Late Consequences of Acute Ischemic Injury to a Solitary... : Journal of the American Society of Nephrology (original) (raw)

Transplantation

PAGTALUNAN, MARIA ENRICA*; OLSON, JEAN L.†; TILNEY, NICHOLAS L.‡; MEYER, TIMOTHY W.*

*Departments of Medicine, Veterans Administration Palo Alto Health Care System and Stanford University, Palo Alto, California

†Department of Pathology, University of California, San Francisco, California

‡Surgical Research Laboratory and Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.

Correspondence to Dr. Timothy Meyer, Palo Alto Veterans Administration Medical Center, Nephrology 111R, 3801 Miranda Avenue, Palo Alto, CA 94303. Phone: 415-493-5000, extension 63314; Fax: 415-852-3411; E-mail: Meyer:[email protected]

Accepted August 7, 1998

Received April 24, 1998

Abstract

The sequelae of acute ischemic injury to a solitary kidney were assessed in rats subjected to right nephrectomy and transient occlusion of the left renal artery; control rats underwent right nephrectomy alone. Incomplete recovery from ischemic injury at 2 wk (serum creatinine levels of 1.1 ± 0.2 versus 0.5 ± 0.1 mg/dl, P < 0.05 for ischemia versus control) was followed by deterioration of renal function at 20 wk (serum creatinine levels of 1.7 ± 0.4 versus 0.7 ± 0.1 mg/dl, P < 0.05 for ischemia versus control). Morphologic studies showed that impairment of function after ischemic injury was associated with widespread tubulointerstitial disease. Some tubule segments were atrophic and others exhibited cystic dilation, so that the tubular cell volume fraction was reduced (37 ± 4 versus 53 ± 2%, P < 0.05), while the tubular lumen and interstitial volume fractions were increased (31 ± 4 versus 23 ± 2% and 29 ± 2 versus 20 ± 1%, respectively, both P < 0.05). Many glomeruli retained open capillary loops but were no longer connected to normal tubule segments (63 ± 8 versus 15 ± 7% of glomeruli, P < 0.05). There was a strong inverse correlation between the prevalence of such glomeruli and the GFR at 20 wk after ischemia (_r_2 = 0.79, P < 0.001). Tubulointerstitial disease at that time was accompanied by proteinuria and widespread segmental glomerular tuft injury. The occurrence of similar processes in human patients could contribute to the loss of graft kidneys that suffer ischemic injury during transplantation.