title: 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.affiliation: Department of Medicine III, Solingen General Hospital, University of Cologne, Solingen, Germany. heering@klinikumsolingen.de
authors.forename: P J
authors.initials: PJ
authors.lastname: Heering
authors.forename: C
authors.initials: C
authors.lastname: Kurschat
authors.forename: D T
authors.initials: DT
authors.lastname: Vo
authors.forename: N
authors.initials: N
authors.lastname: Klein-Vehne
authors.forename: K
authors.initials: K
authors.lastname: Fehsel
authors.forename: K
authors.initials: K
authors.lastname: Ivens
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D001834:Body Water / Q000378:metabolism; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D015536:Down-Regulation; D005438:Fludrocortisone / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016030:Kidney Transplantation; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012083:Renin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy / Q000209:etiology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D016572:Cyclosporine; D012083:Renin; D011188:Potassium; D005438:Fludrocortisone