Clinical Investigation

Kidney International (1988) 34, 825–831; doi:10.1038/ki.1988.256

Atrial natriuretic peptide and the renal response to hypervolemia in nephrotic humans

Craig Peterson1, Berit Madsen1, Andrew Perlman1, Alex Y M Chan1 and Bryan D Myers1

1Department of Medicine, Division of Nephrology, Stanford University Medical Center, Stanford, California, USA

Correspondence: Bryan D Myers MD, Stanford University Medical Center, Department of Medicine, S-215, Division of Nephrology, Stanford, California 94305, USA.

Received 30 December 1987; Revised 5 August 1988.

Top

Abstract

Atrial natriuretic peptide and the renal response to hypervolemia in nephrotic humans. To elucidate the abnormality of body fluid homeostasis that attends the nephrotic syndrome, we compared the atrial hormonal and renal excretory and vasomotor responses to water immersion of nephrotic patients (N = 10) with those of healthy controls (N = 9). Nephrotics exhibited depressed baseline levels of atrial natriuretic peptide (ANP, P < 0.05) and lower rates of urine flow and sodium excretion (P < 0.01). Although immersion-induced hypervolemia increased plasma ANP to equivalent levels (75 plusminus 19 vs. 60 plusminus 6 pg/ ml), the disparity in corresponding urinary flow (5 plusminus 1 vs. 13 plusminus 2 ml/ min, P < 0.01) and sodium excretion (171 plusminus 42 vs. 540 plusminus 65 microEq/min, P < 0.01) grew larger. In contrast, immersion caused an equivalent reduction of renal vascular resistance by 16 and 17%, respectively (P < 0.01). Despite higher renal plasma flow and lower oncotic pressure of plasma, the glomerular filtration rate remained constant during immersion in both groups. Similar constancy of fractional clearances of dextrans of graded size suggests that immersion may have lowered the glomerular transcapillary hydraulic pressure difference (DeltaP). We conclude that renal vasomotor responsiveness to hypervolemia is preserved in nephrotics, but that the mediatory role of ANP in this response is uncertain. By contrast, diminished responsiveness of the distal nephron to the natriuretic action of endogenous ANP could contribute to edema formation in the nephrotic syndrome.

Top

References

  1. Reineck J: Mechanisms of edema formation in the nephrotic syndrome, in Contemporary Issues in Nephrology, edited by BM Brenner, JH Stein, vol 9, New York, Churchill Livingstone, 1982, pp. 31–46
  2. Bailie MD: Nephrotic edema. Sem Nephrol 3:244–55, 1983
  3. Dorhout-Mees EJ, Geers AB, Koomans HA: Blood volume and sodium retention in the nephrotic syndrome: A controversial patho physiological concept. Nephron 36:201–211, 1984
  4. Chandra M, Hoyer JR, Lew y JE: Renal function in rats with unilateral proteinuria produced by renal perfusion with aminonu-cleoside. Pediatr Res 15:340–344, 1981 | PubMed | ISI | ChemPort |
  5. Ichikawa I, Rennke HG, Hoyer JR, Badr KF, Schor N, Troy JL, Leehene CP, Brenner BM: Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome. J Clin Invest 71:91–103, 1983 | PubMed | ISI | ChemPort |
  6. Perico N, Delaini F, Lupini C, Remuzzi G: Renal response to atrial peptides is reduced in experimental nephrosis. Am J Physiol F654–F660, 1987 | PubMed | ISI | ChemPort |
  7. Koepke JP, DiBona GF: Blunted natriuresis to atrial natriuretic peptide in chronic sodium-retaining disorders. Am J Physiol 252:F865–F871, 1987 | PubMed | ISI | ChemPort |
  8. Bichet DG, Groves BM, Schrier RW: Mechanisms of improve ment of water and sodium excretion by immersion in decompensa ted cirrhotic patients. Kidney Int 24:788–794, 1983 | PubMed | ChemPort |
  9. Epstein M, Loutzenhiser R, Friedland E, Aceto RM, Camargo MJF, Atlas SA: Relationship of increased plasma atrial natriuretic factor and renal sodium handling during immersion induced central hypervolemia in normal humans. J Clin Invest 79:738–745, 1987
  10. Krishna GG, Danovitch GM: Effects of water immersion on renal function in the nephrotic syndrome. Kidney Int 21:393–401, 1982
  11. Epstein M, Levinson R, Loutzenhiser R: Effects of water immersion on renal hemodynamics in normal man. J Appl Physiol 41:230–233, 1976
  12. Epstein M, Larios O, Johnson G: Effects of water immersion on plasma catecholamines in decompensated cirrhosis. Miner Electrol Metab 11:25–34, 1985
  13. Davies DF, Shock NW: Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest 29:496–507, 1950 | PubMed | ISI | ChemPort |
  14. Aurell M: Renal response in man to plasma volume expansion and angiotensin. Scand J Clin Lab Invest 24:3–59, 1969
  15. Shemesh O, Deen WM, Brenner BM, McNeely E, Myers BD: Effect of colloid volume expansion of glomerular barrier size-selectivity in humans. Kidney Int 29:916–923, 1986 | PubMed | ISI | ChemPort |
  16. Brodwall EK: Renal extraction of PAH in renal disease. Scand J Clin Lab Invest 16:12–20, 1960
  17. Bergstrom J, Bucht H, Ek E, Josephson B, Sundell H, Werko L: The renal extraction of para-aminohippurate in normal persons and patients with diseases kidneys. Scand J Clin Lab Invest 11:361–375, 1960
  18. Carghill WH: The measurement of glomerular and tubular plasma flow in the normal and diseased human kidney. J Clin Invest 28:189–192, 1948
  19. Chang RLS, Deen WM, Robertson CR, Bennett CM, Glassock RJ, Brenner BM: Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran. J Clin Invest 57:1272–1280, 1976 | PubMed | ISI | ChemPort |
  20. Chang RL, Ueki IF, Troy JL, Deen WM, Robertson CR, Brenner BM: Permselectivity of the glomerular capillary wall to macromolecules: II. Experimental studies in rats using neutral dextran. Biophys J 15:887–895, 1975 | PubMed | ISI | ChemPort |
  21. Shemesh O, Ross JC, Deen WM, Grant GW, Myers BD: Nature of the glomerular capillary injury in human membranous glomeru lopathy. J Clin Invest 77:868–877, 1986 | PubMed | ISI | ChemPort |
  22. Deen WM, Bridges CR, Brenner BM, Myers BD: Heteroporous model of glomerular size-selectivity. Application to normal and nephrotic humans. Am J Physiol 249:F374–F389, 1985 | PubMed | ISI | ChemPort |
  23. Cody RJ, Atlas SA, Laragh JH, Kubo SH, Covit AB, Ryman KS, Shaknovich A, Pondolfino K, Clark M, Camargo MJF, Scarborough RM, Lewicki JA: Atrial natriuretic factor in normal subjects and heart failure patients. J Clin Invest 78:1362–1374, 1986 | PubMed | ISI | ChemPort |
  24. Raine AEG, Erne P, Burgisser E, Muller FB, Bolli P, Burkart F, Buhler FR: Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med 315:533–537, 1986 | ISI | ChemPort |
  25. Bernard DB, Alexander EA, Couser WG, Levinsky NG: Renal sodium retention during volume expansion in experimental nephrotic syndrome. Kidney Int 14:478–487, 1978 | PubMed | ISI | ChemPort |
  26. Maddox DA, Bennett CM, Deen WM, Glassock RJ, Knutson D, Brenner BM: Control of proximal tubule fluid reabsorption in experimental glomerulonephritis. J Clin Invest 55:1315–1325, 1975 | PubMed | ISI | ChemPort |
  27. Nonoguchi H, Knepper MA, Manganielle VC: Effects of atrial natriuretic factor on cyclic guanosine monophosphate and cyclic adenosine monophosphate accumulation in microdissected neph ron segments from rats. J Clin Invest 79:500–507, 1987 | PubMed | ChemPort |
  28. Ishikawa S, Saito T, Okada K, Kuzuya T, Kangawa K, Matsuo H: Atrial natriuretic factor increases cyclic GMP and inhibits cyclic AMP in rat renal papillary collecting tubule cells in culture. Biochem Biophys Res Com 130:1147–1153, 1985
  29. Ziedel ML, Silva P, Brenner BM, Seifter JL: cGMP mediates effects of atrial peptides on medullary collecting duct cells. Am J Physiol 252:F551–F559, 1987
  30. Sonnenberg H, Cupples WA, DeBold AJ, Veress AT: Intrare-nal localization of the natriuretic effect of cardiac atrial extract. Can J Physiol Pharmacol 60:1149–1152, 1982
  31. Miyamoto M, Larsen TS, Jamison RL: Effect of atrial natriuretic peptide on vasa recta blood flow. (abstract) Kidney Int 31:280, 1987
  32. Healy DP, Fanestil DD: Localization of atrial natriuretic peptide binding sites within the rat kidney. Am J Physiol 250:F573–F578, 1986
  33. Bianchi C, Gutkowska J, Thibault G, Garcia R, Genest J, Cantin M: Distinct localization of atrial natriuretic factor and angiotensin II binding sites in the glomerulus. Am J Physiol 251:F594–F602, 1986 | PubMed | ChemPort |
  34. Huang CL, Lewicki J, Johnson LK, Cogan MG: Renal mech anisms of action of rat atrial natriuretic factor. J Clin Invest 75:769–773, 1985 | PubMed | ISI | ChemPort |
  35. Dunn BR, Ichikawa I, Pfeffer J, Troy JL, Brenner BM: Renal and systemic hemodynamic effects of synthetic atrial natriuretic peptide in the anesthetized rat. Circ Res 59:237–246, 1986
  36. Marin-Grez M, Fleming JT, Steinhausen M: Atrial natriuretic peptide causes pre-glomerular vasodilatation and postglomerular vasoconstriction in rat kidney. Nature 324:473–476, 1986 | Article | PubMed | ChemPort |
  37. Willassen Y, Ofstad J: Renal sodium excretion and the peritu bular physical factors in essential hypertension. Hypertension 2:771–779, 1980
  38. Deen WM, Robertson CR, Brenner BM: A model of glomerular ultrafiltration in the rat. Am J Physiol 223:1178–1183, 1972 | PubMed | ISI | ChemPort |
  39. Yoshioka T, Rennke HG, Salant DJ, Deen WM, Ichikawa I: Hemodynamic alterations modulate the expansion and the glomer ular sieving defect in rat membranous glomerulopathy (MGN). (abstract) Kidney Int 29:390, 1986
  40. Yoshioka T, Mitarai T, Kon V, Deen WM, Rennke HG, Ichikawa I: Role for angiotensin II in an overt functional protein uria. Kidney Int 30:538–545, 1986 | PubMed | ISI | ChemPort |
  41. Chang RLS, Robertson CR, Deen WM, Brenner BM: Permse lectivity of the glomerular capillary wall to macromolecules: I. Theoretical considerations. Biophys J 15:861–886, 1975 | PubMed | ISI | ChemPort |
  42. Deen WM, Myers BD, Brenner BM: The glomerular barrier to macromolecules: Theoretical and experimental considerations, in Contemporary Issues in Nephrology: Nephrotic Syndrome, edited by B Brenner, J Stein, New York, Churchill Livingstone, 1982, pp. 1–29
  43. Cuneo RC, Espinor EA, Nicholls GM, Yandle TG, Joyce SL, Gilchrist NL: Renal, hemodynamic and hormonal responses to ANP infusion in man and effect on Na+ intake. J Clin Endocrinol Metab 63:946–953, 1986 | PubMed | ChemPort |
  44. Weidmann P, Hasler L, Gnadinger MP, Lang RE, Uehlinger DE, Shaw S, Rascher W, Reubi FC: Blood levels and renal effects of atrial natriuretic peptide in normal man. J Clin Invest 77:734–742, 1986 | ISI | ChemPort |
  45. Gilmore JP: Neural control of extracellular volume in the human and nonhuman primate, in Handbook of Physiology, edited by J Shepherd, F Abboud, S Geiger, Baltimore, Waverly Press, Inc. 1986, pp. 885–915

Extra navigation

.
ADVERTISEMENT