Clinical Investigation

Kidney International (1994) 46, 1216–1222; doi:10.1038/ki.1994.387

A prospective study of renal structure and function in psoriasis patients treated with cyclosporin

Eric W Young, Charles N Ellis, Joseph M Messana, Kent J Johnson, Alan B Leichtman, Michael J Mihatsch, Ted A Hamilton, Daniel S Groisser, Mark S Fradin and John J Voorhees

Division of Nephrology, Department of Internal Medicine, The Dermatopharmacology Unit, Department of Dermatology, and the Department of Pathology, University of Michigan Medical School, and the Veterans Affairs Medical Center, Ann Arbor, Michigan, USA; The Institute for Pathology, University of Basel, Basel, Switzerland

Correspondence: John J Voorhees MD, Department of Dermatology, University of Michigan, 1910 Taubman Center, Ann Arbor, Michigan 48109-0314, USA.

Received 7 February 1994; Revised 25 April 1994; Accepted 25 April 1994.

Top

Abstract

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 plusminus 0.2 vs. 0.3 plusminus 0.1, P < 0.0001) and tubular atrophy (1.6 plusminus 0.2 vs. 0.3 plusminus 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 plusminus 0.2 to 2.4 plusminus 0.3, P = 0.002) and tubular atrophy (1.4 plusminus 0.2 to 1.9 plusminus 0.2, P = 0.053), and the onset of cyclosporin-associated arteriolopathy (0 to 0.5 plusminus 0.2, P = 0.02). Quantitative digital morphometric analysis of trichrome-stained specimens also showed increased interstitial fibrosis (22.5 plusminus 1.5 to 32.0 plusminus 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.

Top

References

  1. Kahan BD: Cyclosporine. N Engl J Med 321:1725–1738, 1989 | PubMed | ISI | ChemPort |
  2. Ellis CN, Fradin MS, Messana JM, Brown MD, Siegel MT, Hartley AH, Rocher LL, Wheeler S, Hamilton TA, Parish TG, Ellis-Madu M, Duell E, Annesley TM, Cooper KD, Voorhees JJ: Cyclosporine for plaque-type psoriasis: Results of a multidose, double-blind trial. N Engl J Med 324:277–284, 1991 | PubMed | ISI | ChemPort |
  3. Mihatsch MJ, Thiel G, Ryffel B: Histopathology of cyclosporine nephrotoxicity. Transplant Proc 20(Suppl 3):759–771, 1988 | PubMed | ChemPort |
  4. Mihatsch MJ, Thiel G, Basler V, Ryffel B, Landmann J, von Overbeck J, Zollinger HU: Morphological patterns in cyclosporine-treated renal transplant recipients. Transplant Proc 17:101–116, 1985
  5. Austin HA III, Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Klippel JH, Decker JL, Balow JE: Prognostic factors in lupus nephritis: Contribution of renal histologic data. Am J Med 75:382–391, 1983 | Article | PubMed | ISI |
  6. International Kidney Biopsy Registry of Cyclosporin A (Sandimmun) in Autoimmune Diseases: Kidney biopsies in control or cyclosporin A-treated psoriatic patients. Br J Dermatol 122(Suppl 36):95–100, 1990
  7. Israelit AH, Long DL, White MG, Hull AR: Measurement of glomerular filtration rate utilizing a single subcutaneous injection of 125I-iothalamate. Kidney Int 4:346–349, 1973 | PubMed | ISI | ChemPort |
  8. Bolton S: Pharmaceutical Statistics: Practical and Clinical Applications (2nd ed), New York, Marcel Decker, Inc., 1990, p. 494
  9. Annesley T, Matz K, Clayton L, Giacherio D: Liquid-chromato-graphic analysis for cyclosporine with use of a microbore column and small sample volume. Clin Chem 32:1407–1409, 1986 | PubMed | ChemPort |
  10. Myers BD, Ross J, Newton L, Luetscher J, Perlroth M: Cyclos-porine-associated chronic nephropathy. N Engl J Med 311:699–704, 1984 | PubMed | ISI | ChemPort |
  11. Svenson K, Bohman S-O, Hällgren R: Renal interstitial fibrosis and vascular changes: Occurrence in patients with autoimmune diseases treated with cyclosporin. Arch Intern Med 146:2007–2010, 1986
  12. Palestine AG, Austin HA, Balow JE, Antonovych TT, Sabnis SG, Preuss HG, Nussenblatt RB: Renal histopathologic alterations in patients treated with cyclosporine for uveitis. N Engl J Med 314:1293–1298, 1986 | PubMed | ISI | ChemPort |
  13. Deray G, Benhimida M, Le Hoang P, Maksud P, Aupetit B, Bamelou A, Jacobs C: Renal function and blood pressure in patients receiving long-term, low-dose cyclosporine therapy for idiopathic autoimmune uveitis. Ann Intern Med 117:578–583, 1992
  14. Greenberg A, Egel JW, Thompson ME, Hardesty RL, Griffith BP, Bahnson HT, Bernstein RL, Hastillo A, Hess ML, Puschett JB: Early and late forms of cyclosporine nephrotoxicity: Studies in cardiac transplant recipients. Am J Kidney Dis 9:12–22, 1987
  15. Zachariae H, Hansen HE, Kragballe K, Olsen S: Morphologic renal changes during cyclosporine treatment of psoriasis. J Am Acad Dermatol 26:415–419, 1992 | PubMed |
  16. Lindeman RD, Tobin JD, Shock NW: Association between blood pressure and the rate of decline in renal function with age. Kidney Int 26:861–868, 1984 | PubMed | ISI | ChemPort |
  17. Walker WG, Neaton JD, Cutler JA, Neuwirth R, Cohen JD: Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. JAMA 268:3085–3091, 1992 | Article | PubMed | ISI | ChemPort |
  18. Powles AV, Cook T, Hulme B, Baker BS, Lewis HM, Thomas E, Valdimarsson H, Fry L: Renal function and biopsy findings after 5 years' treatment with low-dose cyclosporin for psoriasis. Br J Dermatol 128:159–165, 1993 | PubMed | ISI | ChemPort |
  19. Feutren G, Mihatsch MJ: Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. N Engl J Med 326:1654–1660, 1992 | PubMed | ISI | ChemPort |
  20. Gilbert SC, Emmett M, Menter A, Silverman A, Klintmalm G: Cyclosporine therapy for psoriasis: Serum creatinine measurements are an unreliable predictor of decreased renal function. J Am Acad Dermatol 21:470–474, 1989
  21. Powles AV, Carmichael D, Hulme B, Thomas E, McFadden J, Baker B, Valdimarsson H, Fry L: Renal function after long-term low-dose cyclosporin for psoriasis. Br J Dermatol 122:665–669, 1990
  22. Korstanje MJ, Bilo HJG, Stoof TJ: Sustained renal function loss in psoriasis patients after withdrawal of low-dose therapy. Br J Dermatol 127:501–504, 1992
  23. Margolis DJ, Guzzo C, Johnson J, Lazarus GS: Alterations in renal function in psoriasis patients treated with cyclosporine, 5 mg/kg/day. J Am Acad Dermatol 195–197, 1992
  24. Elzinga LW, Roseb S, Bennett WM: Dissociation of glomerular filtration rate from tubulinterstitial fibrosis in experimental chronic cyclosporine nephropathy: Role of sodium intake. J Am Soc Nephrol 4:214–221, 1993 | PubMed | ISI | ChemPort |
  25. Schainuck LI, Striker GE, Cutler RE, Benditt EP: Structural-functional correlations in renal disease. II. The correlations. Hum Pathol 1:631–641, 1970 | Article | PubMed | ChemPort |

Extra navigation

.
ADVERTISEMENT