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- Title
Microangiopathic injury and augmented PAI-1 in human diabetic nephropathy.
- Authors
Paueksakon, Paisit; Revelo, Monica P; Ma, Li-Jun; Marcantoni, Carmelita; Fogo, Agnes B
- Abstract
Background. Microvascular injury and mesangial dysfunction contribute to the pathogenesis of diabetic glomerulosclerosis. We investigated the extent of microvascular injury characterized by fragmented red blood cells (RBCs) in the mesangium of glomeruli in diabetic nephropathy, and its clinicopathologic significance. We also investigated the possible contributions of plasminogen activator inhibitor-1 (PAI-1), which has been implicated in thrombosis and sclerosis, and the novel steroid receptor superfamily member, peroxisome proliferator-activated receptorγ (PPARγ), implicated in monocyte-foamy macrophage transformation in atherosclerosis and improved insulin responsiveness in diabetes. Methods. Sixty-four diabetic nephropathy (DN) cases in our renal biopsy files at VUMC, diagnosed between 1997 and 1999, were reviewed. Patients were classified based on the presence or absence of fragmented RBCs in the mesangium (M+, M-). PAI-1 and PPARγ immunostaining was performed with double staining for the macrophage marker CD68. Results. M+ lesions were present in 21.9% of cases, and in positive cases, involved on average 10.2 ± 2.1% of glomeruli. M+ patients were 40- to 78-years-old (mean SD ± 60.4 ± 9.8), the female/male ratio was 2.5, and the white/black ratio was 6. In M-, the patients' ages ranged from 29 to 81 years (57.6 ± 13.3, P = NS vs. M+), the female/male ratio was 0.5 (P < 0.05 vs. M+), and the white/black ratio was 2.3 (P = 0.1 vs. M+). Mean 24-hour urine protein in M+ was 9.9 ± 13.6 g/24 h, versus 4.0 ± 2.8 g/24 h in M - (P < 0.05). The fragmented RBCs in M+ cases localized exclusively within KimmelstielWilson nodules. PAI-1 and PPARγ immunostaining was increased in areas of sclerosis in arteries and glomeruli, with expression of both in glomerular mesangial, parietal and visceral epithelial cells. Infiltrating macrophages in glomeruli were PPARγ negative, contrasting positivity in...
- Subjects
DIABETIC nephropathies; MICROCIRCULATION disorders; PLASMINOGEN activators; CHEMICAL inhibitors
- Publication
Kidney International, 2002, Vol 61, Issue 6, p2142
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00384.x