Cisplatin-Induced Acute Kidney Injury and Renal Salt Wasting Syndrome

Patients with drug-induced AIN commonly present with signs and symptoms of an allergic-type reaction, including fever, rash, hematuria, pyuria, and costovertebral angle tenderness. The patient lacked these symptoms. However, cisplatin is known to cause ATN in up to 20-30% of patients.⁷ Therefore, despite the lack of the classic muddy-brown, granular casts on urine microscopy, cisplatin-induced ATN remained the most likely etiology of his AKI. Moreover, ATN can cause hyponatremia. ATN is characterized by 3 phases: initiation, maintenance, and recovery phases.⁸ Hyponatremia occurs during the recovery phase, typically starting weeks after renal insult and associated with high urine output and diuresis. This patient presented 1 week after injury and had persistent oliguria, making ATN an unlikely culprit of his hyponatremia.

Our patient presented with hypotonic hyponatremia with a 131 mmol/L initial sodium level and an < 280 mOsm/kg effective serum osmolality, or serum tonicity. The serum tonicity is equivalent to the difference between the measured serum osmolality and the BUN. In the setting of profound AKI, this adjustment is essential for correctly categorizing a patient’s hyponatremia as hyper-, iso-, or hypotonic. The differential diagnosis for this patient’s hypotonic hyponatremia included dilutional effects of hypervolemia, SIADH, hyperthyroidism, adrenal insufficiency, and RSWS. The patient’s volume examination, lack of predisposing comorbidities or suggestive biomarkers, and > 20 mmol/L urinary sodium made hypervolemia unlikely. His urinary osmolality and specific gravity made primary polydipsia unlikely. We worked up his hyponatremia according to a diagnostic algorithm (eAppendix available at doi:10.12788/fp.0198).

The patient had a 217 mOsm/kg serum tonicity and a 270.5 mOsm/kg urine osmolality, consistent with impaired water excretion. His presentation, TSH, and concordant decrease in sodium and potassium made an endocrine etiology of his hyponatremia less likely. In hindsight, a serum cortisol would have been beneficial to more completely exclude adrenal insufficiency. His urine sodium was elevated at 45 mmol/L, raising concern for RSWS or SIADH. The FE_urate helped to distinguish between SIADH and RSWS. While FE_urate is often elevated in both SIADH and RSWS initially, the FE_urate normalizes in SIADH with normalization of the serum sodium. The ideal cutoff for posthyponatremia correction FE_urate is debated; however, a FE_urate value after sodium correction < 11% suggests SIADH while a value > 11% suggests RSWS.⁹ Our patient’s FE_urate following the sodium correction (serum sodium 134 mmol/L) was 21.9%, most suggestive of RSWS.

Treatment

Upon admission, initial treatment focused on resolving the patient’s AKI. The oncology team discontinued the cisplatin-based chemotherapy. His medication dosages were adjusted for his renal function and additional nephrotoxins avoided. In consultation, the nephrology service recommended 100 mL/h fluid resuscitation. After the patient received 3 L of 0.9% sodium chloride, his creatinine showed limited improvement and his sodium worsened, trending from 131 mmol/L to a nadir of 125 mmol/L. We initiated oral free-water restriction while continuing IV infusion of 0.9% sodium chloride at 125 mL/h.

We further augmented his sodium intake with 1-g sodium chloride tablets with each meal. By hospital day 6, the patient’s serum sodium, BUN, and creatinine improved to 130 mEq/L, 50 mg/dL, and 7.7 mg/dL, respectively. We then discontinued the oral sodium chloride tablets, fluid restriction, and IV fluids in a stepwise fashion prior to discharge. At discharge, the patient’s serum sodium was 136 mEq/L and creatinine, 4.8 mg/dL. The patient’s clinical course was complicated by symptomatic hypertension with systolic blood pressures about 180 mm Hg, requiring intermittent IV hydralazine, which was transitioned to daily nifedipine. Concerned that fluid resuscitation contributed to his hypertension, the patient also received several doses of furosemide. At time of discharge, the patient remained hypertensive and was discharged with nifedipine 90 mg daily.

Outcome and Follow-up

The patient has remained stable clinically since discharge. One week after discharge, his serum sodium and creatinine were 138 mmol/L and 3.8 mg/dL, respectively. More than 1 month after discharge, his sodium remains in the reference range and his creatinine was stable at about 3.5 mg/dL. He continues to follow-up with nephrology, oncology, and radiation oncology. He has restarted chemotherapy with a carboplatin-based regimen without recurrence of hyponatremia or AKI. His blood pressure has gradually improved to the point where he no longer requires nifedipine.