Renal salt wasting without cerebral disease: Diagnostic value of urate determinations in hyponatremia

CASE PRESENTATION A 76-year-old woman, who sustained an accidental fracture of the femoral neck, developed hyponatremia after admission. The diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was made by the consulting internist and fluid restriction of 700 cc/day was instituted. Her serum sodium (Na) fluctuated between 122 and 129mmol/l and a renal consultation was requested on the eighth day after undergoing a hemiarthroplasty of the hip when she was ambulating and on no pain medication. Her blood pressure was 100/60 mm Hg, pulse 92 beats/min and there was poor tissue turgor, flat jugular veins, and dry mucous membranes. There was no edema, third spacing, postural hypotension or neurological abnormalities. Her medications included docusate sodium, milk of magnesia, simvastatin, and warfarin. She was not on drugs such as atorvastatin, fenofibrate, or losartan which reduce serum urate by increasing renal urate excretion. 1-3 A low baseline urine Na (UNa) concentration of 6 mmol/l suggested a hypovolemic condition with normal renal function 4 that should result in a prerenal state characterized by low UNa, azotemia, and hyperuricemia. The baseline serum urate of 3.4 mg/dl, however, was inconsistent with prerenal azotemia and its coexistence with hyponatremia was suggestive of SIADH or renal salt wasting. 4-6 The patient was, therefore, included in an IRB-approved protocol to differentiate SIADH from renal salt wasting. After obtaining an informed consent, a blood volume study was performed, using a radioisotope dilution technique.7 With a hematocrit of 31%, the red cell volume was decreased by 28% and the plasma volume increased by 4.7%, resulting in a net blood volume reduction of 7.1%. The pertinent baseline laboratory data are summarized in Table 1. The baseline plasma renin, aldosterone, antidiuretic hormone (ADH), and fractional urate excretion were elevated at 8.63ng/ml/h, 16.5ng/dl, 2.5pg/ml, and 29.6% (normal 5-10%), respectively. Plasma osmolality was decreased at 260 mosm/kgH 2 O, atrial natriuretic peptide was in the low normal range at 35 pg/ml, serum phosphorus and urate were decreased at 2.4 and 3.4 mg/dl, respectively. Renal, adrenal, and thyroid functions were normal. The chest X-ray and urinalysis were normal. Saline was then infused at 125 ml/h for 48 h. Urine osmolality of all spontaneously voided urine was immediately determined and when her urine osmolality decreased to 152 mosM/kgH 2 O at 13.3h, a repeat plasma ADH was undetectable when the serum osmolality was 268 mosm/kgH 2 O. At this time, she had received 1660 ml of saline overnight and excreted 955 ml of urine. The plasma renin and aldosterone decreased to 2.95 ng/ml/h and 7.6ng/dl, respectively, and plasma atrial natriuretic peptide increased to a high normal 65 pg/ml. The serum Na remained unchanged at 129mmol/l but the serum urate decreased from 3.4 to 1.7 mg/dl. It should be noted that the baseline urine osmolality of 321 mosm/kgH 2 O increased to 587 mosm/kgH 2 O and the UNa only increased from a baseline of 6 to 18 mmol/l in the first urine passed 4 h after initiation of saline infusion (Figure 1, Table 2). The serum Na gradually increased from 129 to 138 mmol/l at 45.8 h (Figure 2), as serum urate decreased to 1.0 mg/dl and fractional urate excretion remained elevated (Figure 2). Her UNa increased to a peak of 82 mmol/l at 8.1 h (Table 2).