Table 1.
Segmental proximal tubular function and response to injury: animal models and human diseases
| Model/Disease | Glomerulotubular Junction Response To Injury | Proximal Tubule | Proximal Tubule Energy |
|---|---|---|---|
| Renal ablation | ATG early (58) | Progressive proximal tubular atrophy → ↑ ATG from 9 to 48%, 10–25 wk after 5/6 nephrectomy | ↑Qo2, early (121) |
| Unilateral ureteral obstruction | ATG early (50) | Oxidative stress and cell death by autophagy, apoptosis, necrosis | ↓Qo2, ↑glycolysis (158) |
| Polycystic kidney disease | ATG late (56) | Oxidative stress and cell death | |
| Congenital nephrotic syndrome | ATG early (176) | Protein overload proximal tubule injury | |
| Cystinosis | ATG late (55, 97) | Swan neck. Mitoquinone protective (antioxidant) (55) | ↓mitochondria (55) |
| Diabetes | Type 1 → ATG early (117) | 71% GTJ abnormalities in proteinuric type 1 diabetics | ↑catalase protective in mouse (14), mitochondrial uncoupling and ↑Qo2 →hypoxia (52) |
| Type 2 → ATG late (186) | 44% GTJ abnormalities in type 2 diabetic patients with low proteinuria | ||
| Renal artery stenosis | Mild-reversible (73) | Tubular atrophy and thickened TBM reverse with unclipping and stopping ACE inhibitor (73) | ↓mitochondria |
| ↓Na-K-ATPase | |||
| severe → ATG late (110) | 52% ATG, 40% glomeruli connected to atrophic tubules; normal number of glomeruli (110) | ||
| Chronic allograft rejection | ATG late | 18% ATG 7 yr posttransplant (133) | Rat renal transplant → mitochondrial uncoupling, ↑Qo2 → hypoxia (134) |
Nos. in parentheses, reference nos.
ATG, atubular glomeruli; GTJ, glomerulotubular junction; TBM, tubular basement membrane; ACE, angiotensin-converting enzyme; Qo2, oxygen consumption.