin overexpressing mice with streptozotocin-induced diabetes [92]. Total karyorrhexis (arrows) and mature collagen in globally sclerotic glomeruli was easily found reflecting irreversible glomerular damage. A, B—periodic acid-Schiff; C—Masson trichrome staining. x600.