RENAL FUNCTION DURING PROLONGED EXERCISE Jan Castenfors Karolinska Instituter Stockholm, Sweden

Introduction For a long time it has been known that intensive exercise influences renal function. In 1878 Leube reported proteinuria following strenous exercise among soldiers whose early morning urine was free of protein. In 1910 Barach studied the urine of marathon runners and found protein, hyaline and granular casts, and also red blood cells. Over the past few years the mechanism and significance of the renal involvement during exercise has been extensively studied.:'-O The purpose of the present report is to give a comprehensive survey of renal function during exercise with emphasis on prolonged heavy exercise. In order to elucidate the effect of such exercise on renal function, this work has been subdivided into renal hemodynamics, concentration mechanisms, electrolyte excretion, and proteinuria. For data we used our results from an investigation of renal function in normal subjects during an 85-km ski race.?, Renal hemodynamic changes, however, could be studied only during short periods of heavy exercise under laboratory conditions, and therefore in this case data from our results in healthy volunteers are also presented.!', l o Renal Hemodynamics During rest in the supine position, renal blood flow is about 1.2 1/min or 20% of the cardiac output. Renal plasma flow (RPF) is 700 ml/min, about 15% of which is filtered through the glomeruli-the glomerular filtration rate (GFR). During exercise, the need for increased blood flow through the exercising muscles necessitates a decrease in blood flow in the splanchnic and renal circulations. This decrease in RPF and renal blood flow (RBF) is proportional 1 ) . Nevertheless, renal autoregulation tries to the severity of exercise (FIGURE to preserve GFR, which is less markedly decreased. Thus, with increasing renal vasoconstriction, a greater part of the diminishing RPF is filtered. This relative increase in filtration is usually expressed as an increased filtration fraction ( F F ) , which is increased from 15% to about 25% during short heavy exercise under laboratory conditions (FIGURE 2). During prolonged heavy exercise it has been impossible to study RBF in man, and only semiquantitative evaluations of G F R (by endogenous creatinine clearance) are available. During an 85-km ski race there was a mean decrease 3), which agrees with other in creatinine clearance of about 30% (FIGURE reports on prolonged exercise.G Urine flow also showed a decrease of about 30%, and there was a significant correlation between the decrease in urine flow and the creatinine clearance, suggesting that the decrease in urine flow was mainly due to a decrease in GFR. Even during short heavy exercise, inulin

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FIGURE 2. Effect of supine exercise in normal subjects on renal hemodynamics. Mean values of PAH extraction (El-AEl), Cl*.4~~, C, FF, and heart rate are shown. x denotes a statistically significant difference compared with period 2. (From Castenfors." By permission of Acfa Physiologicu Scatidinavica.)

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FIGURE 3. Urine flow and the glomerular filtration rate. Effect of prolonged heavy exercise on urine flow and endogenous creatinine clearance. Mean values 2 standard deviations (SD). (After Castenfors et d.‘)

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clearance (which is a more reliable measure of GFR than creatinine clearance) was not decreased more than about 30%.3 If it is assumed that the FF was 25%, then there was approximately a 50% decrease of RPF and RBF during the ski race.

Urinary Water Excretion Water excretion in the urine is mainly regulated by antidiuretic hormone (ADH), which is influenced by osmoreceptors in the brain and also by a volume-sensitive mechanism. During exercise, both an increase in osmolarity and a decrease in plasma volume are stimuli for the release of ADH. During short heavy exercise in well-hydrated subjects lo with an “unphysiologically” high urine flow (10-20 ml/min), a decrease in free water clearance (CHz0) has been demonstrated, suggesting an ADH effect. The decrease in urine flow was mainly related to the decrease in CH,O. During prolonged heavy exercise, however, with a more physiological urine flow rate (less than 1 ml/min), no significant changes in CHl0or urine/plasma creatinine ratio were found (FIGURE 4).’ The latter is a sensitive indicator of water conservation during low urine flow rates. I n some studies, a decline in urinary concentrating ability during heavy exercise has been r e p ~ r t e d . ~ .l1 This paradoxical absence of water retention in spite of a probable increased ADH release is difficult to explain. It may be related to a relatively smaller amount of free water available in relation to the changes in osmolar clearance during severe exercise.

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Urinary Electrolyte Excretion Physical exercise induces a significant decrease in the urinary excretion of several electrolytes, especially sodium, whereas potassium excretion increase^.^' A decrease in urinary sodium excretion during heavy exercise of short duration occurs within 15 min.1° This is mainly related to an increase in tubular reabsorption, as the tubular rejection fraction is significantly decreased. In this situation the rather slowly acting aldosterone mechanism cannot be responsible for the sodium retention, which probably is related to poorly understood renal hemodynamic mechanisms. During prolonged heavy exercise (the ski race), there was a similar decrease in the tubular rejection fraction (FIGURE 5 ) . This increased tubular reabsorption of sodium is, however, probably due in part to an increased aldosterone secretion, as an increased plasma renin activity was demonstrated at the end of exercise.” During a ski race of similar duration, an increase in both plasma renin activity and plasma aldosterone concentration has been shown.’? The increased potassium excretion may be partly due to increased aldosterone secretion, but is probably in addition influenced by other factors such as H+excretion and hematuria. Exercise Proteinuria Proteinuria is almost invariably found during heavy and prolonged exercise. There is also an increased incidence of granular and hyaline casts and also blood cells in the urine after heavy exercise, and the name “athletic pseudonephritis” has been proposed for this phen0men0n.l~

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FIGURE4. Urinary water excretion. Effect of prolonged exercise on free water clearance (C,,,,) and urinelplasma creatinine ratio (U/P creat.). Mean values SD are given. (After Castenfors et a/.’)

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In contact sports s x h as boxing or football, renal trauma has been suggested as a cause for these urinary findings. Regardless of the type of sport activity (contact o r noncontact) similar findings in the urine have been reported.“ Football players demonstrate the highest incidence of hematuria, which may indeed be related to renal trauma. Long distance runners, on the other hand, show the highest incidence of protein in the urine, suggesting that the proteinuria is related to other renal mechanisms. The cause of the increased urinary protein excretion is not definitely known; it may be due to increased glomerular permeability, decreased tubular reabsorption, or a combination of both mechanisms. During prolonged heavy exercise (the ski race) there was a statistically significant increase in total protein and albumin excretion (FIGURE 6). In most subjects electrophoresis showed a predominance of albumin, and this was confirmed with a gel filtration technique.

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FIGURE5. Urinary sodium excretion. Effect of prolonged heavy exercise. on urinary sodium excretion and the tubular rejection fraction. Mean values 2 SD are given. Stars denote statistically significant differences between the periods. (After Castenfors er a/.‘)

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The excretion of the low-molecular-weight protein ribonuclease was not changed during exercise. This protein can be expected to be relatively easily filtered by glomeruli and therefore more dependent on tubular reabsorption for its conservation. This suggests that tubular factors are of minor importance as a cause of exercise proteinuria. Albumin has a molecular weight of 69,000, which is just above the “limiting pore radius” of the glomerular mernbrane.l5 An increased glomerular permeability would therefore favor the predominant increase of albumin, which is usually demonstrated in urine during exercise. Several factors probably contribute to the increased glomerular permeability. Increased body temperature during exercise may be a factor, as fever produces albuminuria.16 Another probably important factor is the renal vasoconstriction during exercise, which is characterized by an increased filtration fraction. This

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suggests a relatively more marked constriction of the efferent glomerular arterioli, resulting in an increased filtration pressure and stasis in the glomerular 7). This favors an increased filtration of protein through capillaries (FIGURE the glomerular membrane, to some extent possibly as a result of a stretch pore phenomenon. This phenomenon may also explain the increased incidence of hyaline casts and erythocytes in the urine. The urinary protein excretion is probably proportional to the severity of exercise in the individual subject, but

RENAL VASOCONSTRICTION DURING EXERCISE

INCREASED FILTRATION PRESSURE SLUGGISH BLOOD FLOW STASIS

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FIGURE 7. Effect of exercise on the gtomerular circulation-Hypothetical scheme.

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in a group of normal subjects the most important factors determining the amount of protein excreted are probably minor biological differences (genetic or acquired) in the “limiting pore radius” of the glomerular membrane.’ Indeed, exercise has been used to demonstrate minor subclinical changes in glomerular permability in diabetic patients.17 Hemoglobinuria and Myoglobinuria

March hemoglobinuria and exercise myoglobinuria are rare,lRand the pathogenesis of these conditions is not completely elucidated. March hemoglobinuria usually appears in the urine 1-3 hr after exercise performed in the upright position, and some resultslD indicate that running on a hard surface is of importance in producing this syndrome, suggesting that mechanical trauma to the erythrocyte as it passes through the foot may be a pathogenetic factor. Exercise myoglobinuria, which appears in the urine 24-48 hr after exercise, has been attributed to a break down of muscle fibers from excessive exercise resulting in an increased myoglobin plasma concentration.18 Myoglobin (MW 17,000) is relatively easily filtered by the glomeruli, and the increased excretion in the urine is not a sign of renal impairment. Duration and Magnitude of the Renal Changes

After short heavy exercise, most renal parameters including proteinuria were normalized within 1 hr after the end of the exercise. After prolonged heavy exercise (the 85-km ski race) renal function parameters were normalized within about 10 hr. The small magnitude of exercise proteinuria is illustrated by the fact that in only 3 of the 15 subjects the proteinuria after prolonged severe exercise reached a level that could be detected by usual clinical tests (Albustix) . General Conclusions

During severe exercise, renal blood flow decreases to allow maximal redistribution of cardiac output to the exercising muscles. The glomerular filtration rate is relatively well maintained, resulting in an increased filtration fraction, an important mechanism in producing exercise proteinuria. Urinary water excretion is relatively little influenced during prolonged exercise. Urinary sodium excretion, however, decreases partly due to increased aldosterone secretion. The renal changes are of a transient nature and disappear rapidly after exercise. There is no indication of renal parenchymal damage during heavy prolonged exercise; almost all changes can be attributed to renal vasoconstriction during exercise. References 1. LUEBE,W. 1878. Ober auscheidung von eisweiss im ham des gesunden Menschen. Wirchows Arch. 72: 145-157. 2. BARACH,I. H. 1910. Physiological and pathological effects of severe exercise

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(the Marathon race) on the circulatory and renal system. Arch. Intern. Med. 5: 3 8 2 4 0 5 . 3. CASTENFORS, J. 1967. Renal function during exercise. With special reference to exercise proteinuria and the release of renin. Acta Physiol. Scand. 70 (Suppl. 293) : 1 4 4 . 4. RAUCH,P. J. & I. D. WILSON. 1968. I n Exercise Physiology. H. B. Falls, Ed. : 130-139. Academic Press. New York. N.Y. 5. KACHADORIAN, W. A. & R. E. JOHNSON. 1970. Renal responses to various rates of exercise. J. Appl. Physiol. 28(6): 748-752. 6. REFSUM,H,. E. & S. B. STROMME.1975. Relationship between urine flow, glo-

merular filtration and urine solute concentration during prolonged heavy exercise. Scand. J. Clin. Lab. Invest. 35: 775-780. 7. CASTENFORS, J., F. MOSSFELDT & M. PISCATOR.1967. Effect of prolonged heavy exercise on renal function and urinary protein excretion. Acta Physiol. Scand. 70: 194-206. 8. Bozovic, L., J. CASTENFORS & M. PISCATOR.1967. Effect of prolonged heavy

exercise on urinary protein excretion and plasma renin activity. Acta Physiol. Scand. 7 0 143-146. J. & M. PISCATOR.1967. Renal hemodynamics, urine flow and 9. CASTENFORS, urinary protein excretion during exercise in supine position at different loads. Acta Med. Scand. Suppl. 472: 231-244. 10. CASTENFORS, J. 1967. Renal clearances and urinary sodium and potassium excretion during supine exercise in normal subjects. Acta Physiol. Scand. 7 0 207-214. 1959. Studies of the renal concen11. RAM, L. G., W. Y. W. Au & R. L. SCHEER. tration mechanism. 111. Effect of heavy exercise. J. Clin. Invest. 39: 8-13. 1975. Plasma aldosteron J. A., S. B. STROMME& A. AAKVAAG. 12. SUNDFJORD, (PA), plasma renin activity (PRA) and cortison (PF) during exercise. I n 13. 14. 15. 16. 17. 18. 19.

Metabolic Adaptation to Prolonged Physical Exercise. E. H. Howald, J. R. Poortman & R. Birkhauser, Eds. : 308-314. Verlag. Basel. GARDNER, K. D. 1956. Athletic pseudonephritis-Alteration of urinary sediment by athletic competition. J. Amer. Med. Assoc. 161: 1613-1617. ALYEA,E. P., M. H. PARISH& N. C. DURHAM.1958. Renal response to exercise -Urinary findings. J. Amer. Med. Assoc. 167: 807-813. ARTURSSON, G. & G. WALLENIUS.1964. The clearance of dextran of different molecular sizes in normal humans. Scand. J. Clin. Lab. Invest. 1: 81-86. SCHULTZE, H. E. & J. F. HEREMANS.1966. The urinary proteins. I n Molecular Biology of Human Proteins : 670-731. Elsevier Publishing Co. New York, N.Y. C. E. & E. VIITINGHUS. 1975. Urinary albumin excretion during MOGENSEN, exercise in juvenile diabetes. A provocation test for early abnormalities. Scand. J. Clin. Lab. Invest. 35: 295-300. STAHL,C. W. 1957. March hemoglobinuria. Report of five cases in students at Ohio State University. J. Amer. Med. Assoc. 164: 1458-1460. BUCKLE,R. M. 1965. Exertional (march) hemoglobinurea. Reduction of hemolytic episodes by use of Sorbo-Rubber insoles in shoes. Lancet i: 1136-1138.

Renal function during prolonged exercise.

RENAL FUNCTION DURING PROLONGED EXERCISE Jan Castenfors Karolinska Instituter Stockholm, Sweden Introduction For a long time it has been known that i...
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