Acute kidney injury in the diabetic rat: studies in the isolated perfused and intact kidney.
OBJECTIVE
Diabetes leads to chronic renal hypoxia and cellular hypoxia response (mediated by hypoxia-inducible factors) and predisposes to acute kidney injury. We studied the impact of acute and chronic hypoxic stress on the development of acute kidney injury in the diabetic rat kidney.


METHODS
Control (CTR) and streptozotocin (STZ)-diabetic rats were studied following acute medullary hypoxic stress, induced by combinations of radiocontrast and inhibitors of cyclooxygenase and NO synthase. In addition, STZ and CTR kidneys were compared following ex vivo perfusion with oxygenated cell-free medium.


RESULTS
The extents of medullary acute tubular injury and renal dysfunction were largely comparable in CTR and STZ-diabetic kidneys in vivo. By contrast, functional deterioration and outer medullary injury were markedly enhanced in STZ kidneys perfused ex vivo. A peculiar collecting duct injury pattern, with cell swelling and detachment, noted in intact STZ kidneys, prominently intensified following isolated perfusion.


CONCLUSIONS
The diabetic kidney is remarkably resistant to acute hypoxic injury in vivo, possibly due to chronic hypoxia adaptation. Thus, though diabetes predisposes to acute kidney injury in various clinical settings, reduced kidney function does not necessarily imply a greater extent of true tubular damage. The collecting duct injury pattern is an as yet unrecognized feature of early experimental diabetes.
Rosenberger
Christian
C
Department of Nephrology and Medical Intensive Care, Charité University Clinic, Berlin, Germany.
Khamaisi
Mogher
M
Goldfarb
Marina
M
Shina
Ahuva
A
Shilo
Vitali
V
Zilbertrest
Fanni
F
Rosen
Seymour
S
Heyman
Samuel N
SN
D000818:Animals; D015687:Cell Hypoxia; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology