Skip to main content
SpringerLink
Log in

Utility and limitations of biochemical parameters in the evaluation of hyponatremia in the elderly

  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

We evaluated in 110 consecutive elderly hyponatremic patients the value of traditional clinical and biochemical data and the place of a test infusion of 2 liters isotonic saline over 24 hours, in establishing the etiology of the hyponatremia. The causes of hyponatremia were as follows: 31% SIADH patients, 23% patients with hyponatremia due to diuretics, 18% potomania patients, 15%salt depleted patients, 5% salt depleted SIADH patients, 5%patients with a salt loosing syndrome and 3% patients with hyponatremia of unknown origin. Several salt depleted (SD) and SIADH patients could be confounded. Usually, adults with SIADH show plasma uric acid values <4 mg/dL. In our elderly population, 41% of SD patients presented plasma uric acid <4mg/dL, while 27% of SIADH patients showed plasma uric acid >4mg/dL. Eighty-two percent of SD patients appeared to have plasma urea levels >30 mg/dL, but this was also the case in 21% of SIADH patients. Twenty-nine of the SD patients presented a urinary sodium >30 mEq/L, but all had fractional sodium excretion (FENa) lower than 0.5%. However, in SIADH, 42% of the patients presented also FENa <0.5%. Fractional excretion of urea (FE urea) below 50%was encountered in 82% of SD patients and FE urea above 50% in only 52% of the SIADH patients. Plasma renin and aldosterone values were poorly discriminative. A test infusion with 2 liters isotonic saline over 24 hours allowed a correct classification of all the patients. In about 2/3 of the population, administration of isotonic saline could be considered as useful (SD, most diuretic patients, potomania patients, salt loosing syndrome patients and some SD SIADH patients). A plasma sodium (Pna) increase of at least 5 mEq/L 24 hours after saline infusion has been suggested as highly suggestive of SD. Nevertheless, 29% of our SD patients did not increase their PNa level by 5 mEq/L or more,while 30% of our SIADH patients did. PNa improved after 2 liters isotonic saline over 24 hours in 90 patients (85%) as opposed to12 others (9 SIADH and 3 diuretic patients), decreasing their plasma sodium. The isotonic saline infusion test, only allows a reliable classification of hyponatremia, as far as both PNa and sodium excretion were taken into account. In the SIADH group, 6 patients (5%) presented initially manifest solute depletion and retained the 2 liters isotonic saline before developping inappropriate natriuresis. Six patients showed a transient salt loosing syndrome with high fractional potassium excretion (FEK) and high calciuria, which differentiates them from thiazide patients presenting also high FEK, but low calciuria. These patients were also polyuric at admission. The saline infusion was well tolerated in all but 2 patients, developping mild pulmonary congestion at the end of the test infusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anderson RJ, Chung HM, Kluge R, Schrier RW. Hyponatremia: A prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 1985; 102: 164–168.

    PubMed  CAS  Google Scholar 

  2. Hochman I, Cabili S, Peer G. Hyponatremia in internal medicine ward patients: Causes, treatment and prognosis. Isr JMed Sci 1989; 25: 73–76.

    CAS  Google Scholar 

  3. Kennedy PGE, Mitchell DM, Hoffbrand BI. Severe hyponatremia in hospitalized in-patients. Br Med J 1978; 2: 1251–1253.

    PubMed  CAS  Google Scholar 

  4. Tierney WM, Martin DK, Greenlee MC, Zerbe RL, McDonald CJ. The prognosis of hyponatremia at hospital admission. J Gen Intern Med 1986; 1: 380–385.

    PubMed  CAS  Google Scholar 

  5. Kleinfeld M, Casimir M, Borra S. Hyponatremia as observed in a chronic disease facility. J Am Geriatr Soc 1979; 27: 156–161.

    PubMed  CAS  Google Scholar 

  6. Sunderam SG, Mankikar GD. Hyponatremia in the elderly. Age Ageing 1983; 12: 77–80.

    PubMed  CAS  Google Scholar 

  7. Soupart A, Decaux G. Therapeutic recommendations for management of severe hyponatremia: Current concepts on pathogenesis and prevention of neurologic complications. Clin Nephrol 1996; 46(3): 149–169.

    PubMed  CAS  Google Scholar 

  8. Beck LH. Changes in renal function with aging. Clinics in Geriatric Medicine 1998; 14(2): 199–209.

    PubMed  CAS  Google Scholar 

  9. Miller M. Hormonal aspects of fluid and sodium balance in the elderly. In: Gambert SR, Gupta KL, editors. Endocrinology and metabolism clinics of North America, vol. 24, no.2. Philadelphia: W.B. Saunders, 1995: 233–253.

    Google Scholar 

  10. Noth RH, Mazzaferri EL. Age and the endocrine system. Clin Geriatr Med 1985; 1(1): 223–250.

    PubMed  CAS  Google Scholar 

  11. Miller M, Hecker MS, Friedlander DA, Carter JM. Apparent idiopathic hyponatremia in an ambulatory geriatric population. J Am Geritr Soc 1996; 44(4): 404–408.

    CAS  Google Scholar 

  12. Rose BD. Hypoosmolal states-hyponatremia. In: Jeffers JD, Navrozov M, editors. Clinical physiology of acid-base and electrolyte disorders. New York: McGraw-Hill, 1994: 651–694.

    Google Scholar 

  13. Gross PA, Kettler M, Hausmann C, Ritz E. The chartered and unchartered waters of hyponatremia. Kidney Int 1987; 32(suppl 21): S67.

    Google Scholar 

  14. Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical assesment of extracellular fluid volume in hyponatremia. Am J Med 1987; 83: 905–908.

    Article  PubMed  CAS  Google Scholar 

  15. Musch W, Thimpont J, Vandervelde D, Verhaeverbeke I, Berghmans T, Decaux G. Combined fractional excretion of sodium and urea better predicts the response to saline in hyponatremia than do usual clinical and biochemical parameters. Am J Med 1995; 99: 348–355.

    Article  PubMed  CAS  Google Scholar 

  16. Musch W, Decaux G. Treating the syndrome of inappropriate ADH secretion with isotonic saline. Q J Med 1998; 91: 749–753.

    CAS  Google Scholar 

  17. Maesaka JK, Vankatesan J, Piccione JM, Decker R, Dreisbach AW, Wetherington J. Plasma natriuretic factor(s) in patients with intracranial disease, renal salt wasting and hyperuricosuria. Life Sci 1993; 52: 1875–1882.

    Article  PubMed  CAS  Google Scholar 

  18. Michelis MF, Warms PC, Fusco RD, Davis BB. Hypouricemia and hyperuricasuria in laennec' cirrlosis. Arch Intern Med 1974; 134: 681–683.

    Article  PubMed  CAS  Google Scholar 

  19. Decaux G, Dumont I, Naele N, Mols P, Melot C, Mockel J. High uric acid and urea clearance in cirrhosis secundary to increased ‘effective vascular volume'. Am J Med 1982; 73: 328–334.

    Article  PubMed  CAS  Google Scholar 

  20. Decaux G, Prospert F, Namias B, Schlesser M, Soupart A. Raised urea clearance in cirrhotic patients with high uric acid clearance is related to low salt excretion. Gut 1992; 33(8): 1105–1108.

    PubMed  CAS  Google Scholar 

  21. Decaux G, Schlesser M, Coffernils M, Prospert F, Namias B, Brimioulle S, Soupart A. Uric acid, anion gap and urea concentration in the diagnostic approach to hyponatremia. Clin Nephrol 1994; 42(2): 102–108.

    PubMed  CAS  Google Scholar 

  22. Beck LH. Hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone. NEJM 1979; 301: 528–530.

    PubMed  CAS  Google Scholar 

  23. Decaux G, Van Laethem Y, Van Kuyck M, Mockel J. Hypercalciuria in the syndrome of inappropriate secretion of antidiuretic hormone. Mineral and Electrolyte Metab 1982; 7: 192–196.

    CAS  Google Scholar 

  24. Mallie JP, Chevet D, Jeandel C. Defective post-diuretic antinatriuresis in the aging kidney: A possible explanation for thiazide-induced hyponatremia in the elderly. Geriatric Nephrol and Urol 1995; 4: 153–160.

    Article  Google Scholar 

  25. Hegstad R, Brown RD, Jiang NS. Aging and aldosterone. Am J Med 1983; 74: 442–448.

    Article  PubMed  CAS  Google Scholar 

  26. Decaux G, Namias B, Soupart A, Musch W. Evidence to suggest that hyponatremia by itself contributes to the high urate clearance in the SIADH. Am J Kidney Dis 2000; 36N4: 745–751.

    Google Scholar 

  27. Dorhout Mees EJ, Blom van Assendelf TP, Nieuwenhuis MG. Elevation of uric acid clearance caused by inappropriate antidiuretic hormone secretion. Acta Med Scand 1971; 189: 69–72.

    Article  PubMed  CAS  Google Scholar 

  28. Decaux G, Dumont I, Waterlot Y, Hanson B. Mechanisms of hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone. Nephron 1985; 39: 164–168.

    PubMed  CAS  Google Scholar 

  29. Prospert F, Soupart A, Brimioulle S, Decaux G. Evidence of defective tubular reabsorbtion and normal secretion of uric acid in the syndrome of inappropriate secretion of antidiuretic hormone. Nephron 1993; 64(2): 189–192.

    PubMed  CAS  Google Scholar 

  30. Decaux G, Genette F, Mockel J. Hypouremia in the syndrome of inappropriate secretion of antidiuretic hormone. Ann Intern Med 1980; 93: 716–717.

    PubMed  CAS  Google Scholar 

  31. Decaux G, Prospert F, Cauchie P, Soupart A. Dissociation between uric acid and urea clearances in the syndrome of inappropriate secretion of antidiuretic hormone related to salt excretion. Clin Sci (Colch) 1990; 78: 451–455.

    CAS  Google Scholar 

  32. Braghiroli A, Sacco C, Erbetta M, Ruga V, Donner CF. Overnight urinary uric acid: creatinine ratio for detection of sleep hypoxemia. Validation study in chronic obstructive pulmonary disease and obstructive sleep apnea before and after treatment with nasal continuous positive airway pressure. Am Rev Respir Dis 1993; 148(1): 173–178.

    PubMed  CAS  Google Scholar 

  33. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967; 42: 790–806.

    Article  PubMed  CAS  Google Scholar 

  34. Mudge GH, Berndt WO, Valtin H. Tubular transport of urea, glucose, phosphate, uric acid, sulfate and thiosulfate. In: Orloff J, Berliner RW, Geiger SR, editors. Handbook of Physiology, Section 8. Washington, DC: American Physiological Society, 1973: 587–652.

    Google Scholar 

  35. Goldstein MH, Lenz PR, Levitt MF. Effect of urine flow rate on urea reabsorbtion in man: Urea as a ‘tubular marker'. J Appl Physiol 1969; 26(5): 594–599.

    PubMed  CAS  Google Scholar 

  36. Werbel SS, Ober KP. Acute adrenal insufficiency. In: Ober KP, guest editor. Endocrinology and metabolism clinics of North America: Endocrine crises, vol. 22, no.2. Philadelphia: Saunders, 1993: 303–328.

    Google Scholar 

  37. Derosa G, Corsello SM, Cechini L. Clinical study of Addison' disease. Exp Clin and Metab 1987; 90: 232–242.

    CAS  Google Scholar 

  38. Nerup J. Addison' disease - a review of some clinical, pathological, and immunological features. Dan Med Bull 1974; 21: 201–217.

    PubMed  CAS  Google Scholar 

  39. Ahmed AB, George BC, Conyalez-Auvert C, Dingman JF. Increased plasma arginine vasopressin in clinical adrenocortical insufficiency and its inhibition by glucosteroids. J Clin Invest 1967; 46(1): 111–123.

    PubMed  CAS  Google Scholar 

  40. Green HH, Harrington AR, Valtin H. On the role of antidiuretic hormone in the inhibition of acute water diuresis in adrenal insufficiency and the effects of gluco-and mineralocorticoids in reversing the inhibition. J Clin Invest 1970; 49: 1724–1736.

    PubMed  CAS  Google Scholar 

  41. Oelkers W. Hyponatremia and inappropriate secretion of vasopressin (antidiuretic hormone) in patients with hypopituitarism. N Engl J Med 1989; 321: 492–496.

    Article  PubMed  CAS  Google Scholar 

  42. Wolfson B, Manning RW, Davis LG, Arentzen R, Baldino F Jr. Co-localisation of corticotropin releasing factor and vasopressin in RNA in neurons after adrenalectomy. Nature 1985; 315: 59–61.

    Article  PubMed  CAS  Google Scholar 

  43. Decaux G, Crenier L, Namias B, Gervy C, Soupart A. Normal acid-base equilibrium in acute hyponatremia induced by arginine vasopressin or 1–deamino-8–D-arginine vasopressin in rats. J Lab Clin Med 1994; 123: 892–898.

    PubMed  CAS  Google Scholar 

  44. Cohen JJ, Hulter HN, Smithline N, Melby JC, Schwartz WB. The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. J Clin Invest 1976; 58: 1201–1208.

    PubMed  CAS  Google Scholar 

  45. Decaux G, Crenier L, Namias B, Gervy C, Soupart A. Restoration by corticosteroids of the hyperaldosteronism in hyponatremic rats with panhypopituitarism. Cli Sci 1994; 87: 435–439.

    CAS  Google Scholar 

  46. Skowsky WR, Kikuchi TA. The role of vasopressin in the impaired water excretion of myxoedema. Am J Med 1978; 64: 613–621.

    Article  PubMed  CAS  Google Scholar 

  47. Iwasaki Y, Oiso Y, Yamouchi K. Osmoregulation of plasma vasopressin in myxoedema. J Clin Endocrinol Metab 1990; 70: 534–539.

    Article  PubMed  CAS  Google Scholar 

  48. Koide Y, Oda K, Shimizu K. Hyponatremia without inappropriate secretion of vasopressin in a case of myxoedema coma. Endocrinol Jpn 1982; 29: 363–367.

    PubMed  CAS  Google Scholar 

  49. Ojamaa K, Balkman C, Klein I. Acute effects of triiodothyronine on arterial smooth muscle cells. Ann Thorac Surg 1993; 56: S61.

    Article  PubMed  CAS  Google Scholar 

  50. Allon M, Harrow A, Pasque CB, Rodriguez M. Renal sodium and water handling in hypothyroid patients: The role of renal insufficiency. J Am Soc Nephrol 1990; 1: 205–210.

    PubMed  CAS  Google Scholar 

  51. Hanna MWF, Scanlon MF. Hyponatremia, hypothyroidism, and role of arginine-vasopressin. Lancet 1997; 350: 755–756.

    Article  PubMed  CAS  Google Scholar 

  52. MacLennan WJ. Diuretics in the elderly: How safe? Br Med J 1988; 296: 1551–1552.

    CAS  Google Scholar 

  53. Delaney V, Bourke E. Electrolyte, water and acid base disturbances in the elderly. In: Michelis MF, Davis BB, Preuss HG, editors. Geriatric Nephrology. New York: Field, Rich and Associates, 1986: 40–53.

    Google Scholar 

  54. Mathew TH, Boyd IW, Rohan AP. Hyponatremia due to the combination of hydrochlorothiazide and amiloride (Moduretic): Australian spontaneous report 1977–1988. Med J Australia 1990; 152: 308–309.

    PubMed  CAS  Google Scholar 

  55. Roberts CJ, Mitchell JV, Donley AJ. Hyponatremia: Adverse effect of diuretic treatment. Br Med J 1977; 1: 210.

    Article  PubMed  CAS  Google Scholar 

  56. Ashouri OS. Severe diuretic-induced hyponatremia in the elderly. Arch Intern Med 1986; 146: 1355–1357.

    Article  PubMed  CAS  Google Scholar 

  57. Friedman E, Shadel M, Halkin H, Farfel Z. Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis. Ann Intern Med 1989; 110: 24–30.

    PubMed  CAS  Google Scholar 

  58. Szatalowicz VL, Miller PD, Lacher JW, Gordon JA, Schrier RW. Comparative effects of diuretics on renal water excretion in hyponatremic oedematous disorders. Clin Sci 1982; 62: 235–238.

    PubMed  CAS  Google Scholar 

  59. Ashraf N, Locksley R, Arieff Al. Thiazide-induced hyponatremia associated with death or neurological damage in outpatients. Am J Med 1981; 70: 1163–1168.

    Article  PubMed  CAS  Google Scholar 

  60. Sonnenblick M, Rosin AJ. Significance of the measurement of uric acid fractional clearance in diuretic induced hyponatremia. Postgrad Med J 1986; 62: 449–452.

    PubMed  CAS  Google Scholar 

  61. Elisaf M, Siamopoulos KC. Fractional excretion of potassium in normal subjects and in patients with hypokalemia. Postgrad Med J 1995; 71: 211–212.

    PubMed  CAS  Google Scholar 

  62. Steinmuller SR, Puschet JB. Effects of metolazone in man: Comparison with chlorothiazide. Kidney International 1972; 1: 169–181.

    PubMed  CAS  Google Scholar 

  63. Hariprasad MK, Eisinger RP, Nadler IM, Padmanabhan CS, Nidus BD. Hyponatremia in psychogenic polydipsia. Arch Intern Med 1980; 140: 1639–1642.

    Article  PubMed  CAS  Google Scholar 

  64. Fenves AZ, Thomas S, Knochel JP. Beer potomania: Two cases and review of the literature. Clinical Nephrology 1996; 45(1): 61–64.

    PubMed  CAS  Google Scholar 

  65. Tanneau RS, Pennec YL, Morin JF, Codet JP, Bourbigot B, Garre M, Le Menn G. Salt wastage, plasma volume contraction and hypokalemic paralysis in self-induced water intoxication. Nephron 1993; 64: 570–575.

    Article  PubMed  CAS  Google Scholar 

  66. Demanet JC, Bonnyns M, Bleiberg H, Stevens-Rockmans C. Coma due to water intoxication in beer drinkers. Lancet 1971/2(7734): 1115–1117.

    Article  PubMed  CAS  Google Scholar 

  67. Barlow E, De Wardener HE. Compulsive water drinking. Q J Med 1959; 110: 235–258.

    Google Scholar 

  68. Blaustein DA, Schwenk MH. Beer potomania in a non-beer drinker. Clinical Nephrology 1997; 48(3): 203–204.

    PubMed  CAS  Google Scholar 

  69. Thaler SM, Teitelbaum I, Berl T. ‘Beer potomania’ in non-beer drinkers: effect of low dietary solute intake. Am J Kidney Dis 1998; 31(6): 1028–1031.

    PubMed  CAS  Google Scholar 

  70. Peters JP. A salt wasting syndrome associated with cerebral disease. Trans Assoc Am Physicians 1950; 63: 57–64.

    PubMed  CAS  Google Scholar 

  71. Camargo MJF, Kleinert HD, Atlas SA. Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. Am J Physiol 1984; 246: 447–456.

    Google Scholar 

  72. DeBold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 1981; 28: 89–94.

    Article  CAS  Google Scholar 

  73. Huang CL, Lewicki J, Johnson LK, Cogan MG. Renal mechanism of action of rat atrial natriuretic factor. J Clin Invest 1985; 75: 769–773.

    Article  PubMed  CAS  Google Scholar 

  74. Keeler R, Azzanolo AM. Effects of ANF on renal handling of water and electrolytes in rats. Can J Physiol Pharmacol 1983; 61: 996–1002.

    PubMed  CAS  Google Scholar 

  75. Wallen T, Landahl S, Hedner T, Saito I, Masuda I, Nakao K. Brain natriuretic peptide in an elderly population. J Intern Med 1997; 242: 307–311.

    Article  PubMed  CAS  Google Scholar 

  76. Lindeman RD, Preuss HG. Renal physiology and pathophysiology of aging. In: Michelis MF, Davis BB, Preuss HG, editors. Geriatric nephrology. New York: Field, Rich and Associates, 1986: 5–9.

    Google Scholar 

  77. Delaney V, Bourke E. Electrolyte, water and acid base disturbances in the elderly. In: Michelis MF, Davis BB, Preuss HG, editors. Geriatric nephrology. New York: Field, Rich and Associates, 1986: 40–53.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Bracops Hospital, Brussels, Belgium

    Wim Musch

  2. Research Unit for the Study of Hydromineral Metabolism, Erasme University Hospital, Free University of Brussels, Brussels, Belgium

    Guy Decaux

Authors
  1. Wim Musch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guy Decaux
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Musch, W., Decaux, G. Utility and limitations of biochemical parameters in the evaluation of hyponatremia in the elderly. Int Urol Nephrol 32, 475–493 (2001). https://doi.org/10.1023/A:1017586004688

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1017586004688

Search

Navigation