Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1995 Feb;95(2):820–831. doi: 10.1172/JCI117732

Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft.

V Alejandro 1, J D Scandling Jr 1, R K Sibley 1, D Dafoe 1, E Alfrey 1, W Deen 1, B D Myers 1
PMCID: PMC295562  PMID: 7860766

Abstract

Postischemic filtration failure in experimental animals results primarily from depression of the transcapillary hydraulic pressure difference (delta P), a quantity that cannot be determined in humans. To circumvent this limitation we determined the GFR and each of its remaining determinants in transplanted kidneys. Findings in 12 allografts that exhibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). Determinations were made intraoperatively in the exposed graft after 1-3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler flow meter (140 +/- 30 vs 315 +/- 49 ml/min) were significantly lower in group 2 than group 1. Morphometric analysis of glomeruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be similar, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1, respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a mathematical model of glomerular ultrafiltration and a sensitivity analysis to calculate the prevailing range for delta P from the foregoing measured quantities. This revealed delta P to vary from only 20-21 mmHg in group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric analysis revealed the diameters of Bowman's space and tubular lumens, as well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a) that delta P depression is the predominant cause of hypofiltration in this form of postischemic injury; and (b) that afferent vasoconstriction rather than tubular obstruction is the proximate cause of the delta P depression.

Full text

PDF
820

Images in this article

821Image
on p.821
826Image
on p.826
828Image
on p.828

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arendshorst W. J., Finn W. F., Gottschalk C. W. Micropuncture study of acute renal failure following temporary renal ischemia in the rat. Kidney Int Suppl. 1976 Oct;6:S100–S105. [PubMed] [Google Scholar]
  2. Battilana C., Zhang H. P., Olshen R. A., Wexler L., Myers B. D. PAH extraction and estimation of plasma flow in diseased human kidneys. Am J Physiol. 1991 Oct;261(4 Pt 2):F726–F733. doi: 10.1152/ajprenal.1991.261.4.F726. [DOI] [PubMed] [Google Scholar]
  3. Bland J. M., Altman D. G. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986 Feb 8;1(8476):307–310. [PubMed] [Google Scholar]
  4. 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]
  5. Burke T. J., Cronin R. E., Duchin K. L., Peterson L. N., Schrier R. W. Ischemia and tubule obstruction during acute renal failure in dogs: mannitol in protection. Am J Physiol. 1980 Apr;238(4):F305–F314. doi: 10.1152/ajprenal.1980.238.4.F305. [DOI] [PubMed] [Google Scholar]
  6. Canaan-Kühl S., Venkatraman E. S., Ernst S. I., Olshen R. A., Myers B. D. Relationships among protein and albumin concentrations and oncotic pressure in nephrotic plasma. Am J Physiol. 1993 Jun;264(6 Pt 2):F1052–F1059. doi: 10.1152/ajprenal.1993.264.6.F1052. [DOI] [PubMed] [Google Scholar]
  7. Chagnac A., Kiberd B. A., Fariñas M. C., Strober S., Sibley R. K., Hoppe R., Myers B. D. Outcome of the acute glomerular injury in proliferative lupus nephritis. J Clin Invest. 1989 Sep;84(3):922–930. doi: 10.1172/JCI114254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. DiBona G. F. Renal innervation and denervation: lessons from renal transplantation reconsidered. Artif Organs. 1987 Dec;11(6):457–462. doi: 10.1111/j.1525-1594.1987.tb02710.x. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Drumond M. C., Deen W. M. Stokes flow through a row of cylinders between parallel walls: model for the glomerular slit diaphragm. J Biomech Eng. 1994 May;116(2):184–189. doi: 10.1115/1.2895718. [DOI] [PubMed] [Google Scholar]
  12. Drumond M. C., Deen W. M. Structural determinants of glomerular hydraulic permeability. Am J Physiol. 1994 Jan;266(1 Pt 2):F1–12. doi: 10.1152/ajprenal.1994.266.1.F1. [DOI] [PubMed] [Google Scholar]
  13. Drumond M. C., Kristal B., Myers B. D., Deen W. M. Structural basis for reduced glomerular filtration capacity in nephrotic humans. J Clin Invest. 1994 Sep;94(3):1187–1195. doi: 10.1172/JCI117435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dunnill M. S., Halley W. Some observations on the quantitative anatomy of the kidney. J Pathol. 1973 Jun;110(2):113–121. doi: 10.1002/path.1711100202. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Guasch A., Sibley R. K., Huie P., Myers B. D. Extent and course of glomerular injury in human membranous glomerulopathy. Am J Physiol. 1992 Dec;263(6 Pt 2):F1034–F1043. doi: 10.1152/ajprenal.1992.263.6.F1034. [DOI] [PubMed] [Google Scholar]
  18. Hefty T., Fraser S., Nelson K., Bennett W., Barry J. Comparison of UW and Euro-Collins solutions in paired cadaveric kidneys. Transplantation. 1992 Feb;53(2):491–492. [PubMed] [Google Scholar]
  19. Holmer S., Rinne B., Eckardt K. U., Le Hir M., Schricker K., Kaissling B., Riegger G., Kurtz A. Role of renal nerves for the expression of renin in adult rat kidney. Am J Physiol. 1994 May;266(5 Pt 2):F738–F745. doi: 10.1152/ajprenal.1994.266.5.F738. [DOI] [PubMed] [Google Scholar]
  20. Jensen E. B., Gundersen H. J., Osterby R. Determination of membrane thickness distribution from orthogonal intercepts. J Microsc. 1979 Jan;115(1):19–33. doi: 10.1111/j.1365-2818.1979.tb00149.x. [DOI] [PubMed] [Google Scholar]
  21. Jones D. B. Ultrastructure of human acute renal failure. Lab Invest. 1982 Mar;46(3):254–264. [PubMed] [Google Scholar]
  22. Kon V., Yoshioka T., Fogo A., Ichikawa I. Glomerular actions of endothelin in vivo. J Clin Invest. 1989 May;83(5):1762–1767. doi: 10.1172/JCI114079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meyer T. W., Rennke H. G. Progressive glomerular injury after limited renal infarction in the rat. Am J Physiol. 1988 Jun;254(6 Pt 2):F856–F862. doi: 10.1152/ajprenal.1988.254.6.F856. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Moore K., Wendon J., Frazer M., Karani J., Williams R., Badr K. Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome. N Engl J Med. 1992 Dec 17;327(25):1774–1778. doi: 10.1056/NEJM199212173272502. [DOI] [PubMed] [Google Scholar]
  26. Moran S. M., Myers B. D. Course of acute renal failure studied by a model of creatinine kinetics. Kidney Int. 1985 Jun;27(6):928–937. doi: 10.1038/ki.1985.101. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Myers B. D., Moran S. M. Hemodynamically mediated acute renal failure. N Engl J Med. 1986 Jan 9;314(2):97–105. doi: 10.1056/NEJM198601093140207. [DOI] [PubMed] [Google Scholar]
  29. Myers B. D., Nelson R. G., Williams G. W., Bennett P. H., Hardy S. A., Berg R. L., Loon N., Knowler W. C., Mitch W. E. Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset. J Clin Invest. 1991 Aug;88(2):524–530. doi: 10.1172/JCI115335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Myers B. D., Newton L., Boshkos C., Macoviak J. A., Frist W. H., Derby G. C., Perlroth M. G., Sibley R. K. Chronic injury of human renal microvessels with low-dose cyclosporine therapy. Transplantation. 1988 Nov;46(5):694–703. doi: 10.1097/00007890-198811000-00014. [DOI] [PubMed] [Google Scholar]
  31. Nyengaard J. R., Bendtsen T. F. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec. 1992 Feb;232(2):194–201. doi: 10.1002/ar.1092320205. [DOI] [PubMed] [Google Scholar]
  32. Olsen S., Burdick J. F., Keown P. A., Wallace A. C., Racusen L. C., Solez K. Primary acute renal failure ("acute tubular necrosis") in the transplanted kidney: morphology and pathogenesis. Medicine (Baltimore) 1989 May;68(3):173–187. doi: 10.1097/00005792-198905000-00005. [DOI] [PubMed] [Google Scholar]
  33. Robinette J. B., Conger J. D. Angiotensin and thromboxane in the enhanced renal adrenergic nerve sensitivity of acute renal failure. J Clin Invest. 1990 Nov;86(5):1532–1539. doi: 10.1172/JCI114872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schnermann J. Regulation of single nephron filtration rate by feedback-facts and theories. Clin Nephrol. 1975;3(3):75–81. [PubMed] [Google Scholar]
  35. Solez K., Morel-Maroger L., Sraer J. D. The morphology of "acute tubular necrosis" in man: analysis of 57 renal biopsies and a comparison with the glycerol model. Medicine (Baltimore) 1979 Sep;58(5):362–376. [PubMed] [Google Scholar]
  36. Solez K., Racusen L. C., Marcussen N., Slatnik I., Keown P., Burdick J. F., Olsen S. Morphology of ischemic acute renal failure, normal function, and cyclosporine toxicity in cyclosporine-treated renal allograft recipients. Kidney Int. 1993 May;43(5):1058–1067. doi: 10.1038/ki.1993.148. [DOI] [PubMed] [Google Scholar]
  37. Stein J. H. The glomerulus in acute renal failure. J Lab Clin Med. 1977 Aug;90(2):227–230. [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. Williams R. H., Thomas C. E., Navar L. G., Evan A. P. Hemodynamic and single nephron function during the maintenance phase of ischemic acute renal failure in the dog. Kidney Int. 1981 Apr;19(4):503–515. doi: 10.1038/ki.1981.48. [DOI] [PubMed] [Google Scholar]
  41. Yagil Y., Myers B. D., Jamison R. L. Course and pathogenesis of postischemic acute renal failure in the rat. Am J Physiol. 1988 Aug;255(2 Pt 2):F257–F264. doi: 10.1152/ajprenal.1988.255.2.F257. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES