A 72-year-old woman was admitted to our hospital for esophagectomy for esophageal cancer. On the third postoperative day, she developed polyuria (3.8 L/day), massive natriuresis, hyponatremia (112 mEq/L), hyperkalemia (5.6 mEq/L), and decreased central venous pressure, which was refractory to isotonic saline infusion. Laboratory findings indicated proximal tubular injury (high urinary
Postoperative hyponatremia is usually attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), which results from administration of excessive fluid in the presence of nonosmotic secretion of ADH [
A 72-year-old woman was admitted to our hospital for surgery for esophageal cancer. At admission, her blood pressure was 120/70 mmHg and pulse rate was 76 beats per minute. She was 152 cm in height and weighted 62 Kg. Physical examination was unremarkable. Preoperatively, renal function was moderately decreased (creatinine, 0.95 mg/dL, blood urea nitrogen: 16.5 mg/dL, uric acid: 5.7 mg/dL, sodium: 144 mEq/L, potassium: 4.1 mEq/L, chloride 110 mEq/L, phosphorus 3.7 mg/dL). During the thoracoscopic esophagectomy, blood loss was 460 ml, and hemodynamics were stable.
Postoperatively, approximately 2 L of hypotonic fluid (0.2% saline with 4.3% dextrose) daily were administered, urine volume was stable (1.1–1.8 L), and plasma sodium levels were unchanged (140 mEq/L). However, on the third postoperative day, she suddenly developed polyuria (3.8 L/day) together with a decrease in CVP (Figure
Laboratory data on consultation.
Urinalysis | Biochemistry | Endocrinolgy | |||
Osmolality | 766 mOsm/l | Osmolality | 251 mOsm/l | Cortisol | 30.7 |
Sodium | 166 mEq/L | Sodium | 119 mEq/L | ACTH | 29 pg/ml (7–56) |
Potassium | 52 mEq/L | Potassium | 4.7 mEq/L | Aldosterone | 161 pg/ml |
Chloride | 183 mEq/L | Chloride | 88 mEq/L | PRA | 1.3 ng/ml/h |
9.3 mg/l | Calcium | 8.0 mg/dL | AVP | 9.96 pg/ml | |
( | Phosphorus | 3.2 mg/dL | freeT4 | 1.7 ng/ml (0.9–1.7) | |
NAG | 41.0 IU/l (0.7–11.2) | Creatinine | 0.5 mg/dL | TSH | 1.22 |
TTKG | 3.6 | BUN | 17.8 mg/dL | Cytokines | |
TmP/GFR | 2.4 mg/dL | Uric acid | 1.4 mg/dL | IL- 6 | 34.8 pg/ml ( |
Glucose | 187 mg/dL | TNF- |
NAG: N-acetyl-
Clinical course.
The present case developed hyponatremia on the fourth postoperative day together with increased urine volume, a negative balance for water, an increase in hematocrit values, and decreased CVP. Thus, ECV status was considered hypovolemic, which was not consistency with the diagnosis of a SIADH.
The cause of hypovolemic hyponatremia was thought to be renal loss because urinary sodium concentrations were high. The cause of renal loss includes diuretic use, adrenal insufficiency, osmotic diuresis, cerebral salt wasting syndrome (CSWS), and SLN. Diuretic use, adrenal insufficiency, and osmotic diuresis were ruled out clinically and endocrinologically. CSWS was introduced in 1950 [
We believe that proximal tubular dysfunction existed in the present case. First, urinary concentrations of
We considered that not only proximal tubule but also another segment of renal tubules were affected, because if the proximal tubule is the only affected tubule, more distal tubules can compensate for reduced proximal tubule sodium reabsorption and severe hyponatremia rarely occurs. Final regulation of sodium resbsorption is done at the CCD. The coexistence of hyperkalemia and hyponatremia, although hyperkalemia is an unusual presentation of SLN, led us to suspect that the CCD could not compensate for reduced proximal tubule sodium reabsorption due to refractoriness to aldosterone. Under conditions of maximal aldosterone action, the TTKG should be 7–10. In the present case, however, TTKG was 3.6, suggesting aldosterone action was suppressed.
Because final regulation of free water is done at the medullary collecting duct via the action of ADH, sodium loss itself does not necessarily cause hyponatremia. The final cause of hyponatremia was considered elevated ADH level for her plasma osmolality together with increased urinary sodium loss and intake of free water due to infusion of hypotonic fluid. Causes of nonosmotic secretion of ADH in the present case include ECV depletion and postoperative stress. To suppress ADH secretion, volume load was done with 3% saline infusion, and fludrocrotisone, which acts directly on the CCD, was administrated. The patient responded well to this treatment.
Postoperative hyponatremia occurs despite near-isotonic saline infusion in which hyponatremia is caused by generation of electrolyte-free water during excretion of hypertonic urine; this is referred to as desalination phenomenon [
The driving force for proximal tubule Na reabsorption depends on electrochemical gradients generated by Na/K ATPase at the basolateral membrane. Endothelial derived inflammatory cytokines, mediated by nitric oxide production, reduce proximal tubule Na reabsorption by downregulation of Na/K ATPase activity [
In summary, we encountered a patient who developed severe hyponatremia after esophagectomy for esophageal cancer. The cause of hyponatremia was considered renal tubular dysfunction together with elevated ADH level. Postoperatively, it is important to look for the development of SLN for proper management.