Clinical Investigation

Kidney International (1979) 16, 179–186; doi:10.1038/ki.1979.119

Inulin: An inadequate marker of glomerular filtration rate in kidney donors and transplant recipients?

Robert W Rosenbaum1, Keith A Hruska1, Charles Anderson1, Alan M Robson1, Eduardo Slatopolsky1 and Saulo Klahr1

1Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Correspondence: Dr S Klahr, Washington University School of Medicine, Department of Medicine, Renal Division, 4550 Scott Avenue, St. Louis, Missouri 63110, USA

Received 11 April 1978; Revised 22 January 1979.

Top

Abstract

Inulin: An inadequate marker of glomerular filtration rate in kidney donors and transplant recipients? During a systematic evaluation of stable renal transplant recipients, we noted a marked discrepancy between the inulin and creatinine clearance values. The CCr/CIn ratio was 1.02 plusminus 0.02 in "normal" subjects and 1.47 plusminus 0.15 in 20 transplant recipients. The CCr/CIn ratio of 14 living related recipients (1.51 plusminus 0.08) was not significantly different from that of cadaver recipients (1.37 plusminus 0.04). Evaluation of ten paired donors and recipients demonstrated a CCr/CIn ratio of 1.34 plusminus 0.06 and 1.51 plusminus 0.10, respectively (NS). In three donors, the CCr/CIn was 1.04 plusminus 0.02 before nephrectomy and 1.25 plusminus 0.08, 1 week after nephrectomy. The ratio in the recipients was 1.45 plusminus 0.13 1 week after transplantation. Other markers of glomerular filtration, urea and iodothalamate (Io), were evaluated. Curea/CCr ratios were similar in normals, donors, and recipients (0.62, 0.62, 0.55, respectively). The Curea/CIn ratio was 0.63 in normal subjects; it was, however, 0.72 plusminus 0.05 in donors and 0.9 plusminus 0.06 in recipients. CIo/CCr and CIO/CIn ratios in normal subjects were the same at 1.02 plusminus .04. CIO/CCr ratio was 0.95 plusminus 0.04 in recipients and 0.96 plusminus 0.03 in donors. The CIO/CIn ratio was 1.43 plusminus 0.08 in recipients and 1.23 plusminus 0.04 in donors. The data reveal a marked discrepancy between CCr and CIn in renal transplant recipients whether living related or cadaver donors, as well as in living related donors, were used. Furthermore, this discrepancy is manifest by 1 week after transplantation in both donors and recipients. Our data suggest that increased creatinine secretion is not solely responsible for this discrepancy, and that there may be an impairment to filtration of inulin at the level of the glomerulus. Back diffusion of filtered inulin, although unlikely, cannot be ruled out from the present data.

L'inuline: Indicateur de filtration glomérulaire inadéquat chez les donneurs de reins et les sujets transplantés. Au cours d'une étude systématique de malades transplantés, en état stable, il a été observé une discordance importante entre les valeurs des clearances de l'inuline et de la créatinine. Le rapport CCr/CIn est de 1,02 plusminus 0,02 chez les sujets normaux et de 1,47 plusminus 0,15 chez 20 transplantés. Ce rapport n'est pas significativement différent chez 14 transplantés avec des reins de donneurs vivants apparentés (1,51 plusminus 0,08) et des transplantés avec des reins de cadavres (1,37 plusminus 0,04). L'étude de dix paires de donneurs et receveurs a montré un rapport de 1,34 plusminus 0,06 et 1,5 plusminus 0,10, respectivement (NS). Chez trois donneurs le rapport était de 1,04 plusminus 0,02 avant et de 1,25 plusminus 0,08 une semaine après la néphrectomie. Le rapport était de 1,45 plusminus 0,13 chez les receveurs une semaine après la transplantation. D'autres marqueurs de la filtration glomérulaire, l'urée et l'iodothalamate (Io), ont été étudiés. Le rapport Curée/CCr est semblable chez les normaux, les donneurs et les receveurs (0,62, 0,62, et 0,55 repectivement). Le rapport Curée/CIn est de 0,63 chez les sujets normaux, mais de 0,72 plusminus 0,05 chez les donneurs et de 0,9 plusminus 0,06 chez les receveurs. Les rapports CIo/CCr et CIO/CIn sont semblables chez les sujets normaux (1,02 plusminus 0,04). CIO/CCr est de 0,95 plusminus 0,04 chez les receveurs et de 0,96 plusminus 0,03 chez les donneurs. Le rapport CIO/CIn est de 1,43 plusminus 0,08 chez les receveurs et de 1,23 plusminus 0,04 chez les donneurs. Ces résultats révèlent une discordance entre CCr et CIn chez les receveurs, que ce soit de reins de donneurs vivants ou de cadavres, et chez les donneurs apparentés. De plus, cette discordance est évidente une semaine après la transplantation à la fois chez les donneurs et les receveurs. Nos résultats suggèrent qu'une augmentation de la sécrétion de créatinine n'est pas seule responsable de la discordance et qu'il peut y avoir une altération de la filtration de l'inuline dans le glomérule. La rétro-diffusion de l'inuline ne peut pas être éliminée à partir des résultats obtenus, encore qu'elle paraisse peu probable.

Top

References

  1. Richards AN, Bott PA, Westfall BB: Renal excretion of inulin, creatinine, and xylose in normal dogs. Proc Soc Exp Biol 32:73–74, 1934
  2. Shannon JA, Smith HW: The excretion of inulin, xylose, and urea by normal and phlorinized man. J Clin Invest 14:393–401, 1935 | PubMed | ChemPort |
  3. Smith HW: The Kidney: Structure and Function in Health and Disease. New York, Oxford University Press, 1951
  4. Miller BE, Winkler A: The renal excretion of endogenous creatinine in man, comparison with exogenous creatinine and inulin. J Clin invest 17:31–39, 1938
  5. Hare K, Goldstein K, Barnett HL, McNamara H, Hare RS: Renal excretion of creatinine in man (abst). Fed Proc 8:67, 1949
  6. Mattar G, Barnett H, McNamara H, Lauson H: Measurement of glomerular filtration rate in children with kidney disease. J Clin Invest 31:938–945, 1952
  7. Brouhard B, Travis LB, Cunningham RJ III, Berger M, Carvajal H: Simultaneous iothalamate, creatinine and urea clearances in children with renal disease. Pediatrics 59:219–223, 1977
  8. Skov PE: Glomerular filtration rate in patients with severe and very severe renal insufficiency. Acta Med Scand 187:419–428, 1970
  9. Marsh WH, Fingerhut B, Miller H: Automated and manual direct methods for the determination of blood urea. Clin Chem 11:624–627, 1965
  10. Chasson AL, Grady HT, Stanley MA: Determination of creatinine by means of automatic chemical analysis. Am J Clin Pathol 35:83–88, 1961
  11. White RP, Samson FE: Determination of inulin in plasma and urine by use of antrone. J Lab Clin Med 43:475–478, 1954
  12. Arant BS, Edelmann CM, Spitzer AL: The consequence of creatinine and inulin clearances in children. Use of the Technicon Autoanalyzer. J Pediatr 81:559–561, 1972 | PubMed | ISI |
  13. Ikkos D, Strom L: A comparison of the endogenous creatinine clearances in children. Acta Paediatr 44:426–434, 1955
  14. Smith WW, Finkelstein N, Smith HW: Renal excretion of hexitols (sorbitol, mannitol, and dulcitol) and their derivatives (sorbitan, isomannide, and sorbide) and of endogenous creatinine-like chromogen in dog and man. J Biol Chem 135:231–250, 1940
  15. Steinitz K, Turkand H: The determination of the glomerular filtration by the endogenous creatinine clearance. J Clin Invest 19:285–298, 1940
  16. Elwood CM, Sigmann EM: The measurement of glomerular filtration rate and effective renal plasma flow in man by iothalamate I125 and iodopyroret I131. Circulation 36:441–448, 1967
  17. Polar E, Metcoff J: "True" creatinine chromogen determination in serum and urine by semi-automated analysis. Clin Chem 11:763–770, 1965
  18. Elwood CM, Sigmann EM, Treger C: The measurement of glomerular filtration rate with I125 sodium iothalamate (Conray). Br J Radiol 40:581–583, 1967
  19. Sigmann EM, Elwood C, Reagan ME, Morris AM, Catanzaro A: The renal clearance of 131I labeled sodium iothalamate in man. Invest Urol 2:432–438, 1960
  20. Sigmann EM, Elwood C, Knox F: Measurement of glomerular filtration rate in man with sodium iothalamate 131I (Conray). J Nucl Med 7:60–68, 1966
  21. Lasser EC, Lang JH, Hamblin AE, Rosen L: Contrast and electrolyte dynamics of the intravenous pyelogram: II. Disparities in serum and urine concentrations of meglumine and anion. Invest Radiol 10:307–313, 1975
  22. Smith HW, Chasis H: The excretional urea in normal man and in subjects with glomerulonephritis. J Clin Invest 17:347–358, 1938 | ChemPort |
  23. Diethelm AG, Aldrite JS, Sterling WA, Morgan JM: Large volume diuresis as a mechanism for immediate maximum renal function after transplantation. Surg Gynecol Obstet 138:869–874, 1974
  24. Skov PE, Hansen HE: Glomerular filtration rate, renal plasma flow and filtration fraction in living related donors before and after nephrectomy. Acta Med Scand 195:97–103, 1974
  25. Robson AM, Giangiacomo J, Kienstra RA, Naqui ST, Ingelfinger JR: Normal glomerular permeability and its modification by minimal change nephrotic syndrome. J Clin Invest 54:1190–1199, 1974
  26. Hulme B, Hardwicke J: Human glomerular permeability to macro molecules in health and disease. Clin Sci 34:515–529, 1968
  27. Beattie J, Corcoran AC: Renal clearances of gross polysaccharide: Observation on glomerular porosity and on the relation of this function to proteinuria in renal disease. J Clin Invest 31:445–450, 1952
  28. Brandt JL, Frank R, Lichtman HC: Normal haemoglobin clearances in chronic proteinuria. Proc Soc Exp Biol 74:863–865, 1950
  29. Buerkert J, Mor J, Murray BN, Robson AM: Glomerular permeability in disease: A proposed role of the glomerular epithelial cell. Proc Am Soc Nephrol, 1976, p. 69
  30. Maddox DA, Bennett CM, Deen WM, Glassock RJ, Knutson D, Daugharty TM, Brenner B: Determinants of glomerular filtration in experimental glomerulonephritis in the rat. J Clin Invest 55:305–318, 1975 | PubMed |
  31. Chang RLS, Robertson CR, Deen WM, Brenner BM: Permselectivity of the glomerular capillary wall to macromolecules: I. Theoretical considerations. Biophys J 15:861–886, 1975 | PubMed | ISI | ChemPort |
  32. Chang RLS, Veki IF, Troy JL, Deen WM, Robertson CR, Brenner BM: Permselectivity of the glomerular capillary wall to macromolecules: II. Experimental studies in rats using neutral dextrans. Biophys J 15:887–906, 1975 | PubMed | ISI | ChemPort |
  33. Ginn HE jr, Unger A, Hund D, Schilling J: Human renal transplantation: An investigation of the functional status of the denervated kidney after successful homotransplantation in identical twins. J Lab Clin Med 56:1–13, 1960
  34. Bricker NS, Guild WR, Reardon JB, Merrill JP: Studies on the functional capacity of a denervated homotransplanted kidney in an identical twin with parallel observations in the donor. J Clin Invest 35:1365–1380, 1956
  35. Ogden D: Donor and recipient function 2 to 4 years after renal homotransplantation. Ann Intern Med 67:998–1006, 1967
  36. Slack TK, Wilson DM: Normal renal function CIn and CPAH in healthy donors before and after nephrectomy. Mayo Clin Proc 51:296–300, 1976 | PubMed | ISI | ChemPort |
  37. Krohn AG, Ogden DA, Holmes JH: Renal function in 29 healthy adults before and after nephrectomy. JAMA 196:110–112, 1966
  38. Pabico R, McKenna B, Freeman RB: Renal function before and after unilateral nephrectomy in renal donors. Kidney Int 8:166–175, 1975 | PubMed | ISI | ChemPort |
  39. Flannigan WJ, Bruns RO, Tabacs FJ, Merrill JP: Serial studies of glomerular filtration rate and renal plasma flow in kidney transplant donors, identical twins and allograft recipients. Am J Surg 116:788–794, 1968

Extra navigation

.
ADVERTISEMENT