Background/AIMS: Hyponatremia secondary to distal diuretics intake could have a biochemical picture similar to the one observed in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In these patients, water retention is considered to be the main causal factor and solute depletion a secondary one. Methods. We compared the level of cation (Na + K) depletion and water balance in patients with high or low uric acid levels (< 4 mg/dL or 238 µmol/L) or with high or low (< 30 mg/dL or 5 mmol/L) urea levels. Data were collected from 15 consecutive patients treated in a similar way by a daily infusion of 2 L isotonic saline with potassium chloride until SNa reached at least 132 mmol/L. The same procedure was performed in 6 patients with hyponatremia due to salt depletion not related to diuretic intake. Results: Hyponatremia, associated with low or high uric acid level is mainly due to severe cation depletion (around 600 mmol) and not due to water retention, since body weight did not change significantly (SNa 122 ± 2.0 mEq/L). If patients were classified according to serum urea levels those with higher urea levels (≥30 mg/dL) presented with a mild increase in BW (0.84 ± 0.37 kg). In patients with salt depletion and hyponatremia not related to diuretic intake, we observe as expected an increase in BW (1.5 ± 0.3 kg) and similar cation retention with the treatment. Conclusion: We therefore suggest that diuretic induced hyponatremia with an SIADH-like biochemical profile, should be treated mainly by solute -repletion.

Keywords:
Hyponatremia, Secretion of antidiuretic hormone, Thiazide, Uric acid
1.
Sonnenblick M, Rosin AJ: Significance of the measurement of uric acid fractional clearance in diuretic induced hyponatraemia. Postgrad Med J 1986; 62: 449–452.
2.
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: 102–108.
3.
Fenske W, Stork S, Koschker AC, Blechschmidt A, Lorenz D, Wortmann S, Allolio B: Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics. J Clin Endocrinol Metab 2008; 93: 2991–2997.
4.
Decaux G, Genette F, Mockel J: Hypouremia in the syndrome of inappropriate secretion of antidiuretic hormone. Ann Intern Med 1980; 93: 716–717.
5.
Musch W, Verfaillie L, Decaux G. Age-related increase in plasma urea level and decrease in fractional urea excretion: clinical application in the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol 2006; 1: 909–914.
6.
Beck LH: Hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 1979; 301: 528–530.
7.
Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al: Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 2014; 29(suppl 2): i1–i39.
8.
Liamis G, Christidis D, Alexandridis G, Bavraktari E, Madias NE, Elisaf M: Uric acid homeostasis in the evolution of diuretic-induced hyponatremia. J Invest Med 2007; 55: 36–44.
9.
Musch W, Decaux G: Utility and limitations of biochemical parameters in the evaluation of hyponatremia in the elderly. Int Urol Nephrol 2001; 32: 475–493.
10.
Musch W, Decaux G: Treating the syndrome of inappropriate ADH secretion with isotonic saline. QJM 1998; 69: 749–753.
11.
Decaux G: Difference in solute excretion during correction of hyponatremic patients with cirrhosis or syndrome of inappropriate secretion of antidiuretic hormone by oral vasopressin V2 receptor antagonist VPA-985. J Lab Clin Med 2001; 138: 18–21.
12.
Decaux G, Prospert F, Soupart A, Musch W. Evidence that chronicity of hyponatremia contributes to the high urate clearance observed in the syndrome of inappropriate antidiuretic hormone secretion. Am J Kid Dis 2000; 36: 745–751.
13.
Decaux G, Unger J, Brimioulle S, Mockel J: Hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Rapid correction with urea, sodium chloride, and water restriction therapy. JAMA 1982; 247: 471–474.
14.
Namias B, Soupart A, Kornreich A, Decaux G. In human patients, vascular water retention during DDAVP-related hyponatremia occurs mainly in the plasma volume and not in the erythrocyte. J Lab Clin Med 1996; 128: 612–617.
15.
Tarazi RC, Dustan HP, Erohlich ED: Long-term thiazide therapy in essential hypertension. Evidence for persistent alteration in plasma volume and renin activity. Circulation 1970; 41: 709–717.
16.
Clark BA, Shannon RP, Rosa RM, Epstein FH: Increased susceptibility to thiazide-induced hyponatremia in the elderly. J Am Soc Nephrol 1994; 5: 1106–1111.
17.
Musch W, Xhaet O, Decaux G: Solute loss plays a major role in polydipsia-related hyponatraemia of both water drinkers and beer drinkers. QJM 2003; 96: 421–426.
18.
Steele A, Gowrishankar M, Abrahamson S, Mazer CD, Feldman RD, Halperin ML: Postoperative hyponatremia despite near-isotonic saline infusion: a phenomenon of desalination. Ann Intern Med 1997; 126: 20–25.
19.
Hoc JK, Silver S, Stern RH: Diuretic-associated hyponatremia. Sem Nephrol 2011; 31: 553–566.
20.
Liamis G, Filippatos TD, Elisaf MS: Thiazide-associated hyponatremia in the elderly: what the clinician needs to know. J Geriatr Cardiol 2016; 13: 175–182.
21.
Ware JS, Wain LV, Channowajjhala SK, et al: Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia. J Clin Invest 2017; 127: 3367–3374.
22.
Frenkel NJ, Vogt L, De Rooij SE, Trimpert C, Levi MM, Deen PM, Van den Born BJ: Thiazide-induced hyponatraemia is associated with increased water intake and impaired urea-mediated water excretion at low plasma antidiuretic hormone and urine aquaporine-2. J Hypertens 2015; 33: 627–633.
23.
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.
24.
Kim GH, Lee JW, Oh YK, Chang HR, Joo KW, Na KY, Earm JH, Knepper MA, Han JS: Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. J Am Soc Nephrol 2004; 15: 2836–2843.
25.
Sonnenblick M, Friedlander Y, Rosin AJ: Diuretic-induced severe hyponatremia. Review and analysis of 129 reported patients. Chest 1993; 103: 601–606.
26.
Gowrishankar M, Chen CB, Mallie JP, Halperin ML: What is the impact of potassium excretion on the intracellular fluid volume: importance of urine anions. Kidney Int 1996; 50: 1490–1495.
27.
Maesaka JK, Fishbane S: Regulation of renal urate excretion: a critical review. Am J Kid Dis 1998; 32: 917–933.
28.
Roch-Rasuel F, Gursan B, Schild L: Indirect coupling of urate and p-aminohippurate transport to sodium in human brush-border membrane vesicules. Am J Physiol 1996; 270(1 pt 2):F61–F68.
29.
Bruno CM, Pricoco G, Cantone D, Marino E, Bruno F: Tubular handling of uric acid factors influencing its renal excretion: a short review. EMJ Nephrol 2016; 4: 92–97.
30.
Esparza Martin N, García Nieto V: Hypouricemia and tubular transport of uric acid. Nephrologia 2011; 31: 44–50.
31.
Decaux G: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Semin Nephrol 2009; 29: 239–256.
32.
Sterns RH: Disorders of plasma sodium-causes, consequences, and correction. N Engl J Med 2015; 373: 55–65.
33.
Bhaue G, Neilson EG: Body fluid dynamics: back to the future. J Am Soc Nephrol 2011; 22: 2166–2181.
34.
Sperling O: Uric acid; in: Scriver CR, Beaudet AL, Sky WS, Valle D (eds): The Metabolic Basis of Inherited Disease (ed 6). New York, Mc Graw Hill, 1989, pp 2605–2619.
35.
Yanase M, Nakahama H, Mikami H, Fukuhara Y, Orita Y, Yoshikawa H: Prevalence of hypouricemia in apparently normal population. Nephron 1988; 48: 80.
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.