Introduction:
One of the most widely used immunosuppressive medications is tacrolimus, yet there is little evidence that tacrolimus-induced severe symptomatic hyponatremia affects kidney transplant recipients.1-4 In the present study, we report a case of tacrolimus-induced hyponatremia in a living donor kidney recipient, in whom tacrolimus-induced salt-losing nephropathy was corrected with fludrocortisone addition, and all other possible causes of hyponatremia were ruled out.
Methods:
A 31-year-old male patient who received kidney transplantation in Nov 2022 from his father with stable graft function of creatinine ~ 1.5 to 1.7 mg/dl. September 2023 came with complaints of anorexia, nausea, vomiting, and headache. He had a serum creatinine level of 1.7 mg/dL. He was found to have severe hyponatremia with a serum sodium of 120 mmol/L and a hypokalaemia of 2.6 mmol/L. He was receiving bisoprolol 2.5 mg per day for hypertensive treatment and triple immunosuppressive regimen of tacrolimus 3 mg/day, mycophenolate sodium 1440 mg/day, and prednisolone 5 mg/day. His tacrolimus level was 7.26 ng/ml. In thyroid function tests, serum osmolality was in the normal range, and this was his very first hyponatraemic state after the successful kidney transplantation. He was not receiving any drugs that might result hyponatremia, such as diuretics or parenteral fluids. His blood glucose level was 95 mg/dL, and he had no sign of osmotic diuresis. He received 3% hypertonic NaCl along with salt, potassium supplementation, serum sodium level improved to 132 mmol/L after 72 hours. One month later he came with c/o severe weakness and giddiness. On evaluation serum sodium 112 mmol/L with serum potassium 3.1 mmol/L, tacrolimus level was 6.43 ng/ml. We suspected tacrolimus to be responsible for the salt-losing state. His serum osmolarity 278, urine osmolarity 199, spot sodium excretion 79 mmol/L with 24 hr sodium excretion of 319 mmol/day. Recipient opted for fludrocortisone therapy and he was started with fludrocortisone 200 mcg/day. After 1 week, his serum sodium level improved to 136 mmol/dL with normal potassium and stable graft function with no need of more hypertonic fluid replacement. Repeated 24-hour sodium excretion was 149 mmol/day. All the symptoms due to hyponatremia were resolved. We slowly tapered off fludrocortisone. During 2 months of follow-up the serum sodium levels of our patient remained in the normal range, which showed that the delayed effect of hypertonic saline and volume contraction was not responsible for resolving of the hyponatraemic state.
Results:
Few studies have documented a tacrolimus-induced salt losing nephropathy following solid organ transplantation. Higgins et al.'s research revealed that tacrolimus users were more likely to experience hyponatremia than cyclosporine users. The median time following transplantation for the patients who experienced hyponatremia was 18 days, and tacrolimus was the only reason identified. In our instance, the tacrolimus level was within the desired range (7.26 ng/mL) when the patient experienced tacrolimus-induced symptomatic hyponatremia > 10 months following transplantation. A urine production of 1.5 to 2.8 L/day in our patient rules out hyponatremia based on posttransplant polyuria. Exclusion of additional potentially concerning conditions included hyperglycaemia, hypothyroidism, diuretic use, parenteral hypotonic fluid injection, and any medication other than tacrolimus that could potentially result in hyponatremia1–5.
It has been proposed that tacrolimus affects the distal tubular Na-K-2Cl cotransporter, which could lead to an aldosterone-resistant salt-losing nephropathy. Consequently, it was discovered that tacrolimus-induced nephropathy responded well to fludrocortisone.
Conclusions:
Even at target dosages of tacrolimus, calcineurin inhibitor toxicity and tubular dysfunction can occur. Therefore, resistance symptomatic hyponatremia in a transplant patient on tacrolimus needs to be considered while making a differential diagnosis of severe hyponatremia. When tacrolimus causes hyponatremia, fludrocortisone can be used who experience a salt-losing state.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.