Cerebral salt-wasting syndrome (CSWS) has been regarded as a misnomer of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We take the position that CSWS does exist and might be more common than SIADH. Differentiation between groups has been difficult because of overlapping signs, symptoms, and associated diseases. Euvolemia in SIADH and hypovolemia in CSWS may be the only contrasting variables. However, clinical assessment of extracellular volume is accurate in about 50% of these patients. Determination of serum urate and fractional excretion rates of urate can differentiate one group from the other. In both groups, hyponatremia coexists with hypouricemia and increased fractional excretion of urate. When the hyponatremia is corrected by water restriction, hypouricemia and elevated FEurate correct in SIADH but persist in CSWS. Persistent hypouricemia and elevated FEurate were commonly noted with pulmonary and/or intracranial diseases. The absence of intracranial diseases in some patients suggests that renal salt wasting might be a more appropriate term than CSWS. A review of renal/CSWS reveals three studies involving hyponatremic neurosurgical patients who had decreased blood volume, decreased central venous pressure, and inappropriately high urinary sodium concentrations in the majority of them, suggesting that CSWS was more common than SIADH in neurosurgical patients. Evidence for the presence of a plasma natriuretic factor in CSWS is presented.

1.
Schwartz WB, Bennett W, Curelop S: A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 1957;23:529–542.
2.
Peters JP, Welt LG, Sims EAH, Orloff J, Needham J: A salt-wasting syndrome associated with cerebral disease. Trans Assoc Am Physicians 1950;63:57–64.
3.
Nelson PB, Seif SM, Maroon JC, Robinson GA: Hyponatremia in intracranial disease: Perhaps not the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Neurosurg 1981;55:938–941.
4.
Sivakumar V, Rajshekhar V, Chandy MJ: Management of neurosurgical patients with hyponatremia and natriuresis. Neurosurgery 1994;43:269–274.
5.
Wijdick EFM, Vermeulen M, ten Haaf JA, Hijdra A, Bakker WH, van Gijn J: Volume depletion and natriuresis in patients with a ruptured intracranial aneurysm. Ann Neurol 1985;18:211–216.
6.
Wijdick EFM, Vermeulen M, Hijdra A, van Gijn J: Hyponatremia and cerebral infarction in patients with ruptured intracranial aneurysm: Is fluid restriction harmful. Ann Neurol 1985;11:137–140.
7.
Epstein FH, Levitin H, Glaser G, Lavietes P: Cerebral hyponatremia. N Engl J Med 1961;265:513–518.
8.
Carter NW, Rector FC Jr, Seldin DW: Hyponatremia in cerebral disease resulting from the inappropriate secretion of antidiuretic hormone. N Engl J Med 1961;264:67–72.
9.
Goldberg M, Handler JS: Hyponatremia and renal wasting of sodium in patients with malfunction of the central nervous system. N Engl J Med 1960;263:1037–1043.
10.
Cooper WC, Green IJ, Wang S: Cerebral salt wasting associated with the Guillain-Barré syndrome. Arch Intern Med 1965;116:113–119.
11.
Vogal JHK: Aldosterone in the cerebral salt wasting. Circulation 1963;127:44–50.
12.
Al-Mufti H, Arieff AI: Hyponatremia due to cerebral salt-wasting syndrome: Combined cerebral and distal tubular lesion. Am J Med 1984;77:740–746.
13.
Robertson GL, Athar S: The interaction of blood osmolality and blood volume in regulating plasma vasopressin in man. J Clin Endocrinol Metab 1976;42:613–620.
14.
Chung HM, Kluge R, Schrier RW, Anderson RJ: Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med 1987;83:905–908.
15.
Oliver WJ, Cohen EL, Neel JV: Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a ‘no-salt’ culture. Circulation 1975;52:146–151.
16.
Nowaczynski W, Oliver WJ, Neel JV: Serum aldosterone and protein binding variables in Yanomamo Indians: A ‘no-salt’ culture as compared to partially acculturated Guaymi Indians. Clin Physiol Biochem 1985;3:289–306.
17.
Valtin H: Renal dysfunction: Disorders of Na+ balance. Edema. In: Mechanism Involved in the Fluid and Solute Imbalance. Boston, Little, Brown, 1997, pp 58–59.
18.
Strauss MB, Lamdin E, Smith P, Bleifer DJ: Surfeit and deficit of sodium. Arch Intern Med 1958;102:527–536.
19.
Hollenberg NK: Set point for sodium homeostasis: Surfeit, deficit, and their implication. Kidney Int 1980;17:423–429.
20.
Braunwald E, Planth WH, Morrow AG: A method for the detection and quantification of impaired sodium excretion: Result of an oral sodium tolerance test in normal subjects and in patients with heart disease. Circulation 1965;32:223–231.
21.
Kassirer JP, Schwartz WB: The response of normal man to selective depletion of hydrochloric acid. Am J Med 1966;40:10–18.
22.
Fichman MP, Michelakis AM, Horton R: Regulation of aldosterone in the syndrome of inappropriate antidiuretic hormone secretion (SIADH). J Clin Endocrinol Metab 1974;39:136–144.
23.
Atarashi K, Franco-Saenz R, Mulrow PJ, Snajdar RM, Rapp JP: Inhibition of aldosterone production by atrial natriuretic factor. J Hypertens 1984;2(suppl):293–295.
24.
Maack T, Marion DN, Camargo MJ, Kleinert HD, Laragh JH, Vaughan ED Jr, Atlas SA: Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs. Am J Med 1984;77:1069–1075.
25.
Welt LG, Sims EAH, Orloff J, Needham J: A salt-wasting syndrome associated with cerebral disease. Trans Assoc Am Physicians 1950;63:57–64.
26.
Cort JH: Cerebral salt wasting. Lancet 1974;i:752–754.
27.
Rees JR, Rosalki SB, Maclean ADW: Hyponatremia and impaired renal tubular function with carcinoma of bronchus. Lancet 1960;ii:1005–1009.
28.
Maroon JC, Nelson PB: Hypovolumia in patients with subarachnoid hemorrhage: Therapeutic implications. Neurosurgery 1979;4:223–226.
29.
Nelson PB, Seif S, Gutal J, Robinson AG: Hyponatremia and natriuresis following subarachnoid hemorrhage in a monkey model. J Neurosurg 1984;60:233–237.
30.
Levy ML, Giannotta SL: Induced hypertension and hypervolemia for treatment of cerebral vasospasm. Neurosurg Clin N Am 1990;1:357–365.
31.
Kosnik EJ, Hunt WE: Postoperative hypertension in the management of patients with intracranial arterial aneurysms. J Neurosurg 1976;45:148–154.
32.
Pritz MB: Treatment of cerebral vasospasm: Usefulness of Swan-Ganz catheter monitoring of volume expansion. Surg Neurol 1984;21:239–244.
33.
Sundt TM Jr: Management of ischemic complications after subarachnoid hemorrhage. J Neurosurg 1975;43:418–425.
34.
Yamaki T, Tanooka A, Takahashi A, Imaizumi T, Suetake K, Hashi K: Cerebral salt wasting syndrome distinct from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Acta Neurochir 1992;115:156–162.
35.
Vingerhoets F, de Tribolet N: Hyponatremia hypo-osmolarity in neurosurgical patients: ‘Appropriate secretion of ADH’ and ‘cerebral salt wasting syndrome’. Acta Neurochir (Wien) 1998;91:50–54.
36.
Rapoport S, West CD, Brodysky WA: Salt losing condition; The renal defect in tubercular meningitis. J Lab Clin Med 1950;37:550–561.
37.
Andrew B, Fitzgerald PA, Tyrell JB, Wilson CB: Cerebral salt wasting after pituitary exploration and biopsy: Case report. Neurosurgery 1986;18:469–471.
38.
Oster JR, Perez GO, Larios O, Emary WE, Bourgoignie JJ: Cerebral salt wasting in a man with carcinomatous meningitis. Arch Intern Med 1983;143:2187–2188.
39.
McCrory WW, Macaulay D: Idiopathic hyponatremia in an infant with diffuse cerebral damage. Pediatrics 1957;20:23–32.
40.
Tanneau RA, Pennec YL, Jouquan J, Le Menn G: Cerebral salt wasting in elderly persons. Ann Intern Med 1987;107:120.
41.
Poon WS, Lolin YI, Yeung TF, Yip CP, Goh KY, Lam MK, Cockram C: Water and sodium disorders following surgical excision of pituitary region tumours. Acta Neurochir (Wien) 1996;138:921–927.
42.
Skott O, Briggs JP: Direct demonstration of macula densa mediated renin secretion. Science 1987;37:1618–1620.
43.
Tanneau RS: Hypouricemia with high urate clearance in hyponatremia: Is it always a clue for increased effective volemia? Clin Nephrol 1995;44:128.
44.
Ishikawa S, Saito T, Kaneko K, Okada K, Kuzuya T: Hyponatremia response to fludrocortisone acetate in elderly patients after head injury. Ann Intern Med 1987;106:187–191.
45.
Maesaka JK, Batuman V, Yudd M, Salem M. Sved AF, Venkatesan J: Hyponatremia and hypouricemia: Differentiation from SIADH. Clin Nephrol 1990;33:174–178.
46.
Shannon JA: Glomerular filtration and urea excretion in relation to urine flow in the dog. Am J Physiol 1936;117:206–225.
47.
Goldstein MH, Lenz PR, Levitt MF: Effect of urine flow rate on urea reabsorption in man: Urea as a ‘tubular marker’. J Appl Physiol 1969;26:594–599.
48.
Beck LH: Hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 1979;301:528–530.
49.
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.
50.
Sonnenblick M, Rosin A: Increased uric acid clearance in the syndrome of inappropriate secretion of antidiuretic hormone. Isr J Med Sci 1998;24:20–23.
51.
Osterlind K, Hansen M, Dombernowsky P: Hypouricaemia and inappropriate secretion of antidiuretic hormone in small cell bronchogenic carcinoma. Acta Med Scand 1981;209:289–291.
52.
Sorensen JB, Osterlind K, Kristjansen PEG, Hammer M, Hansen M: Hypouricemia and urate excretion in small cell lung carcinoma patients with syndrome of inappropriate antidiuresis. Acta Oncol 1988;27:351–355.
53.
Weinberger A, Santo M, Solomon F, Shalit M, Pinkhas J, Sperling O: Abnormality in renal urate handling in the syndrome of inappropriate secretion of antidiuretic hormone. Isr J Med Sci 1982;18:711–713.
54.
Shichiri M, Shinoda T, Kijima Y, Shiigai T, Kanayama M: Renal handling of urate in the syndrome of inappropriate secretion of antidiuretic hormone. Arch Intern Med 1985;145:2045–2047.
55.
Assadi FK, John EG: Hypouricemia in neonates with syndrome of inappropriate secretion of antidiuretic hormone. Pediatr Res 1985;19:424–427.
56.
Michelis MF, Warms PC, Fusco RD, Davis BB: Hypouricemia and hyperuricosuria in Laennec cirrhosis. Arch Intern Med 1974;134:681–683.
57.
Boer WH, Koomans HA, Dorhout Mees EJ: Lithium clearance during the paradoxical natriuresis of hypotonic expansion in man. Kidney Int 1987;32:376–381.
58.
Decaux G, Namias B, Gulbis B, Soupart A: Evidence in hyponatremia related to inappropriate secretion of ADH that V1 receptor stimulation contributes to the increase in renal uric acid clearance. J Am Soc Nephrol 1996;7:805–810.
59.
Maesaka JK, Fishbane S: The regulation of renal urate excretion: A critical review. Am J Kidney Dis, in press.
60.
Steele TH: Evidence for altered renal urate reabsorption during changes in volume of the extracellular pyrazinamide suppression of the uricosuric response to sodium chloride infusion. J Lab Clin Med 1974;83:417–427.
61.
Diamond H, Meisel A: Influence of volume expansion, serum sodium, and fractional excretion of sodium on urate excretion. Pflügers Arch 1975;356:47–57.
62.
Cannon PJ, Svahn DS, Demartini FE: The influence of hypertonic saline infusions upon the fractional reabsorption of urate and other ions in normal and hypertensive man. Circulation 1970;41:97–108.
63.
Manuel MA, Schwartz WB, Bennett W, Curelop S: A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 1957;23:529–542.
64.
Maesaka JK, Cusano AJ, Thies HL, Siegal FP, Dreisbach AW: Hypouricemia in acquired immunodeficiency syndrome. Am J Kidney Dis 1990;15:252–257.
65.
Cusano A, Thies HL, Siegal FP, Dreisbach AW, Maesaka JK: Hyponatremia in patients with acquired immune deficiency syndrome. J Acquir Immune Defic Syndr 1990;3:949–953.
66.
Maesaka JK, Venkatesan J, Piccione JM, Decker R, Dreisbach AW, Wetherington JD: Abnormal urate transport in patients with intracranial disease. Am J Kidney Dis 1992;19:10–15.
67.
Ramsdell CM, Kelley WN: The clinical significance of hypouricemia. Ann Intern Med 1973;78:239–242.
68.
Yanase M, Nakahama H, Mikami H, Fukuhara Y, Orita Y, Yoshikawa H: Prevalence of hypouricemia in an apparently normal population. Nephron 1988;48:80.
69.
Maesaka JK, Venkatesan 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.
70.
Maesaka JK, Wolf-Klein G, Piccione JM, Ma CM: Hypouricemia, abnormal renal tubular urate transport, and plasma natriuretic factor(s) in patients with Alzheimer’s disease. J Am Geriatr Soc 1993;41:501–506.
71.
Rudman D, Racette D, Rudman IW, Mattson DE, Erve PR: Hyponatremia in tube-fed elderly men. J Chronic Dis 1986;39:73–80.
72.
Sorensen PS: Studies of vasopressin the human cerebrospinal fluid. Acta Neurol Scand 1986;74:81–102.
73.
Norbiato G, Bevilacqua M, Carella F, Chebat E, Raggi U, Bertora P, Grassi MP, Mangoni A: Alterations in vasopressin regulation in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1988;51:903–908.
74.
Epstein M, Hollenberg NK: Age as a determinant of renal sodium conservation in normal man. J Lab Clin Med 1976;87:411–417.
75.
Maesaka JK: Expanded view of SIADH, hyponatremia and hypouricemia. Clin Nephrol 1996;46:79–83.
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