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

Abstract

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.

• Authors: P J Heering, C Kurschat, D T Vo, N Klein-Vehne, K Fehsel, K Ivens
• Journal: Clinical transplantation (Clin Transplant) Vol. 18 Issue 2 Pg. 186-92 (Apr 2004) ISSN: 0902-0063 [Print] Denmark
• PMID: 15016134 (Publication Type: Journal Article)

Chemical References

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

Topics

• Acidosis (chemically induced, drug therapy, metabolism)
• Adult
• Aldosterone (blood)
• Body Water (metabolism)
• Calcineurin Inhibitors
• Cyclosporine (adverse effects, therapeutic use)
• Down-Regulation
• Fludrocortisone (therapeutic use)
• Homeostasis
• Humans
• Hyperkalemia (chemically induced, drug therapy)
• Immunosuppressive Agents (adverse effects, 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, etiology)