Sustained vasoconstriction associated with daily cyclosporine dose in heart and lung transplant recipients: potential pathophysiologic role of endothelin.
Transient decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) have been associated with each daily dose of cyclosporine (CYA) in patients with renal allografts. We examined the differential dose effects of CYA on native renal function in 24 recipients of heart or lung transplants (treated with 7.3 +/- 0.5 mg/kg/day [mean +/- SEM]) and in seven patients with psoriasis (treated with 4.2 +/- 0.7 mg/kg/day). GFR and RPF were measured by urinary inulin and para-aminohippuric acid clearances 2 hours before the morning CYA dose and for 6 hours after. The age of heart and lung transplant recipients at renal study (2 months after transplantation) was 47 +/- 2.0 years. Their serum creatinine levels rose from 80 +/- 4.0 mumol/L during the first week after transplantation to 120 +/- 4.0 mumol/L at renal study (p < 0.0001). Their GFR and RPF were decreased before the CYA dose at 64 +/- 2.4 and 340 +/- 16 ml/min per 1.73 m2 and did not vary during the study. In comparison, the age of patients with psoriasis was 51 +/- 4.6 years at renal study (24 +/- 4.0 months after CYA treatment). Their serum creatinine levels rose from 80 +/- 4.0 mumol/L before treatment to 100 +/- 10 mumol/L at renal study (p = 0.07). Transient decreases of their baseline GFR and RPF (85 +/- 7.4 and 380 ml/min per 1.73 m2) with a nadir occurring during the first 2 hours of CYA ingestion were observed together with the recovery of these parameters toward baseline by the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Pei
Y
Y
Department of Medicine, Toronto Hospital, Ontario, Canada.
Chan
C
C
Cattran
D
D
Cardella
C
C
Zaltzman
J
J
Lopez
M
M
Tong
J
J
Schachter
R
R
Maurer
J
J
D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction
D016232:Endothelins; D016572:Cyclosporine