Steroid withdrawal after long-term medication for immunosuppressive therapy in renal transplant patients: adrenal response and clinical implications.
BACKGROUND
Withdrawal of steroids should be attempted after organ transplantation because of their adverse cardiovascular and metabolic effects. However, immunological, haemodynamic and symptomatic complications may occur due to the suppression of endogenous corticoid hormone synthesis under exogenous steroid intake. We have examined the effect of chronic steroid medication on adrenocortical function, and of steroid withdrawal, in immunologically stable renal transplant patients.


METHODS
Sixty-three patients under long-term prednisone therapy (mean+/-SD 36+/-47 months) were assessed regarding basal fasting cortisol concentration and adrenocortical stimulation by the low-dose Synacten test both prior to and after stepwise prednisone withdrawal. Renal graft function (determined as the calculated glomerular filtration rate according to the Cockroft-Gault formula), mean arterial blood pressure and clinical status were evaluated concomitantly.


RESULTS
Basal fasting cortisol concentration was clearly suppressed in 14% of patients under long-term steroid medication, and adrenocortical stimulation by the low-dose Synacten test was impaired in 31% after steroid withdrawal. About a third of all patients were symptomatic with fatigue (60%), arthralgias (60%), muscular weakness (20%), loss of appetite (20%), hypotension (15%) or headaches (5%). The incidence of symptoms was much higher in patients with low basal fasting cortisol concentration prior to steroid withdrawal, and after >2 years of steroid medication. Renal graft function, determined as glomerular filtration rate, decreased only slightly overall by approximately 5%, and was more pronounced in symptomatic vs asymptomatic patients (-7 vs -2 ml/min, respectively), as was the fall in mean arterial pressure (-10 vs -4.2 mmHg, respectively).


CONCLUSIONS
Adrenal function is impaired in renal transplant patients receiving long-term steroid medication as part of their immunosuppressive regimen. This may lead to mainly symptomatic complications when steroids are withdrawn. The slight decrease in glomerular filtration rate probably can be ascribed mostly to the effect of steroids on systemic renal haemodynamics. It is recommended to consider cessation of steroid medication within 48 months of therapy, and after determination of basal cortisol to identify patients with potential complications.
Renal Division, Department of Medicine, University Hospital, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Marco
M
Miozzari
Patrice M
PM
Ambühl
D000311:Adrenal Glands / Q000187:drug effects* / Q000503:physiopathology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D015331:Cohort Studies; D003366:Cosyntropin; D004334:Drug Administration Schedule; D005215:Fasting / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D012079:Renal Circulation / Q000187:drug effects
D007166:Immunosuppressive Agents; D003366:Cosyntropin; D011241:Prednisone; D006854:Hydrocortisone