Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression

Clin Transplant. 2004 Apr;18(2):186-92. doi: 10.1046/j.1399-0012.2003.00154.x.


Background: After renal transplantation immunosuppressive drugs-like cyclosporin A (CsA) and FK506 induce either hypoaldosteronism or pseudo-hypoaldosteronism presenting with hyperkalemia and metabolic acidosis. We investigated the relationship between renal allograft function under CsA therapy and plasma aldosterone concentration, potassium- and water homeostasis and mineralocorticoid receptor (MR) expression level in peripheral leukocytes.

Methods: We studied 21 renal transplant patients under CsA therapy and 12 healthy controls. Transplant recipients were studied before and under fludrocortisone treatment. Using quantitative reverse-phase polymerase chain reaction (RT-PCR) specific for the MR, we analyzed the level of expression of MR in peripheral leukocytes.

Results: In acidotic transplant recipients (HCO(3) 18.5 +/- 1.2 mM) renal function was only slightly impaired with 2.0 +/- 0.2 mg creatinine/dL when compared with 1.8 +/- 0.3 mg/dL (ns) in non-acidotic patients (HCO(3) 23.0 +/- 2.8 mM). Mean plasma aldosterone levels in renal transplant recipients did not differ from control levels (150 +/- 33 pg/mL vs. 148 +/- 33 pg/mL, ns). In contrast, the expression level of MR in peripheral leukocytes of renal transplant recipients treated with CsA was significantly decreased when compared with healthy controls without renal disease (120 +/- 78 vs. 423 +/- 73 RNA molecules/0.5 microg total RNA, p < 0.01). The level of expression of MR in renal transplant recipients did not differ between acidotic patients and non-acidotic patients (ns). The application of fludrocortisone reversed hyperkalemia and metabolic acidosis without significant effect on MR expression.

Conclusions: The present data demonstrate that hyperkalemia and metabolic acidosis following CsA treatment in kidney transplantation might be associated with a down-regulation of MR expression on peripheral leukocytes. Electrolyte imbalance is reversible on application of fludrocortisone. This observation supports fludrocortisone treatment in transplant patients with severe electrolyte disturbances.

MeSH terms

  • Acidosis / chemically induced
  • Acidosis / drug therapy
  • Acidosis / metabolism
  • Adult
  • Aldosterone / blood*
  • Body Water / metabolism
  • Calcineurin Inhibitors
  • Cyclosporine / adverse effects*
  • Cyclosporine / therapeutic use
  • Down-Regulation
  • Fludrocortisone / therapeutic use
  • Homeostasis
  • Humans
  • Hyperkalemia / chemically induced
  • Hyperkalemia / drug therapy
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Leukocytes / metabolism
  • Middle Aged
  • Potassium / blood
  • Receptors, Mineralocorticoid / metabolism*
  • Renin / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Water-Electrolyte Imbalance / drug therapy
  • Water-Electrolyte Imbalance / etiology


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Receptors, Mineralocorticoid
  • Aldosterone
  • Cyclosporine
  • Renin
  • Potassium
  • Fludrocortisone