Recovery of chronic renal impairment with sirolimus after lung transplantation.
BACKGROUND
Standard immunosuppression after lung transplantation includes calcineurin inhibitors, azathioprine, and steroids. Calcineurin inhibitor administration is associated with an increased renal impairment. Sirolimus shows no renal toxicity and could be used in selected patients.


METHODS
We have prospectively administered sirolimus as an alternative to calcineurin inhibitors in 15 lung transplantation recipients with persistent drug nephrotoxicity. Eight patients had also bronchiolitis obliterans syndrome. The mean serum creatinine and azotemia were 2.7 +/- 1.1 mg/dL and 111 +/- 39 mg/dL. After starting sirolimus, azathioprine was reduced to 50%-25% of baseline, calcineurin inhibitors were gradually reduced and eventually stopped, and steroids were maintained stable. Patients started sirolimus with 2 to 5 mg/d orally; adjustments were made according to trough levels (4 to 12 ng/mL for combined sirolimus + calcineurin inhibitors; 12 to 20 ng/mL as monotherapy), toxicity, and perceived efficacy. Patients were monitored for renal and graft function and clinical status.


RESULTS
A significant creatinine decrease was observed after 6 months of treatment (p < 0.02); azotemia decreased after 1 month and remained stable (p < 0.01). Pulmonary function tests did not show any significant modification from before sirolimus baseline in patients without bronchiolitis obliterans syndrome. There were eight infectious complications and 10 episodes of toxicity (4 dermatitis, 2 epistaxis, 1 headache, 1 diarrhea, 1 nausea, 1 laryngeal cancer). Moderate leukocytopenia (n = 3) and hypertriglyceridemia (n = 6) responded to dose reduction. One patient was lost to follow-up. Three patients died of complications related to bronchiolitis obliterans. One patient underwent transplantation again.


CONCLUSIONS
Sirolimus administration allows amelioration of renal function with a relatively low morbidity and is useful for chronic renal impairment rescue after lung transplantation.
Venuta
Federico
F
Department of Thoracic Surgery, University of Rome La Sapienza, Policlinico Umberto I, Rome, Italy. sofed@libero.it
De Giacomo
Tiziano
T
Rendina
Erino A
EA
Quattrucci
Serena
S
Mercadante
Edoardo
E
Cimino
Giuseppe
G
Ibrahim
Moshen
M
Diso
Daniele
D
Bachetoni
Alessandra
A
Coloni
Giorgio F
GF
D000328:Adult; D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000150:complications; D008171:Lung Diseases / Q000150:complications / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus