Anti-diuretic hormone;

What is the role of measuring serum uric acid level in my patient with hyponatremia suspected of having syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

The utility of checking serum uric acid (SUA) in hyponatremia primarily stems from the fact that it helps distinguish SIADH from volume contraction as the cause of hyponatremia.1 Whereas hyperuricemia commonly accompanies volume contraction, hypouricemia is found in the majority (70%) of patients with SIADH.2 This finding is caused by increased urinary excretion of SUA in patients with SIADH.3

There are several potential mechanisms for the association of SIADH with hypouricemia. First, the expanded vascular volume in these patients enhances UA clearance by decreasing its reabsorption, as supported by improved UA serum levels in SIADH patients on fluid restriction.4 Of note, UA normalization with fluid restriction is more pronounced in chronic SIADH patients compared to healthy individuals acutely volume overloaded via treatment with synthetic ADH (i.e. desmopressin).5 This may be due to the fact that, unlike endogenous ADH, desmopressin is a selective agonist of vasopressin 2 receptors (V2R), promoting water reabsorption in the collecting duct without binding to vasopressin 1 receptors (V1R), which promotes UA secretion and inhibits UA reabsorption in the proximal tubule.5,6  To make things worse, there is also evidence that chronic hyponatremia induced by SIADH can directly promote UA excretion!7

Last, keep in mind that salt-wasting disease, a less common cause of hyponatremia, may also be associated with hypouricemia. However, in contrast to patients with SIADH, UA excretion remains high and serum UA levels remain low in these patients even after their hyponatremia is corrected. 8

Bonus Pearl: Did you know that tolvaptan, a selective ADH (V2R) antagonist, has been shown to be effective in raising serum sodium and UA levels in SIADH patients with the caveat that its chronic use may also cause hyperuricemia? 9,10

Contributed by Stella Hoft, PhD, Medical Student, St. Louis University Medical School, St. Louis, Missouri

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References

  1. Liamis G, Christidis D, Alexandridis G, Bairaktari E, Madias NE, Elisaf M. Uric acid homeostasis in the evaluation of diuretic-induced hyponatremia. J Investig Med. 2007 Jan;55(1):36-44. doi: 10.2310/6650.2007.06027. PMID: 17441410. https://journals.sagepub.com/doi/10.2310/6650.2007.06027?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
  2. Decaux G, Musch W. Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol. 2008 Jul;3(4):1175-84. doi: 10.2215/CJN.04431007. Epub 2008 Apr 23. PMID: 18434618. https://journals.lww.com/cjasn/abstract/2008/07000/clinical_laboratory_evaluation_of_the_syndrome_of.38.aspx
  3. Li R, Wu B, Han M, Li M, Yang X, Zhang J, Zhang Y, Liu Y. Uric Acid Metabolic Disorders in Pituitary-Target Gland Axis. Diabetes Metab Syndr Obes. 2024 Feb 7;17:661-673. doi: 10.2147/DMSO.S448547. PMID: 38343584; PMCID: PMC10859102. https://www.dovepress.com/uric-acid-metabolic-disorders-in-pituitary-target-gland-axis-peer-reviewed-fulltext-article-DMSO
  4. Beck LH. Hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med. 1979 Sep 6;301(10):528-30. doi: 10.1056/NEJM197909063011005. PMID: 460306. https://www.nejm.org/doi/abs/10.1056/NEJM197909063011005
  5. 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 May;7(5):805-10. doi: 10.1681/ASN.V75805. PMID: 8738818. https://journals.lww.com/jasn/abstract/1996/05000/evidence_in_hyponatremia_related_to_inappropriate.23.aspx
  6. Taniguchi K, Tamura Y, Kumagai T, Shibata S, Uchida S. Stimulation of V1a receptor increases renal uric acid clearance via urate transporters: insight into pathogenesis of hypouricemia in SIADH. Clin Exp Nephrol. 2016 Dec;20(6):845-852. doi: 10.1007/s10157-016-1248-x. Epub 2016 Mar 2. PMID: 26935049. https://link.springer.com/article/10.1007/s10157-016-1248-x
  7. 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 Kidney Dis. 2000 Oct;36(4):745-51. doi: 10.1053/ajkd.2000.17623. PMID: 11007676. https://www.ajkd.org/article/S0272-6386(00)08495-X/ppt
  8. Momi J, Tang CM, Abcar AC, Kujubu DA, Sim JJ. Hyponatremia-what is cerebral salt wasting? Perm J. 2010 Summer;14(2):62-5. doi: 10.7812/TPP/08-066. PMID: 20740122; PMCID: PMC2912080. https://www.thepermanentejournal.org/doi/10.7812/TPP/08-066
  9. Nagamine T. Uric acid levels with tolvaptan treatment for syndrome of inappropriate antidiuretic hormone secretion. Endocrine. 2024 Mar;83(3):826-827. doi: 10.1007/s12020-023-03612-3. Epub 2023 Nov 20. PMID: 37982946. https://link.springer.com/article/10.1007/s12020-023-03612-3
  10. Bondanelli M, Aliberti L, Gagliardi I, Ambrosio MR, Zatelli MC. Long-term low-dose tolvaptan efficacy and safety in SIADH. Endocrine. 2023 Nov;82(2):390-398. doi: 10.1007/s12020-023-03457-w. Epub 2023 Jul 28. PMID: 37507553; PMCID: PMC10543144. https://link.springer.com/article/10.1007/s12020-023-03457-w

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What is the role of measuring serum uric acid level in my patient with hyponatremia suspected of having syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

What is the significance of hyponatremia in my patient with acute decompensated congestive heart failure (ADCHF)?

FA Manian MD, MPH, , , , , , Leave a comment

Hyponatremia, defined as a serum sodium <135 meq/L, is observed in ~20% of patients hospitalized with ADCHF, and is often dilutional, not “depletional” (ie, not associated with hypovolemia) in this condition1.

In ADCHF, hyponatremia is primarily caused by the production of arginine vasopressin (AVP) (also known as anti-diuretic hormone, or ADH) as a result of decreased perfusion pressures in the aortic arch and renal afferent arterioles, and increased thirst due to the activation of the renin-angiotensin system.  Hyponatremia correlates with the severity of ADCHF and adverse clinical outcomes2.   

 A common approach to dilutional hyponatremia in ADCHF is fluid restriction. Other potential therapies include angiotension converting enzyme inhibitors (by increasing cardiac output and decreasing thirst), loop diuretics (by reducing water reabsorption in the renal distal tubule), and AVP antagonists (eg, tolvapatan, satavaptan)1,3.  Otherwise, in the absence of symptoms, no specific therapy is generally indicated for serum sodium levels ≥ 120mEq/L.

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References 

  1. Verbrugge FH, Steels P, Grieten L, Nijst P, Tang WHW, Mullens W. Hyponatremia in acute decompensated heart failure: Depletion versus dilution. J Am Coll Cardiol 2015;65:480-92. https://www.sciencedirect.com/science/article/pii/S073510971407394X?via%3Dihub
  2. Leier CV, Dei Cas L, Metra M. Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia, and hypomagnesemia. Am Heart J. 1994;128:564.  https://www.sciencedirect.com/science/article/pii/0002870394906335
  3. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C, SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355:2099. https://www.ncbi.nlm.nih.gov/pubmed/17105757

 

Contributed by Ricardo Ortiz, Medical Student, Harvard Medical School

What is the significance of hyponatremia in my patient with acute decompensated congestive heart failure (ADCHF)?