Selective distal nephron damage during isolated kidney perfusion

Abstract

The morphologic characteristics of the isolated perfused rat kidney were examined by light and electron microscopy. Following perfusion for 90 min, the cortex appeared normal except for the development of spaces in glomerular mesangial regions and ultrastructural abnormalities in very few proximal tubular cells. In the medulla, descending limbs of the loops of Henle and Collecting tubules appeared normal. During perfusion, however, even under optimal conditions, consistent and reproducible changes rapidly developed in cells of the thick ascending limb of Henle's loop, more specifically, in cells of the straight portion of the distal tubule in the inner stripe of the outer medulla. The changes became progressively more severe as perfusion continued and ranged from swelling of mitochondria at 15 min to complete cellular disruption by 90 min. Horseradish peroxidase added to the perfusion medium was found in and between damaged cells and in the interstitial tissue adjacent to affected areas. The pathogenesis of these selective medullary distal tubular abnormalities may relate to the specialized functional activity of this segment of the nephron. Such abnormalities may contribute to the specific functional defects of the preparation.

Vasopressin Stimulates Urinary Kallikrein Excretion in the Isolated Erythrocyte-Perfused Rat Kidney

“…In contrast, studies in the isolated kidney have demonstrated that kallikrein is released into the perfusate [9,32], In agree ment with these reports we have found that kallikrein is released into the perfusate of the isolated kidney. We have previously reported [33] that our erythrocyte perfused model is normal morphologically and does not devel op the nephronal injury which occurs in the isolated kidney perfused without red cells [34] , Therefore, our data support the view that kallikrein enters the perfusate by a phys iologic process rather than by the passive loss of the enzyme from injured cells. Release of kallikrein into the perfusate occurs at a con stant rate, equal approximately to 15% of the concurrent rate of urinary excretion.…”

Altered Distribution Pattern of Na+-K+-ATPase and Succinate Dehydrogenase Activities along the Nephron in Human Acute Post-Transplant Renal Failure

“…This "no-reflow" phenomenon has also been observed after renal ischaemia due to temporal renal artery occlusion (29). Apart from the existence of this phenomenon, cold ischaemia and reperfusion of the transplant per se could induce cellular energy depletion, particularly of the medullary thick ascending limbs of Henle's loop, äs demonstrated by Alcorn et al (30) in a normothermically perfused isolated kidney preparation. The measurement of the redox state of cytochrome aa 3 in such a preparation gave evidence of near-hypoxic conditions at this site of the nephron (31) due to circulatory conditions (32) and high transport activity (33).…”

Ischemia in the Isolated Erythrocyte-Perfused Rat Kidney

“…In the absence of erythro cytes, progressive damage to the mTAL occurs while the proximal tubules remain normal [2][3][4], The mTAL damage in this model has been shown to be due to oxygen deprivation resulting from the low oxygen carrying capacity of the cell-free perfusate [3. 4].…”

“…In the conventional isolated kidney per fused by a red cell-free medium, the medul lary thick ascending limb (mTAL) undergoes progressive damage during perfusion due to the low oxygen-carrying capacity of the per fusate [2][3][4], We have previously confirmed the finding of Brezis et al [5] that, when the isolated kidney is perfused by an erythrocyteenriched medium, the mTAL remains nor mal [4], Moreover, the isolated erythrocyteperfused kidney (IEPK) has hemodynamic characteristics comparable to those found in vivo, and manifests improved concentrating ability compared to the isolated kidney per fused with a red cell-free medium [6]. Thus the IEPK is a potentially attractive model for the study of renal ishemia.…”