Journal of Renal Nutrition
Volume 12, Issue 3 , Pages 151-159 , July 2002

The role of growth factors and ammonia in the genesis of hypokalemic nephropathy

  • Fernando C. Fervenza, MD, PhD

      Affiliations

    • Research Service Veterans Affairs, Palo Alto Health Care System, and the Division of Nephrology, Department Medicine, Stanford University, Palo Alto, CA.
  • ,
  • Ralph Rabkin, MD

      Affiliations

    • Division of Nephrology, Mayo Clinic, Rochester, MN.

References 

  1. Weiner ID, Wingo C. Hypokalemia, consequences, causes, and correction. J Am Soc Nephrol. 1997;8:1179–1188
  2. Abdel-Rahman EM, Moorthy AV. End-stage renal disease (ESRD) in patients with eating disorders. Clin Nephrol. 1997;47:106–111
  3. Schwartz WB, Relman AS. Effects of electrolyte disordes on renal structure and function. N Engl J Med. 1967;276:383–389
  4. Relman AS, Schwartz WB. The kidney in potassium depletion. Am J Med. 1958;24:764–773
  5. Morrison AB, Gardner KD. The effect of potassium-deficiency on the reabsorption of protein in the renal tubule of the rat. J Exp Med. 1963;118:479–487
  6. Walter SJ, Shore AC, Shirley DG. Effects of potassium depletion on renal tubular function in the rat. Clin Sci. 1988;75:621–628
  7. Mujais SK, Katz AI. Potassium deficiency. In: 2nd ed.  Seldin DW,  Giebisch G editor. The Kidney: Physiology and Pathophysiology. New York, NY: Raven; 1991;p. 2249–2278
  8. Marples D, Frokiaer J, Dorup J, et al.  Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex. J Clin Invest. 1996;97:1960–1968
  9. Berl TS, Linas L, Aisenbery GA. On the mechanism of polyuria in potassium depletion. J Clin Invest. 1977;60:620–625
  10. Linas S, Dickmann D. Mechanism of the decreased renal blood flow in the potassium-depleted conscious rat. Kidney Int. 1982;21:757–764
  11. Ray PE, McCune BK, Gomez RA, et al.  Renal vascular induction of TGF-β2 and renin by potassium depletion. Kidney Int. 1993;44:1006–1013
  12. Barri YM, Wingo CS. The effects of potassium depletion and supplementation on blood pressure: A clinical review. Am J Med Sci. 1997;314:37–40
  13. Cappucio FP, MacGregor GA. Does potassium supplementation lower blood pressure? A meta-analysis of published data. J Hypertens. 1991;9:465–473
  14. Svetkey LP, Yarger WE, Feussner JR, et al.  Double-blind placebo-controlled trial of potassium chloride in the treatment of mild hypertension. Hypertension. 1987;9:444–450
  15. Ray PE, Suga S-I, Liu X-H, et al.  Chronic potassium depletion induces renal injury, salt sensitivity, and hypertension in young rats. Kidney Int. 2001;59:1850–1858
  16. Paller MA, Douglas JG, Linas SL. Mechanism of decreased vascular reactivity to angiotensin II in conscious, potassium-deficient rats. J Clin Invest. 1984;73:79–86
  17. Simonopoulos A. Growth characteristis in patients with Bartter's syndrome. Nephron. 1979;23:130–135
  18. Dorup I. Magnesium and potassium deficiency. Its diagnosis, occurrence and treatment in diuretic therapy and its consequences for growth, protein synthesis and growth factors. Acta Physiol Scand Suppl. 1994;150:1–55
  19. Hsu FW, Tsao T, Rabkin R. IGF-I axis in kidney and skeletal muscle of K deficient rats. Kidney Int. 1997;52:363–370
  20. Elger M, Bankir L, Kriz W. Morphometric analysis of kidney hypertrophy in rats after chronic potassium depletion. Am J Physiol. 1992;262:F656–F667
  21. Tobak GF. Phosphatidylcholine metabolism during renal growth and regeneration. Am J Physiol. 1984;246:F249–F259
  22. Fourman PR, McCane A, Parker RA. Chronic disease in rats following a temporary deficiency of potassium. Br J Exp Pathol. 1956;37:40–44
  23. Cremer W, Bock KD. Symptoms and course of chronic hypokalemic nephropathy in man. Clin Nephrol. 1976;7:112–119
  24. Tolins JP, Hostetter MK, Hostetter TH. Hypokalemic nephropathy in the rat. J Clin Invest. 1987;79:1447–1458
  25. Torres VE, Young WF, Offord KP, et al.  Association of hypokalemia, aldosteronism, and renal cysts. N Engl J Med. 1990;322:345–351
  26. Azzi M, Battaglia C, Chatellier C, et al.  Hypokalemia, aldosteronism, and renal cysts. N Engl J Med. 1990;323:130; (letter)
  27. Ogasawara M, Nomura K, Toraya S, et al.  Clinical implications of renal cyst in primary aldosteronism. Endocrine J. 1996;43:261–268
  28. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: Biological actions. Endocrine Rev. 1995;16:3–34
  29. Shimasaki S, Ling N. Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6). Prog Growth Factor Res. 1991;3:243–266
  30. Thissen J-P, Ketelslegers J-M, Underwood LE. Nutritional regulation of the insulin-like growth factors. Endocrine Rev. 1994;15:80–101
  31. Flyvbjerg A, Thorlacius-Ussing O, Naeraa R, et al.  Kidney tissue somatomedin C and initial growth in diabetic and uninephrectomized rats. Diabetologia. 1988;31:310–314
  32. Flyvbjerg A, Marshall SM, Frystyk J, et al.  Insulin-like growth factor I in initial renal hypertrophy in potassium-depleted rats. Am J Physiol. 1992;262:F1023–F1031
  33. Rohan RM, Unterman TG, Liu L, et al.  Expression of the insulin-like growth factor system in the hypokalemic rat kidney. Am J Physiol. 1997;272:F661–F667
  34. Sharma K, Ziyadeh FN. The emerging role of transforming growth factor-β in kidney disease. Am J Physiol. 1994;226:F829–F842
  35. Border WA, Noble NA. Interactions of transforming growth factor-β and angiotensin II in renal fibrosis. Hypertension. 1998;31:181–188
  36. Tsao T, Fawcett J, Fervenza FC, et al.  Expression of insulin-like growth factor-1 and transforming growth factor-β in hypokalemic nephropathy in the rat. Kidney Int. 2001;59:96–105
  37. Fine LG, Holley RW, Nasri H, et al.  BCS-1 growth inhibitor transforms a mitogenic stimulus into a hypertrophic stimulus for renal proximal tubular cells: Relationship to Na+/H+ antiport activity. Proc Natl Acad Sci USA. 1985;82:6163–6166
  38. Mujais SK. Collecting duct changes in potassium depletion: effects of ACE inhibition. Am J Physiol. 1994;266:F419–F424
  39. Paller MS, Linas SL. Hemodynamic effects of alterations in potassium. Hypertension. 1982;4:III20–III26
  40. Luke RG, Lyerly R, Andreson J, et al.  Effects of potassium depletion on renin release. Kidney Int. 1982;21:14–19
  41. Timmermans PB, Wong PC, Chiu AT, et al.  Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45:205–251
  42. Huckle WR, Earp HS. Regulation of cell proliferation and growth by angiotensin II. Prog Growth Factor Res. 1994;5:177–194
  43. Scheidegger KJ, Du J, Delafontaine P. Distinct and common pathways in the regulation of insulin-like growth factor-1 receptor gene expression by angiotensin II and basic fibroblast growth factor. J Biol Chem. 1999;274:3522–3530
  44. Brink M, Chrast J, Price SR, et al.  Angiotensin II stimulates gene expression of cardiac insulin-like growth factor I and its receptor through effects on blood pressure and food intake. Hypertension. 1999;34:1053–1059
  45. Brink M, Wellen J, Delafontaine P. Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism. J Clin Invest. 1996;97:2509–2516
  46. Rosenthal SM, Brown EJ, Brunetti A, et al.  Fibroblast growth factor inhibits insulin-like growth factor-II (IGF-II) gene expression and increases IGF-I receptor abundance in BC3H-1 muscle cells. Mol Endocrinol. 1991;5:678–684
  47. McKay A, Poirier C, Peterson L. Converting-enzyme inhibition abolishes polydipsia induced by dietary NaCl and K depletion. Am J Physiol. 1990;258:F1164–F1172
  48. Suga S-I, Kang D-H, Mazzali M, et al.  Angiotensin (Ang) II blockade ameliorates tubulointerstitial injury (TII) induced by chronic potassium (K+)-deficiency. J Am Soc Nephrol. 2000;11:372A; (abstr)
  49. Janicki RH. Renal adaptation during chronic NH4Cl acidosis in the rat: No role for hyperplasia. Am J Physiol. 1970;219:613–618
  50. Nath KA, Salahudeen AK. Induction of renal growth and injury in the intact rat kidney by dietary deficiency of antioxidants. J Clin Invest. 1990;86:1179–1192
  51. Tannen RL. Relationship of renal ammonia production and potassium homeostasis. Kidney Int. 1977;11:453–465
  52. Adam WR, Koretsky AP, Weiner MW. 31P-NMR in vivo measurement of renal intracellular pH: Effects of acidosis and K+ depletion in rats. Am J Physiol. 1986;251:F904–F910
  53. Good DW, Burg MB. Ammonia production by individual segments of the rat nephron. J Clin Invest. 1984;73:602–610
  54. Seifer JL, Harris RC. Chronic K depletion increases Na-H exchange in rat renal cortical brush border membrane vesicles. Kidney Int. 1984;25:282
  55. Nath KA, Hostetter MK, Hostetter TH. Pathophysiology of chronic tubulo-interstitial disease in rats, interaction of dietary acid load, ammonia and complement component C3. J Clin Invest. 1985;76:667–675
  56. Wickham JEA, Shama GP. Endogenous ammonia formation in experimental renal ischaemia. Lancet. 1965;i:195–198
  57. Preuss HG, Murdough HV. The toxic effect of ammonia on renal cortical tubule function in vitro. J Lab Clin Med. 1968;71:561–572
  58. Fitzpatrick JM, Monson JRT, Gunter PA, et al.  Renal accumulation of ammonia: The cause of post-ischaemic functional loss and the “Blue Line”. Br J Urol. 1982;54:608–612
  59. Throssell D, Brown J, Harris KPG, et al.  Metabolic acidosis does not contribute to chronic renal injury in the rat. Clin Sci. 1995;89:64–160
  60. Rabkin R, Palathumpat M, Tsao T. Ammonium chloride alters renal tubular cell growth and protein turnover. Lab Invest. 1993;68:427–438
  61. Zieve L. Regenerative enzyme activity of the liver after partial hepatectomy or toxic injury depressed by continuous NH4 infusion. J Lab Clin Med. 1989;114:527–530
  62. Ray PEE, Castren EJ, Ruley EJ, et al.  Different effects of chronic Na, CI, and K depletion on brain vasopressin mRNA and plasma vasopressin in young rats. Cell Mol Neurobiol. 1991;11:277–287
  63. Wang Z, Baird N, Shumaker H, et al.  Potassium depletion and acid-base transporters in rat kidney: Differential effect of hypophysectomy. Am J Physiol. 1997;272:F736–F743
  64. Marckovich D, Wang H, Puttaparthi K, et al.  Chronic K depletion inhibits renal brush border membrane Na/sulfate cotransport. Kidney Int. 1999;55:244–251
  65. Suga S-I, Phillips MI, Kim Y-G, et al.  Potassium deficiency induces renal hypoxia, tubulointerstitial injury and salt-sensitivity. J Am Soc Nephrol. 1999;10:365A; (abstr)
  66. Wuthrich RP. The complex role of osteopontin in renal disease. Nephrol Dial Transpl. 1998;13:2448–2450
  67. Van Buul-Offers SC, Van Kleffens M, Koster JG, et al.  Human insulin-like growth factor (IGF) binding protein-1 inhibits IGF-I-stimulated body growth but stimulates growth of the kidney in Snell dwarf mice. Endocrinology. 2000;141:1493–1499

 Supported by the American Heart Association Western Affiliate (RR) and the Research Service of the Department of Veterans Affairs (RR).

☆☆ Address reprint requests to Fernando C. Fervenza, MD, PhD, Division of Nephrology, Mayo Clinic, 200 First St, SW, Rochester, MN 55905.

PII: S1051-2276(02)00002-X

doi: 10.1053/jren.2002.33511

Journal of Renal Nutrition
Volume 12, Issue 3 , Pages 151-159 , July 2002