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. 1985 Oct;76(4):1440–1448. doi: 10.1172/JCI112122

Pathophysiology of protracted acute renal failure in man.

S M Moran, B D Myers
PMCID: PMC424096  PMID: 2414321

Abstract

Postischemic acute renal failure (ARF) induced by cardiac surgery is commonly prolonged and may be irreversible. To examine whether persistence of postischemic, tubular cell injury accounts for delayed recovery from ARF, we studied 10 patients developing protracted (36 +/- 4 d) ARF after cardiac surgery. The differential clearance and excretion dynamics of probe solutes of graded size were determined. Inulin clearance was depressed (5.0 +/- 1.7 ml/min), while the fractional urinary clearance of dextrans (radii 17-30 A) were elevated above unity. Employing a model of conservation of mass, we calculated that 44% of filtered inulin was lost via transtubular backleak. The clearance and fractional backleak of technetium-labeled DTPA ([99mTc]DTPA, radius = 4 A) were identical to those of inulin (radius 15 A). The time at which inulin or DTPA excretion reached a maximum after an intravenous bolus injection was markedly delayed when compared with control subjects with ARF of brief duration, 102 vs. 11 min. Applying a three-compartment model of inulin/DTPA kinetics (which takes backleak into account) revealed the residence time of intravenously administered inulin/DTPA in the compartment occupied by tubular fluid and urine to be markedly prolonged, 20 vs. 6 min in controls, suggesting reduced velocity of tubular fluid flow. We conclude that protracted human ARF is characterized by transtubular backleak of glomerular ultrafiltrate, such that inulin clearance underestimates true glomerular filtration rate by approximately 50%, and by sluggish tubular fluid flow, which strongly suggests the existence of severe and generalized intraluminal tubular obstruction. Because all patients also exhibited extreme hyperreninemia (16 +/- 2 ng/ml per h) that was inversely related to inulin clearance (r value = -0.83) and urine flow (r value = -0.70), we propose that persistent, angiotensin II-mediated renal vasoconstriction may have delayed healing of the injured tubular epithelium.

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Selected References

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  1. Anderson R. J., Linas S. L., Berns A. S., Henrich W. L., Miller T. R., Gabow P. A., Schrier R. W. Nonoliguric acute renal failure. N Engl J Med. 1977 May 19;296(20):1134–1138. doi: 10.1056/NEJM197705192962002. [DOI] [PubMed] [Google Scholar]
  2. BOJESEN E. The transport of urine in the upper urinary tract. Acta Physiol Scand. 1954 Oct 20;32(1):39–62. doi: 10.1111/j.1748-1716.1954.tb01154.x. [DOI] [PubMed] [Google Scholar]
  3. Brown J. J., Gleadle R. I., Lawson D. H., Lever A. F., Linton A. L., Macadam R. F., Prentice E., Tree M., Robertson J. I. Renin and acute renal failure: studies in man. Br Med J. 1970 Jan 31;1(5691):253–258. doi: 10.1136/bmj.1.5691.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bryer-Ash M., Ammon R. A., Luetscher J. A. Increased inactive renin in diabetes mellitus without evidence of nephropathy. J Clin Endocrinol Metab. 1983 Mar;56(3):557–561. doi: 10.1210/jcem-56-3-557. [DOI] [PubMed] [Google Scholar]
  5. Chang R. S., Robertson C. R., Deen W. M., Brenner B. M. Permselectivity of the glomerular capillary wall to macromolecules. I. Theoretical considerations. Biophys J. 1975 Sep;15(9):861–886. doi: 10.1016/S0006-3495(75)85862-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chervu L. R., Blaufox M. D. Renal radiopharmaceuticals--an update. Semin Nucl Med. 1982 Jul;12(3):224–245. doi: 10.1016/s0001-2998(82)80038-x. [DOI] [PubMed] [Google Scholar]
  7. Deen W. M., Robertson C. R., Brenner B. M. A model of glomerular ultrafiltration in the rat. Am J Physiol. 1972 Nov;223(5):1178–1183. doi: 10.1152/ajplegacy.1972.223.5.1178. [DOI] [PubMed] [Google Scholar]
  8. Donohoe J. F., Venkatachalam M. A., Bernard D. B., Levinsky N. G. Tubular leakage and obstruction after renal ischemia: structural-functional correlations. Kidney Int. 1978 Mar;13(3):208–222. doi: 10.1038/ki.1978.31. [DOI] [PubMed] [Google Scholar]
  9. Eisenbach G. M., Steinhausen M. Micropuncture studies after temporary ischemia of rat kidneys. Pflugers Arch. 1973;343(1):11–25. doi: 10.1007/BF00586571. [DOI] [PubMed] [Google Scholar]
  10. Finn W. F., Chevalier R. L. Recovery from postischemic acute renal failure in the rat. Kidney Int. 1979 Aug;16(2):113–123. doi: 10.1038/ki.1979.112. [DOI] [PubMed] [Google Scholar]
  11. Hilberman M., Myers B. D., Carrie B. J., Derby G., Jamison R. L., Stinson E. B. Acute renal failure following cardiac surgery. J Thorac Cardiovasc Surg. 1979 Jun;77(6):880–888. [PubMed] [Google Scholar]
  12. Hostetter T. H., Rennke H. G., Brenner B. M. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982 Mar;72(3):375–380. doi: 10.1016/0002-9343(82)90490-9. [DOI] [PubMed] [Google Scholar]
  13. Johnston P. A., Bernard D. B., Donohoe J. F., Perrin N. S., Levinsky N. G. Effect of volume expansion on hemodynamics of the hypoperfused rat kidney. J Clin Invest. 1979 Aug;64(2):550–558. doi: 10.1172/JCI109493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller T. R., Anderson R. J., Linas S. L., Henrich W. L., Berns A. S., Gabow P. A., Schrier R. W. Urinary diagnostic indices in acute renal failure: a prospective study. Ann Intern Med. 1978 Jul;89(1):47–50. doi: 10.7326/0003-4819-89-1-47. [DOI] [PubMed] [Google Scholar]
  15. Myers B. D., Carrie B. J., Yee R. R., Hilberman M., Michaels A. S. Pathophysiology of hemodynamically mediated acute renal failure in man. Kidney Int. 1980 Oct;18(4):495–504. doi: 10.1038/ki.1980.163. [DOI] [PubMed] [Google Scholar]
  16. Myers B. D., Chui F., Hilberman M., Michaels A. S. Transtubular leakage of glomerular filtrate in human acute renal failure. Am J Physiol. 1979 Oct;237(4):F319–F325. doi: 10.1152/ajprenal.1979.237.4.F319. [DOI] [PubMed] [Google Scholar]
  17. Myers B. D., Hilberman M., Spencer R. J., Jamison R. L. Glomerular and tubular function in non-oliguric acute renal failure. Am J Med. 1982 Apr;72(4):642–649. doi: 10.1016/0002-9343(82)90475-2. [DOI] [PubMed] [Google Scholar]
  18. Myers B. D., Miller D. C., Mehigan J. T., Olcott C. O., 4th, Golbetz H., Robertson C. R., Derby G., Spencer R., Friedman S. Nature of the renal injury following total renal ischemia in man. J Clin Invest. 1984 Feb;73(2):329–341. doi: 10.1172/JCI111217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Oken D. E. Hemodynamic basis for human acute renal failure (vasomotor nephropathy). Am J Med. 1984 Apr;76(4):702–710. doi: 10.1016/0002-9343(84)90299-7. [DOI] [PubMed] [Google Scholar]
  20. SWANN R. C., MERRILL J. P. The clinical course of acute renal failure. Medicine (Baltimore) 1953 May;32(2):215–292. doi: 10.1097/00005792-195305000-00002. [DOI] [PubMed] [Google Scholar]
  21. TU W. H. PLASMA RENIN ACTIVITY IN ACUTE TUBULAR NECROSIS AND OTHER RENAL DISEASES ASSOCIATED WITH HYPERTENSION. Circulation. 1965 May;31:686–695. doi: 10.1161/01.cir.31.5.686. [DOI] [PubMed] [Google Scholar]
  22. Tanner G. A., Sloan K. L., Sophasan S. Effects of renal artery occlusion on kidney function in the rat. Kidney Int. 1973 Dec;4(6):377–389. doi: 10.1038/ki.1973.134. [DOI] [PubMed] [Google Scholar]
  23. Tanner G. A., Sophasan S. Kidney pressures after temporary renal artery occlusion in the rat. Am J Physiol. 1976 Apr;230(4):1173–1181. doi: 10.1152/ajplegacy.1976.230.4.1173. [DOI] [PubMed] [Google Scholar]

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