Effects of short-term hypothermic perfusion and cold storage on function of the isolated-perfused dog kidney

The isolated-perfused dog kidney was used as a model to measure the effects of short-term hypothermic preservation on renal function and metabolism. Kidneys were cold-stored in Collins' solution, hypotonic citrate, or phosphate-buffered sucrose for 4 and 24 hr, or were continuously perfused for 4 and 24 hr with a synthetic perfusate. Following preservation kidneys were perfused with an albumin-containing perfusate at 37 degrees C for 60 min for determination of renal function. The results indicate that many of the effects of short-term preservation on renal function in dog kidneys are similar to results reported for rat and rabbit kidneys. Cold storage for 4 hr resulted in a large decrease in GFR (57%), but only a small decrease in Na reabsorption (from 97 to 87%). Cold storage for 24 hr caused a further decline in renal function (GFR = 95% decrease, Na reabsorption = 49-64%). Results were similar for all cold storage solutions tested. Perfusion for 4 hr was less damaging to renal function than cold storage. The GFR decreased only 14% and urine formation and Na reabsorption were practically normal. After 24 hr of hypothermic perfusion, the GFR was reduced by 79%, urine flow was normal, and Na reabsorption was 78%. There were no obvious biochemical correlates (adenine nucleotides, tissue edema, or electrolyte concentration) with the loss of renal function during short-term preservation. The results suggest that the isolated-perfused dog kidney can be used to test the effects of preservation on renal function, and yields results similar to those obtained using small animal models.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preservation of renal function by adenosine-stimulated ATP synthesis in hypothermically perfused dog kidneys

Dog kidneys were hypothermically perfused for 1 to 5 days in the presence or absence of adenosine (5 mM). Following 1, 3, and 5 days, kidneys were reperfused at normothermia in an isolated perfusion system using a bovine serum albumin containing perfusate and renal function was determined. At the end of normothermic perfusion, kidney cortical slices were removed for biochemical analysis. Kidneys preserved in the presence of adenosine generated much higher concentrations of ATP during normothermic perfusion than kidneys preserved in the absence of adenosine at all time periods studied. In kidneys reperfused (37 degrees C) after 3 days of preservation, the ATP concentration averaged 9.15 mumol/g dry wt (+adenosine) vs. 4.75 mumol/g dry wt (-adenosine). After 5 days, the average was 12.65 mumol/g dry wt (+adenosine) vs. 4.00 mumol/g dry wt (-adenosine). The tissue concentration of K+ was higher in kidneys perfused in the presence of adenosine for all time periods studied. The presence of adenosine had little effect on the GFR (creatinine clearance) which was reduced by about 90% from control values at both 3 and 5 days of preservation. The primary effect of adenosine on renal function was a greater preservation of the capability of the isolated perfused kidney to reabsorb Na+ from the glomerular filtrate. In the absence of adenosine Na+ reabsorption was reduced from 97 to 50% whereas in the presence of adenosine was reduced to only 80% after 3 days of preservation. After 5 days of perfusion Na+ reabsorption was unaffected by the presence of adenosine and the amount resorbed was only 25-30% of the amount filtered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of effect on human lipoprotein-triacylglycerol on the function of perfused rat kidney

We determined whether addition of human lipoprotein-TG to the perfusate for the isolated rat kidney would increase net Na+ reabsorption or maintain renal tissue K+ content. Rat kidneys (n = 6) were perfused for 75 min with a perfusate containing 6 g% of substrate-free albumin in Krebs-Ringer bicarbonate and a mixture of human chylomicrons and very low density lipoproteins (human lipoprotein-triacylglycerol (HL-TG]. Control kidneys (n = 6) were perfused in the substrate-limited state, i.e., without any exogenous substrates added to the perfusate. Means (n = 6) for function of control kidneys were GFR = 808 +/- 50 microliter g-1 X min-1; %T-Na+ = 63.3 +/- 1.3%. A significant loss of tissue K+ occurred: tissue K+ remaining after 75 min of perfusion = 79.1 +/- 1.9%. Although kidney tissue contains lipoprotein lipase, HL-TG (n = 6) did not increase %Na+ reabsorption (64.3 +/- 2.6%) or maintain tissue K+ content (80.6 +/- 2.0%). Therefore, the TG might have been hydrolyzed and taken up for biosynthesis, the rat kidney lipoprotein lipase might have been inactive, or the rat kidney might not use lipoprotein-TG for biosynthesis or oxidation.     

Lidocaine-containing Euro-Collins solution prevents renal injury in the isolated perfused canine kidney exposed to prolonged cold ischemia

Previous studies have reported a decreased incidence of delayed graft function after cadaveric transplantation with the use of lidocaine pretreatment of the donor. We evaluated the effects of lidocaine on prolonged cold ischemia and reperfusion injury in a canine model of isolated kidney perfusion (IPK). The purpose of this study was to evaluate the renal function of isolated perfused canine kidneys after 48 h of cold storage with Euro-Collins (EC) solution or EC solution plus lidocaine. Isolated perfused canine kidneys were randomized into four groups which contained six kidneys: I) cold flush with EC solution and immediately reperfused, II) cold flush with EC solution plus lidocaine and immediately reperfused, III) 48 h of cold storage with EC and reperfusion, IV) 48 h of cold storage with EC solution plus lidocaine and reperfusion. The measured renal functions were glomerular filtration rate, urine production, perfusate flow, urinary lactic dehydrogenase (ULDH), Na reabsorptive capacity, and tissue MDA levels. Histological examination was performed after reperfusion. The tubular functions of kidneys preserved with EC solution containing lidocaine were better when compared with the kidneys preserved with EC alone. Tubular injury marker levels (ULDH) in group IV were significantly lower than in group III and lidocaine also reduced lipid peroxidation during reperfusion. This is in agreement with the histological results. The results of the present study can be taken as evidence of the cytoprotective effect of lidocaine, which may therefore be accepted as a useful agent for kidney preservation.     

Mechanisms of the early and late response of the kidney to contralateral nephrectomy.

The immediate (1 day, D1) and late (90 days, D90) effects of unilateral nephrectomy on contralateral renal hemodynamics, and the renal handling of electrolytes and water were investigated in the whole animal. The immediate and late ability of the remnant kidney to autoregulate perfusate flow and glomerular filtration rate (GFR) was studied in the isolated perfused kidney of the rat. In the whole animal, in D1 rats as compared to controls, GFR calculated for a single kidney increased from 0.85 +/- 0.3 to 1.1 +/- 0.2 ml/min (p less than 0.05). In D90 rats GFR increased further and was similar to prenephrectomy GFR (1.4 +/- 0.5 vs. 1.7 +/- 0.5 ml/min, p NS). Urinary prostanoid excretion in 24 h, calculated for one kidney, increased by 50-500% in D1 rats, but returned to prenephrectomy values in D90 rats. In the isolated perfused kidney, decreasing perfusion pressure (PP) from 100 to 70 mmHg did not change the renal vascular resistance (RVR) in control and D90 kidneys, but in D1 kidneys RVR decreased from 8.6 +/- 1.3 to 7 +/- 1.3 mm Hg/ml/min (p less than 0.05). In D90 kidneys RVR was significantly lower as compared to control and D1 kidneys at all perfusion pressures. Decreasing PP from 100 to 70 mm Hg resulted in a significant decrease in perfusion flow in control, D1 and D90 kidneys, while with the increase in PP from 100 to 130 mm Hg the perfusion flow increased significantly in all three kidney groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rabbit kidney function in vitro: the effect of colloids, energy substrate, a vasodilator, perfusion pressure, and bovine serum albumin

An in vitro perfusion system at 37 degrees C for the assessment of rabbit kidney function is described. The purpose of this assay system is to evaluate the effects of cryobiological manipulation on kidney function. The effect of the colloids dextran (MW = 70,000, 80,000, and 180,000) in the perfusate at 110 mm Hg were compared to a reduced perfusion pressure, colloid-free perfusate. Better function was obtained at lower perfusion pressure with the colloid-free perfusate. Less damage was noted histologically on light and electron microscopy. Investigation of energy substrates on rabbit kidney function demonstrated that butyrate, or lactate, in addition to glucose resulted in increased sodium and glucose reabsorption over glucose alone. Substrate-free perfused kidneys exhibited depressed Na transport. Lactate, and to some extent butyrate, decreased net glucose utilization. An alpha-adrenergic blocking agent, isoxsuprine, in the initial flush solution did not appear to be beneficial. An increase of perfusion pressure from 50 to 75 mm Hg resulted in an increase in GFR. Tubular function was enhanced by inclusion of small amounts of BSA in the perfusate.     

Multinuclear NMR studies of intracellular cations in perfused hypertensive rat kidney.

We have investigated hypertension-associated alterations in intracellular cations in the kidney by measuring intracellular pH, free Mg2+, free Ca2+, and Na+ concentrations in perfused normotensive and hypertensive rat (8-14 weeks old) kidneys using 31P, 19F, and double quantum-filtered (DQ) 23Na NMR. The effects of both anoxia and ischemia on the 23Na DQ signal confirmed its ability to detect changes in intracellular Na+. However, there was a sizable contribution of the extracellular Na+ to the 23Na DQ signal of the kidney. The intracellular free Ca2+ concentration, measured using 19F NMR and 5,5'difluoro-1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid, also increased dramatically during ischemia; the increase could be partly reversed by reperfusion. No significant differences were found between normotensive and hypertensive kidneys in the ATP level, intracellular pH, intracellular free Mg2+, and the 23Na DQ signal or in the extent of the extracellular contribution to the 23Na DQ signal. Oxygen consumption rates were also similar for the normotensive (5.02 +/- 0.46 mumol of O2/min/g) and hypertensive (5.47 +/- 0.42 mumol O2/min/g) rat kidneys. The absence of a significant difference in intracellular pH, Na+ concentration, and oxygen consumption between normotensive and hypertensive rat kidneys suggests that an alteration in the luminal Na+/H+ antiport activity in hypertension is unlikely. However, a highly significant increase (64%, p less than 0.01) in free Ca2+ concentration was found in perfused kidneys from hypertensive rats (557 +/- 48 nM, blood pressure = 199 +/- 5 mmHg, n = 6) compared with normotensive rats (339 +/- 21 nM, blood pressure = 134 +/- 6, n = 4) indicating altered renal calcium homeostasis in essential hypertension. An increase in intracellular free Ca2+ concentration without an accompanying change in the intracellular Na+ suggests, among many possibilities, that the Ca2+/Mg(2+)-ATPase may be inhibited in the hypertensive renal tissue.     

Utilization of fatty acids in perfused hypothermic dog kidney

Utilization of oleic acid in whole dog kidneys perfused in vitro for 24 hr at 10 degrees C was studied, and the data were correlated with results on the utilization of oleic acid in kidney slices incubated in the same perfusate at 10 degrees C. Kidneys perfused without added oleate lost 35% of their total lipid content and 27% of their phospholipids. Addition of serum albumin-bound oleate to the perfusate prevented the loss of neutral lipid and reduced the loss of phospholipid to 8%. The kidney slices incorporated 29% of the added oleate into lipid and oxidized 3.2% to CO(2). Oleate apparently largely replaces endogenous fatty acids which are oxidized to meet the energy requirements of the kidney. The loss of phospholipid from the perfused organ is taken as an indication of cell damage, which may be reduced but is not prevented by the addition of oleate to the perfusate.     

Effect of drug treatment on liver-slice function following 72-hour hypothermic perfusion

The viability of hypothermically perfused dog liver was evaluated with a tissue-slice technique. After being preserved for 72 hr, slices of liver were incubated at 30 degrees C for as long as 2 hr; then water content, K+/Na+ ratio, and ATP concentration were measured. Dog livers were assigned to the following experimental groups: Group 1 (no preservation; control); Group 2 (livers preserved for 72 hr); Group 3 (donor animals pretreated with 3.5 mg/kg of chlorpromazine (CPZ) and 20 mg/kg of methylprednisolone (MP), and livers preserved for 72 hr); Group 4 (livers pretreated with 2-deoxycoformycin (2-DOC), 50 mg/liter, and preserved for 72 hr); and Group 5 (combination of Group 3 and Group 4 treatments). Livers in Groups 2, 3, and 4 lost K+ during preservation, and the mean K+/Na+ ratio significantly decreased from a control value of 4.2 +/- 0.4 to 1.5-1.9 (P less than 0.05). Group 5 livers did not lose K+; mean K+/Na+ ratio was 3.9 +/- 0.5. Fresh livers (no preservation) rapidly reaccumulated K+ when the tissue slices were incubated for 2 hr at 30 degrees C; mean K+/Na+ ratio was 3.7 +/- 0.5. Tissue slices from Group 2 livers (72 hr preservation), and livers pretreated with CPZ-MP (Group 3) or pretreated with 2-DOC (Group 4) did not significantly reaccumulate K+ at 30 degrees C; mean K+/Na+ ratio was 1.7-2.1. Only slices prepared from liver pretreated with both CPZ-MP and 2-DOC reaccumulated K+; mean K+/Na+ ratio was 4.6 +/- 1.2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of L-glucose on sodium reabsorption in the isolated perfused rat kidney.

In the isolated perfused rat kidney, sodium reabsorption is enhanced in the presence of 5.5 mM D-glucose. However, it is unclear whether this effect is metabolic or whether it is due to a requirement for sodium transport in the process of glucose reabsorption. A third possibility is solvent drag. In an attempt to differentiate between these possibilities, kidneys were perfused with the D-glucose isomer, L-glucose (L-G), a nonmetabolizable hexose. At a perfusate concentration of 5.5 mM L-G, per cent L-G reabsorption was approximately 30. Inhibition of L-G reabsorption by D-glucose suggests carrier-mediated transport. In the presence of 5.5 mM L-G, sodium reabsorption approximated 92% during the course of perfusion. When L-G was omitted from perfusate, sodium reabsorption ultimately declined to 85%. Since significant metabolism of L-G was not observed, the results are compatible with the hypothesis that enhanced sodium reabsorption may be brought about by some still to be defined aspect of glucose transport.     

Increased Ca++ or mg++ concentration reduces relative tight-junction permeability to Na+ in the cortical thick ascending limb of Henle's loop of rabbit kidney

We have tested whether increased Ca++ and Mg++ concentrations have an effect on transepithelial voltage (PDte) and transepithelial resistance (Rte) in isolated perfused cortical thick ascending limbs (cTAL) of rabbit kidney. The divalent cations added at 2.5, 5.0 and 10.0 mmol.l-1 to the lumen or peritubular bath perfusate led to a concentration-dependent increase in Rte. The maximal response in Rte was observed between 5 and 10 mmol.l-1. No significant change in active transepithelial potential difference (PDte) was observed. The increase in Rte still occurred when the transcellular current was reduced by Ba++ (3 mmol.l-1) added to the lumen perfusate. This suggests that the increase in Rte caused by Ca++ and Mg++ is due to a modification of the paracellular shunt pathway. In the absence of active transport, i.e. when furosemide (5.10(-5) mol.l-1) was added to the lumen perfusate. Ca++ and Mg++ reduced the transepithelial diffusion potential generated by a NaCl gradient established across the epithelium, and thus produced a reduction of the relative permeability for Na+ over Cl- (PNa+/PCl-) of the paracellular shunt pathway. This indicates that divalent cations increase Rte by reducing the sodium permeability of the tight junctions. The observed Ca++ and Mg++ induced reduction of the sodium permeability of the paracellular pathway corresponds to a decrease in net Na+ reabsorption by 5-10%. Since it has been demonstrated that peptide hormones such as parathyrin (PTH) modulate divalent cation and NaCl reabsorptions, in a second series of experiments we tested the effects of PTH (2-20 USP.l-1) and dbcAMP (10(-3) mol.l-1) on PDte and Rte of isolated perfused cTAL segments of rabbit nephron. Neither Rte nor PDte were affected by PTH or dbcAMP.     

Dopamine production by the isolated perfused rat kidney

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 +/- 0.1 ng DA X min-1 X g wet weight-1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 +/- 0.06 ng DA X min-1 X g-1 and denervated kidneys excreted 1.0 +/- 0.07 DA X min-1 X g-1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 +/- 0.1 ng DA X min-1 X g-1 (p less than 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng X min-1 X g-1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 +/- 0.13 ng DA X min-1 X g-1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors.(ABSTRACT TRUNCATED AT 250 WORDS)     

87Rb, 23Na and 31P nuclear magnetic resonance spectroscopy of the perfused rat kidney

87Rb, 23Na and 31P nuclear magnetic resonance (NMR) were used to monitor changes in renal cations and energetics during the induction of hypoxia in the isolated perfused rat kidney. The NMR-determined unidirectional Rb+ flux in normoxic kidneys was shown to be a good measure of net intracellular K+ influx in the perfused rat kidney model. The changes in 87Rb, 23Na and 31P spectra following the induction of hypoxia are consistent with hypoxic depletion of intracellular adenosine triphosphate (ATP) and a subsequent decrease in Na-K-ATPase transport activity. The exponential rate constant for 87Rb+ efflux measured during Rb+ uptake in normoxic kidneys (0.12 +/- 0.01 min-1) was not significantly different to the rate constant for 87Rb+ efflux during the induction of hypoxia (0.16 +/- 0.07 min-1). We conclude that there is no direct effect of hypoxia on renal cellular membrane integrity and that renal cell sensitivity to hypoxia is due to an inability to sustain cellular ion gradients following depletion of intracellular ATP.     

Renal preservation by hypothermic perfusion. IV. The use of gelatin polypeptides as the sole colloid

Rabbit kidneys were perfused with a solution of extracellular electrolyte composition, rendered hypertonic with glucose and containing 1.75% Haemaccel (Hoechst) as the sole colloid. Perfusions were carried out at 10 °C for 24 and 48 hr using perfusion pressures of 20 or 40 mm Hg. Function, was tested by autografting with immediate contralateral nephrectomy. All the kidneys perfused at 20 mm Hg for 24 hr showed excellent life-sustaining function and 7 of 10 survived in the 40 mm Hg group; the difference was not statistically significant. However, all the kidneys perfused for 48 hr failed to sustain life, and histological examination revealed extensive breakdown of the microcirculation. The 24 hr results were similar to those previously obtained with an albumin-based perfusate, but the 48-hr results were inferior: However, the obvious advantages of a well-standardised, cheap, and easily stored perfusate are such as to justify further study of gelatin-derived colloids for organ preservation.     

Kinetics of glucose decarboxylation in the substrate-limited isolated perfused kidney.

Rat kidneys were perfused with a cell-free perfusate containing substrate-free albumin, different glucose concentrations (0.20-5.0 mmol/l), and uniformly labeled 14C-glucose. The rate of glucose decarboxylation (Qox), as a function of [glucose]p, displayed saturation kinetics [Vmax = 0.35 mumol/(g.min); Km = 0.87 mmol/l]; saturation occurred at [glucose]p = 1.0-2.0 mmol/l. Although the presence of as low as 0.2 mmol/l of glucose significantly increased fractional sodium reabsorption (%TNa), there was no correlation between [glucose]p or Qox and % TNa. However, free water clearance (CH2O or CH2O/GFR) was directly proportional to [glucose]p and independent of Qox. We conclude that (1) in the absence of other substrates, renal glucose Qox saturates at hypoglycemic levels of glucose and (2) glucose plays an important role in the generation of solute-free water, a role that is unrelated to glucose Qox.     

The influence of renal function on lactate and glucose metabolism.

The relationship of lactate metabolism to renal function was studied in the isolated perfused rat kidney. A new radioisotopic method has been developed that enables the simultaneous measurement of lactate production and consumption in the presence of physiological concentrations of both lactate and glucose. In kidneys from fed rats, when glucose was absent, lactate production was only 12 mumol/h per g dry wt, and in kidneys from starved rats there was no lactate production, indicating that neither the phosphoenolpyruvate/pyruvate substrate cycle nor other analogous cycles for the recycling of lactate carbon are operating in the intact kidney cortex. Lactate production from glucose occurred at a high rate, at the same time as lactate consumption, demonstrating that lactate recycling between renal cortex and medulla can occur in the intact kidney. Lactate production from glucose correlated with glomerular filtration rate (P less than 0.001), urine flow rate (P less than 0.01) and sodium reabsorption (P less than 0.05). There was significant basal lactate production at zero glomerular filtration rate. Lactate consumption was not correlated with any renal function. When Na+ reabsorption was inhibited with the diuretic frusemide, or when filtration was entirely prevented (the 'non'-filtering kidney'), lactate production was decreased by 39% and 50% respectively. Basal lactate production determined in this way was the same as that calculated above by linear regression. Prevention of filtration, but not the addition of frusemide, significantly inhibited lactate consumption. It is concluded that glycolysis is required for medullary Na+ transport, and that some different transport function(s) require lactate oxidation.     

A search for a defect of proximal transport in denervated kidneys of conscious dogs

The influence of renal nerves on proximal Na+ reabsorption was studied in clearance experiments with unilaterally renal-denervated conscious dogs prepared by surgical bladder division. Two types of experiments were made : A. maximal water diuresis, and B. Total blockade of distal NaCl reabsorption with ethacrynic acid and chlorothiazide. In maximal water diuresis CH2O + CNa was used as a measure of fluid delivery to the distal nephron. At similar GFR on both sides, the proximal reabsorption estimated as GFR--(CH2O + CNa) was 38.4 +/- 5.6 ml/min for the intact and 35.9 +/- 4.2 ml/min for the denervated kidney (n = 6, difference NS). After distal tubular blockade, proximal Na+ reabsorption calculated as filtered load minus urinary excretion was 3.84 +/- 0.43 mmol/min for the intact and 3.91 +/- 0.36 mmol/min for the denervated kidney (n = 6, difference NS). The fractional reabsorption of NA+ was 64.9 +/- 1.0% for the intact and 66.9 +/- 1.1% for the denervated kidney (difference NS). In contrast to data from renal denervation studies with anaesthetized animals, the present experiments did not show any difference in proximal reabsorption between the innervated- and denervated kidney. We conclude that in absence of anaesthesia renal efferent nerves have no major effect on NaCl transport in dog proximal tubule.     

Modulating biochemical perturbations during 72-hour machine perfusion of kidneys: role of preservation solution

This study documents renal biochemistry during hypothermic machine perfusion of kidneys. It is intended to demonstrate that a comprehensive evaluation of organ viability during ex-vivo preservation is needed to increase the number of organs available for transplantation and to reduce the current renal discard rate. Porcine kidneys were hypothermically machine perfused for 72 h with either Unisol-UHK or Belzer-Machine Perfusion Solution, (Belzer-MPS). Renal perfusate samples were periodically collected and biochemically analyzed. Significant differences were measured in the renal metabolic activity between the two experimental groups while similar values for traditional parameters such as renal flow rate and vascular resistance values were recorded. The effluent of UHK perfused kidneys showed strong metabolites and NH(4)(+) dynamics (P<0.05 vs. baseline), while the Belzer-MPS kidneys metabolic activity led to little or no change of the effluent biochemistry relative to baseline.     

The effects of oxygen free radicals on the preserved kidney

This study evaluated the effect of specific scavengers of oxygen derived free radicals on the results of kidney preservation. The immediate function of rabbit kidneys preserved for 24 hr by hypothermic perfusion was studied on an ex vivo shunt. A significant improvement in creatinine clearance was seen when the perfusate was treated with superoxide dismutase (SOD) and catalase (CAT), with values of 261 ± 82 ml/hr vs control values of 203 ± 72 ml/hr, P < 0.05. This effect was enhanced if a long-persistent polyethylene glycol-linked form of SOD, namely PEG-SOD, was used (330 ± 58 ml/hr, P < 0.01). Recipient treatment and other modifications designed to protect against free radicals resulted in similar improvement in function. In contrast, no effect of free radical scavengers could be demonstrated in kidneys which were preserved by flush cooling, whether the agents were added to the flushing solution, given to the recipient, or both.     

Renal cortical intermediary metabolism in the recovery phase of postischemic acute renal failure in the dog.

Renal metabolism has been studied in eight dogs before and 48 hr after a 60-min period of renal ischemia induced by clamping the left renal artery with the simultaneous removal of the right kidney, and in 12 sham-operated animals. The study involved the measurement of renal uptake and production of lactate, glutamine, glutamate, alanine, ammonium, and oxygen, and the measurement of the tissue concentrations of ATP, glutamine, lactate, alpha-ketoglutarate, aspartate, and alanine in the renal cortex. Two days after a temporary renal ischemia, the remaining kidney showed a 22% decrease in glomerular filtration rate (GFR) and a 25% decrease in renal plasma flow. Fractional sodium and potassium excretions were similar to those of control dogs. Renal production or extraction of glutamine, glutamate, alanine, ammonium, and oxygen (all expressed by 100 ml of GFR) was not significantly different in basal conditions or 2 days after ischemia, but lactate extraction was reduced in postischemic kidneys (-101 +/- 29 vs -204 +/- 38 mumol/100 ml GFR in control dogs). The cortical concentrations of glutamine and glutamate were lower in postischemic than in control kidneys. No differences were found in cortical concentration of alpha-ketoglutarate, aspartate, lactate, pyruvate, or ATP, but total nucleotides and inorganic phosphate were decreased in postischemic kidneys. It is concluded that in the recovery phase of the ischemia, a decreased lactate uptake is the main metabolic change, and total ATP production is adapted to the decrease of GFR and sodium reabsorption.