Case Presentation: Case 1: A 56 year old female with history of metastatic adenocarcinoma of lung on cycle 1 day 8 of carboplatin/permetrexed/pembrolizumab therapy presented with fever, headache and altered mental status. She was diagnosed with Methicillin resistant Staphylococcus aureus (MRSA) bacteremia and was treated with antibiotics. She presented with potassium levels of 3.4 mmol/l (ref range 3.5 -5.1 mmol/l) which dropped to a minimum of 2.6 mmol/l despite 60-120 meq potassium chloride replacement per day. Magnesium was 1.3 mg/dl (ref range 1.6-2.6 mg/dl) despite 4-6 gm of Magnesium replacement per day. Arterial blood gas showed pH of 7.67 (ref range 7.35-7.45), pCO2 of 33.7 mm Hg (ref range: 35-45 mm Hg) and Bicarbonate of 38 mmol/l (ref range: 21-28 mmol/l) with trans-tubular potassium gradient of 6.41 suggestive of renal losses. She was diagnosed with Carboplatin induced tubular damage and was started on multiple doses of daily potassium chloride replacements, daily magnesium replacement, and amiloride 5 mg daily with improvement in her potassium and magnesium levels. On follow up she continues to take these medications.
Case 2: A 43 year old male with no significant history presented with headache, fever and altered mental status. He was diagnosed with HIV and cryptococcal meningitis and was started on liposomal amphotericin B and fluconazole. On presentation potassium levels were 3.3 mmol/l which normalized next day with replacement but started to fall and dropped to a nadir of 2.5 mmol/l at day 5 of therapy despite 60-80 meq potassium chloride replacement per day. Magnesium was 1.9 mg/dl and arterial blood gas showed pH of 7.52, pCO2 of 29 mm Hg and Bicarbonate of 24 mmol/l with trans-tubular potassium gradient of 11.23 suggestive of renal losses. He was diagnosed with amphotericin B induced tubular damage and was started on multiple daily potassium chloride replacements during the course of Amphotericin B therapy and his levels stabalized without amiloride therapy. Eventually after cessation of therapy, he did not require any potassium supplementation.

Discussion: Electrolyte imbalance especially hypokalemia is common in hospitalized patients and usually respond to replacement therapies, but persistent hypokalemia despite adequate replacement is rare. Trans-tubular potassium gradient is an easy way to differentiate between renal vs non-renal causes of potassium wasting and is thus helpful in such cases of resistant hypokalemia.

Drugs should be considered as possible causes of chronic unexplained electrolyte disorders. Cisplatin and other platinum based drugs have been associated with hypokalemic metabolic alkalosis with hypomagnesemia due to tubular toxicity and can mimic barter-gitelman syndrome. Similarly, Amphotericin B may induce various grades of tubule-toxic effects leading to persistent hypokalemia. Optimal and aggressive potassium replacement is required but some patients may require addition of epithelial sodium channel blockers.

Conclusions: Drugs should be identified as iatrogenic causes of hypokalemia and early recognition and optimal replacement are the corner stones of treatment. Where some of these effects can be temporary, some can lead to permanent potassium wasting and lifelong supplementation may be required.