From the Guidelines
When differentiating between SIADH and hypovolemic hyponatremia, serum uric acid and FE uric acid are crucial diagnostic tools, with SIADH typically presenting with low serum uric acid and high FE uric acid, and hypovolemic hyponatremia presenting with normal to high serum uric acid and low FE uric acid. In clinical practice, the distinction between these two conditions is vital due to their different management strategies. According to 1, SIADH is characterized by euvolemic hypoosmolar hyponatremia, with inappropriately high urine osmolality and urinary sodium concentration, and low serum osmolality. Key laboratory findings in SIADH include urine osmolality of > 300 mosm/kg, urinary sodium level of > 40 mEq/L, serum osmolality of < 275 mosm/kg, and serum uric acid concentration of < 4 mg/dL, as noted in 1. The use of serum uric acid and FE uric acid can help in the differential diagnosis, especially when the clinical assessment of volume status is uncertain. For instance, in hypovolemic hyponatremia, the body's attempt to retain sodium and water leads to increased uric acid reabsorption, resulting in higher serum uric acid levels and lower FE uric acid, typically <10% 1. Conversely, SIADH is associated with increased uric acid excretion due to the effect of ADH, leading to lower serum uric acid levels and higher FE uric acid, usually >10%. Understanding these patterns is essential for accurate diagnosis and appropriate management of hyponatremia, as the treatment strategies for SIADH and hypovolemic hyponatremia differ significantly, with SIADH often requiring fluid restriction and potentially vasopressin 2 receptor antagonists, as recommended in 1.
From the Research
Differentiating Between SIADH and Hypovolemic Hyponatremia
- Serum uric acid and fractional excretion (FE) of uric acid can be helpful in differentiating between the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and hypovolemic hyponatremia 2, 3, 4.
- In SIADH, uric acid levels are often low, while in hypovolemic hyponatremia, uric acid levels are often normal to high due to the body's attempt to retain both sodium and uric acid in true volume depletion 2.
- FE uric acid is also a useful marker, with a low FE uric acid (<10%) indicating hypovolemic hyponatremia and a high FE uric acid indicating SIADH 2, 4.
Clinical Use of Uric Acid and FE Uric Acid
- The assessment of uric acid and FE uric acid can be used in conjunction with other laboratory measurements, such as urine sodium and osmolality, to aid in the diagnosis of SIADH and hypovolemic hyponatremia 2, 3.
- A study found that FE uric acid had a high diagnostic accuracy in differentiating between SIADH and non-SIADH patients, with a positive predictive value of 100% if a cutoff value of 12% was used 2.
- Another study suggested a simple diagnostic algorithm based on the assessment of the degree of hyponatremia, urinary osmolality, and FE uric acid to differentiate between SIADH and cerebral/renal salt wasting syndrome in children over 1 year of life 3.
Effect of Hyponatremia Chronicity on Uric Acid Excretion
- Chronicity of hyponatremia may contribute to the high urate clearance observed in SIADH, as evidenced by a study that found that hyponatremia by itself could influence the FE of uric acid 5.
- The study also found that the high FE of uric acid in SIADH patients inversely correlated with glomerular filtration rate only during the hyponatremic state 5.
Role of FE Uric Acid in Diuretic-Induced Hyponatremia
- FE uric acid can be a useful marker in differentiating between SIADH and diuretic-induced hyponatremia, particularly in patients treated with furosemide and/or potassium canrenoate 4.
- However, FE uric acid was found to be a poor marker in discriminating between SIADH and thiazide-induced hyponatremia, highlighting the need for diuretic withdrawal and further evaluation in these patients 4.