Erythrocytes alter the pattern of renal hypoxic injury: predominance of proximal tubular injury with moderate hypoxia

Abstract

1. The distribution of morphological injury was assessed qualitatively and quantitatively in the perfused rat kidney in vitro at controlled rates of oxygen delivery in the presence of low concentrations of erythrocytes. 2. In control kidneys (total oxygen delivery approximately 32 μmol/min per kidney) no injury was seen in the medullary thick ascending limb of Henle's loop (MTAL) whilst 11 ± 5 (sd)% of proximal tubules sustained damage. 3. Mild hypoxia (total oxygen delivery approximately 28 μmol/min per kidney) produced little or no injury to MTAL, namely 6 ± 4(sd)% and 3 ± 3% of tubules damaged, respectively. In contrast, both groups sustained extensive damage to proximal tubules, averaging 46 ± 13% (P < 0.01 vs control) and 84 ± 14% (P < 0.001 vs control), respectively. This damage was equally distributed between the superficial and deep cortex. 4. Comparison with morphometric data obtained previously from cell-free-perfused rat kidneys [P. J. Ratcliffe, Z. H. Endre, S. J. Scheinman, J. D. Tange, J. G. G. Ledingham & G. K. Radda (1988) Clinical Science74, 437–448] showed that (a) erythrocytes prevent hypoxic damage to the MTAL at mild and moderate levels of hypoxia; (b) when oxygen delivery rates are matched between cell-free- and erythrocyte-perfused kidneys, proximal tubular injury is greater in the presence of erythrocytes; (c) when arterial partial pressure of oxygen is matched between cell-free- and erythrocyte-perfused kidneys, the degree of proximal tubular injury is similar. 5. The data suggest that the proximal tubule and not the MTAL is the nephron segment most at risk of hypoxic injury in vitro.

Ischaemic Acute Renal Failure: Why Does It Occur?

“…Firstly, in vivo, oxygen is carried as oxyhaemoglobin, and it may be that the predisposition of the cell-free perfused kidney to mTAL damage is dependent on increased shunt diffusion in the renal medulla when oxygen is delivered entirely in a physically dissolved form. This possibility is supported by our finding that when perfusate is supplemented with erythrocytes at a haematocrit of 2-4% the distribution of hypoxic damage is strikingly altered so that the proximal tubule rather than the mTAL is now most susceptible to damage [20]. Even so, in both these perfused kidney models regional hypoxic injury occurs well in advance of a severe reduc tion in total oxygen delivery.…”

23Na‐NMR detects hypoxic injury in intact kidney: Increases in sodium inhibited by DMSO and DMTU

“…Along with other groups (8,9), we have demonstrated (2,10) that graded hypoxia in the IPRK is a useful model for studying hypoxic injury in experimental ARF. In this model the changes in ATP and the fractional excretion of sodium (FEN,) are closely correlated with oxygen delivery and with the extent of morphological injury to renal tubules, specifically to proximal tubules and medullary thick ascending limbs of Henle's loops.…”

“…In addition, unperfused control kidneys were obtained for some assays by rapidly freeze-clamping unperfused left and right kidneys (n = 5). For the measurement of metabolites of lipid peroxidation, frozen tissue was weighed and homogenized at high-speed in 10 volumes of cold 0.015 M phosphate buffer, pH 7.4, before processing for assmay of the individual metabolites. For adenine nucleotide and total glutathione measurements, kidney tissue was pulverized in liquid nitrogen and extracted into 0.02 M HC1 in methanol at -30°C as described by Lowry and Passonneau (15).…”

Anemia Induces 5’-Nucleotidase in Fibroblasts of Cortical Labyrinth of Rat Kidney

“…This would affect the metabo lism of adenine nucleotides. Actually, the fol lowing data from the literature suggest that, despite the small arteriovenous difference of oxygen tension, the energy balance of some, probably tubular, cell types in the kidney is affected by changes of the oxygen transport capacity of blood: the oxidative metabolism of some structures in the kidney appear to be limited by oxygen availability even under con ditions of normal oxygen supply [11][12][13][ and moderate decreases in oxygen supply lead to decreased content of renal ATP [14]. The stim ulus for secretion of erythropoietin in the kid ney seems to depend in some way on transport work in the proximal tubule [15].…”