Table 2.

Segmental proximal tubular function and response to injury: mechanisms

Function	Glomerulo-Tubular Junction	S1	S2, S3	Proximal Tubule Energy
Normal	Site of reabsorption of amino acids, glucose, bicarbonate; lacks peroxisomes (87)		Peroxisomes (87)	Proximal tubule ATP > distal tubule energy consumption (156); Glycolysis (neonate) → oxidative metabolism (adult) (35)
Response to stress (AKI): Ischemia/reperfusion; metabolic injury; hypoxia; toxins; sepsis	Autophagy, apoptosis → ATG	Fanconi syndrome; “sensor” of stressors in AKI: signals S2 and S3 responses (39); ↑sirtuin and HO-1 (antioxidants) (87); ↑urinary retinol binding protein (34)	↑TGF-β; apoptosis, necrosis (39)	↓oxidative metabolism; ↑IF1 (endogenous inhibitor of mitochondrial ATPase) (74)
Regenerative response	Tubular progenitor cells seal urinary pole →ATG (48)	Cytoresistance to subsequent insults (194); cells in G1 phase ready to proliferate in response to stress (179); regeneration capacity is limited: AKI → proximal tubule shortening (162)

Nos. in parentheses, reference nos.

AKI, acute kidney injury; ATG, atubular glomeruli; HO-1, heme oxygenase-1; IF1, ATPase inhibitory factor 1; TGF-β, transforming growth factor-β.