Calcineurin inhibitor‐induced hyperkalemia and salt‐sensitive hypertension in Early Post‐Kidney Transplant Period
Authors: Tantisattamo Ekamol , Chokechanachaisakul Attasit , Pitukweerakul Siwadon , Ratanasrimetha Praveen , Shrivastava Pritika , Samarapungavan Dilip 
Published: November 2023

Background

Calcineurin inhibitor (CNI) is the cornerstone of maintenance immunosuppression in kidney transplantation. However, it could lead to several fluid and electrolyte disturbances including salt‐sensitive hypertension and hyperkalemia. Hyperkalemia could be treated with aldosterone agonist; however, this treatment is limited by salt and water retention and uncontrolled hypertension (HTN). We report a case of kidney transplant recipient with persistent posttransplant hyperkalemia, which was resolved with aldosterone agonist.

Case description

A 65‐year‐old Caucasian man with a past medical history significant for end‐stage renal disease secondary to type 2 diabetes mellitus (T2DM) underwent an uneventful deceased donor renal transplantation with basiliximab induction. Maintenance immunosuppression included tacrolimus, mycophenolate mofetil, and prednisone. Prophylaxis trimethoprim/sulfamethoxazole (TMP/SMZ) was initiated. Tacrolimus was started on postoperative day 1 and was titrated to maintain the 12‐hour tacrolimus trough level of 8 ng/mL. Postoperative course was complicated by persistent hyperkalemia with serum potassium of 5.1 – 5.7 mmol/L and non‐anion gap metabolic acidosis with serum bicarbonate down to 18 mmol/L. He also developed uncontrolled hypertension with average systolic and diastolic blood pressure (BP) of 180 and 60 mmHg, respectively (Figure 1). On the posttransplant day 11, serum potassium increased up to 6.4 mmol/L even though his urine output ranged from 1.6 to 2.2 L/day and serum creatinine had trended down to 2.34 mg/dL from the pretransplant serum creatinine of 10.31 mg/dL. In addition to low potassium diet, he was treated with sodium polystyrene sulfonate with several bowel movements; however, serum potassium still elevated. Therefore, fludrocortisone was started and serum potassium was normalized. BP remained high and doseing of antihypertensive medication were adjusted.

Discussion

Tacrolimus leads to hyperkalemia from inhibiting basolateral Na‐K ATPase at the collecting duct causing impaired transepithelial potassium secretion from decreased sodium uptake. Our patient had new‐onset hyperkalemic non‐anion gap metabolic acidosis since early post‐kidney transplant period even with improving renal allograft function and good urine output. Tacrolimus causing distal tubular defect mimicking type 4 renal tubular acidosis (T4RTA) that was corrected by aldosterone agonist. Even though diabetes is one of the most common causes of T4RTA, the new renal allograft should not be affected by the underlying T2DM in such a short posttransplant period. TMP/SMX could contribute to hyperkalemia. Tacrolimus also causes hypertension from renal afferent arteriolar vasoconstriction and activation of Na‐Cl cotransporter (NCC) in the distal collecting tubule (DCT) and subsequently salt‐sensitive hypertension.

Conclusions

Aldosterone agonist could treat tacrolimus‐induced hyperkalemia from distal tubular injury; however, hypertension from salt and fluid retention limits this therapy. Since tacrolimus stimulates NCC, thiazide diuretics could potentially be used for BP control once renal allograft function is stable. Both low dietary potassium and sodium intakes should be part of therapeutic strategies to control serum potassium and HTN.