Postischemic injury, delayed function and Na+/K(+)-ATPase distribution in the transplanted kidney.
We evaluated the postischemic renal injury in 22 patients undergoing renal transplantation. Renal tissue obtained 45 to 60 minutes after reperfusion of the allograft was stained with specific antibodies against the delta subunit of Na+/K(+)-ATPase, fodrin and ankyrin. The distribution of each cytoskeletal protein was analyzed by laser confocal microscopy. Subsequent allograft function was assessed on two occasions, 1 to 3 and 36 hours post-reperfusion, respectively. Recipients were divided into two groups: those who achieved a normal GFR on post-transplant day 3 (group 1, N = 12) and those with persistent hypofiltration (group 2, N = 10). Patients of both groups exhibited impaired sodium reabsorption and isosthenuria one to three hours postoperatively, but these abnormalities persisted on day 3 only in group 2 subjects with persistent hypofiltration. Abnormalities of Na+/K(+)-ATPase, ankyrin and fodrin were confined to proximal tubule cells and were marked only in the subjects of group 2. They consisted of redistribution of each cytoskeletal protein from the basolateral membrane to the cytoplasm. We conclude that postischemic injury to a renal allograft results in a loss of polarity of proximal tubule cells. We propose that ensuing impairment of proximal sodium reabsorption could activate tubuloglomerular feedback, thereby contributing to the protracted hypofiltration that characterizes this form of postischemic, acute renal failure.
Alejandro
V S
VS
Department of Molecular and Cellular Physiology, Standford University School of Medicine, California, USA.
Nelson
W J
WJ
Huie
P
P
Sibley
R K
RK
Dafoe
D
D
Kuo
P
P
Scandling
J D
JD
Myers
B D
BD
D000293:Adolescent; D000328:Adult; D000368:Aged; D017487:Ankyrins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D015427:Reperfusion Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors; D013049:Spectrin
D017487:Ankyrins; D002352:Carrier Proteins; D008840:Microfilament Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D013049:Spectrin