A prospective study of renal structure and function in psoriasis patients treated with cyclosporin.
The impact of long-term cyclosporin therapy on kidney structure and function was evaluated in psoriasis patients with normal baseline renal function. Patients received cyclosporin at an average dose 3.9 mg/kg/day for up to three years and underwent serial kidney biopsies and measurements of iothalamate clearance and serum creatinine concentration. Kidney biopsy specimens (assessed on a scale of 0 to 4 where 0 = normal and 4 = severe) from 19 cyclosporin-treated patients as compared to 38 age-matched transplant donors showed increased interstitial fibrosis (1.9 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) and tubular atrophy (1.6 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) at one year. Eleven patients had a second biopsy after an additional two years of cyclosporin treatment demonstrating additional interstitial fibrosis (1.8 +/- 0.2 to 2.4 +/- 0.3, P = 0.002) and tubular atrophy (1.4 +/- 0.2 to 1.9 +/- 0.2, P = 0.053), and the onset of cyclosporin-associated arteriolopathy (0 to 0.5 +/- 0.2, P = 0.02). Quantitative digital morphometric analysis of trichrome-stained specimens also showed increased interstitial fibrosis (22.5 +/- 1.5 to 32.0 +/- 2.0% of interstitial area, P = 0.0008). Iothalamate clearance declined at an average rate of -3.1 ml/min/1.73 m2 per year (95% CI -5.8, -0.3) during the period of cyclosporin treatment. The slope of reciprocal serum creatinine declined by -0.06 dl/mg per year (95% CI -0.08, -0.04). Chronic cyclosporin treatment of otherwise healthy psoriasis patients is associated with progressive renal structural injury and reduced glomerular filtration rate.
Young
E W
EW
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
Ellis
C N
CN
Messana
J M
JM
Johnson
K J
KJ
Leichtman
A B
AB
Mihatsch
M J
MJ
Hamilton
T A
TA
Groisser
D S
DS
Fradin
M S
MS
Voorhees
J J
JJ
D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007483:Iothalamic Acid / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D007483:Iothalamic Acid; D016572:Cyclosporine; D003404:Creatinine