• Tacrolimus;
  • Cyclosporine;
  • Neoral;
  • Survival;
  • Rejection;
  • Clinical outcome


  1. Top of page
  2. Abstract
  3. References

Abstract Tacrolimus has proven to be superior to cyclosporine-Sandim-mune with regard to the prevention of acute rejections, but data comparing tacrolimus with Neoral are scarce. A total of 128 consecutive renal transplant recipients was studied. The patients were treated with Neoral-based (n= 74) or tacrolimus-based (n= 54) immuno-suppressive regimens. Survival analyses (Cox regression analysis) were performed on an intention-to-treat basis. Renal function and cardiovascular risk profile were analyzed by means of a repeated-measures analysis of variance (ANOVA) up to 12 months after transplantation. Immunological features were less favorable in the tacrolimus group. Two-year patient and graft survival were comparable. Acute-rejection-free survival was 82% in the tacrolimus group versus 40% in the Neoral group (p < 0.0001). The severity of the rejections (1997 Banff classification) was comparable (P= 0.43). Immunological graft loss (3.7% vs 12.2%, P= 0.02) and conversion because of rejection (0% vs 28.4%, p < 0.001) were less in the tacrolimus group. A higher proportion (68.5% vs 14.9%, p < 0.001) was successfully put on monotherapy. Creatinine clearance, proteinuria, and fractional uric acid clearance were similar. In the tacrolimus group mean blood pressure was comparable, but patients needed less antihypertensive drugs (p < 0.001) and, even with fewer patients on lipidlowering drugs, total cholesterol was lower (5.2 vs 6.0 mmol/l, P= 0.003). Treatment for post-transplant diabetes mellitus was 18.5% versus 10.8% (P= 0.22). In both groups, antidiabetic medication could be withdrawn for most patients. This study indicates that tacrolimus is superior to cyclosporine-Neoral in preventing acute rejection with comparable patient and graft survival rates. Because of a lower need for treatment of hypertension and hypercholesterolemia, the cardiovascular risk profile is more favorable. A considerable proportion of patients can be successfully weaned off co-medication and treated with tacrolimus monotherapy.


Analysis of variance


Human leukocyte antigen


Hemolytic uremic syndrome


Mycophenolate mofetil


Panel-reactive antibodies


Rabbit anti-thy-mocyte globulin


  1. Top of page
  2. Abstract
  3. References
  • 1
    Basadonna GP, Matas AJ, Gillingham KJ, Payne WD, Dunn DL, Sutherland DER, Gores PF, Gruessner RWG, Najarian JS (1993) Early versus late acuterenal allograft rejection: impact on chronic rejection. Transplantation 55: 993995.
  • 2
    Basadonna GP, Matas AJ, Gillingham KJ, Payne WD, Dunn DL, Sutherland DER, Gores PF, Gruessner RWG, Arrazola L, Najarian JS (1993) Relationship between early vs late acute rejection and onset of chronic rejection in kidney transplantation. Transplant Proc 25: 910911.
  • 3
    Bertoni E, Zanazzi M, Rosati A, Maria L di, Moscarelli L, Piperno R, Conti P, Dedola G, Bandini S, Tosi P, Salvadori M (1998) Long-term steroid side effects, in renal transplantation need a safe steroid withdrawal: a single-center experience. Transplant Proc 30: 13031304.
  • 4
    Calne RY, Rolles K, White DJ, Thiru S, Evans DB, McMaster P, Dunn DC, Craddock GN, Henderson RG, Aziz S, Lewis P (1979) Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 2: 10331036.
  • 5
    Claesson K, Mayer AD, Squifflet J-P, Grabensee B, Eigler FW, Behrend M, Vanrenterghem Y, Hooff J van, Morales JM, Johnson RWG, Buchholz B, Land W, Forsythe JLR, Neumayer H-H, Ericzon B-G, Mühlbacher F (1998) Li-poprotein patterns in renal transplant patients: a comparison between FK506 and cyclosporin A patients. Transplant Proc 30: 12921294.
  • 6
    Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 3141.
  • 7
    Dimény E, Wahlberg J, Lithell H, Fellström B (1995) Hyperlipidaemia in renal transplantation - risk factor for long-term graft outcome. Eur J Clin Invest 25: 574583.
  • 8
    European Multicentre Trial Group (1983) Cyclosporine in cadaveric renal transplantation: one-year follow-up of a multicentre trial. Lancet 2: 986989.
  • 9
    Friman S, Bäckman L (1996) A new microemulsion formulation of cyclosporine: pharmacokinetic and clinical features. Clin Pharmacokinet 30: 181193.
  • 10
    Ghasemian SR, Light JA, Currier C, Sasaki TM, Aquino A (1999) Tacrolimus vs Neoral in renal and renal/pancreas transplantation. Clin Transplant 13: 123125.
  • 11
    Gjertson DW, Cecka JM, Terasaki PI (1995) The relative effects of FK506 and cyclosporine on short- and longterm kidney graft survival. Transplantation 60: 13841388.
  • 12
    Hall BM, Tiller DJ, Hardie I, Mahony J, Mathew T, Thatcher G, Miach P, Thomson N, Sheil AG (1988) Comparison of three immunosuppressive regimens in cadaver renal transplantation: long-term cyclosporine, short term cy-closporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine. N Engl J Med 318: 14991507.
  • 13
    Hohage H, Brückner D, Arlt M, Buchholz B, Zidek W, Spieker C (1996) Influence of cyclosporin A and FK506 on 24 h blood pressure monitoring in kidney transplant recipients. Clin Nephrol 45: 342344.
  • 14
    Hohage H, Arlt M, Brückner D, Dietl KH, Zidek W, Spieker S (1997) Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney transplant recipients. Clin Transplant 11: 225230.
  • 15
    Isaacs RB, Nock SL, Spencer CE, Connors AF, Wang X-Q, Sawyer R, Lobo PI (1999) Racial disparities in renal transplant outcomes. Am J Kidney Dis 34: 706712.
  • 16
    Ishikawa A, Flechner SM, Goldfarb DA, Myles JL, Modlin CS, Boparai N, Papajcik D, Mastroianni B, Novick AC (1999) Quantitative assessment of the first acute rejection as a predictor of renal transplant outcome. Transplantation 68: 13181324.
  • 17
    Jensik SC (1998) Tacrolimus (FK 506) in kidney transplantation: three-year survival results of the US multicenter, randomized, comparative trial. FK 506 Kidney Transplant Study Group. Transplant Proc 30: 12161218.
  • 18
    Jordan ML, Naraghi R, Shapiro R, Smith D, Vivas CA, Scantlebury VP, Gritsch HA, McCauley J, Randhawa P, Demetris AJ, McMichael J, Fung JJ, Starzl TE (1997) Tacrolimus rescue therapy for renal allograft rejection -five-year experience. Transplantation 63: 223228.
  • 19
    Jurewicz WA (1999) Immunological and nonimmunological risk factors with tacrolimus and Neoral in renal transplant recipients: an interim report. Transplant Proc 31 [Suppl 7A]: 64S66S.
  • 20
    Keown P, Niese D on behalf of the International Sandimmun Neoral Study Group (1998) Cyclosporine microemulsion increases drug exposure and reduces acute rejection without incremental toxicity in de novo renal transplantation. Kidney Int 54: 938944.
  • 21
    Knoll GA, Bell RC (1999) Tacrolimus versus cyclosporine for immunosup-pression in renal transplantation: metaanalysis of randomised trials. Br Med J 318: 11041107.
  • 22
    Land W, Schneeberger H, Schleibner S, Illner W-D, Abendroth D, Hillebrand G, Gokel JM, Albert E, Fornara P (1991) Long-term results in cadaveric renal transplantation under cyclosporine therapy. Transplant Proc 23: 12441246.
  • 23
    Lindholm A, Ohlman S, Albrechtsen D, Tufveson G, Persson H, Persson NH (1993) The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens. Transplantation 56: 307315.
  • 24
    Marcén R, Pascual J, Orofino L, Cal MA de la, Teruel JL, Villafruela JJ, Rivera ME, Burgos FJ, Mampaso F, Ortuno J (1998) The effect of delayed graft function and early graft rejection on renal transplant outcome. Transplant Proc 30: 17761777.
  • 25
    Matas A (1994) Chronic rejection in renal transplant recipients - risk factors and correlates. Clin Transplant 8: 332335.
  • 26
    Mayer AD, Dmitrewski J, Squifflet J-P, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, Hooff J van, Christiaans M, Morales JM, Andres A, Johnson RWG, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JLR, Talbot D, Neumayer H-H, Hauser I, Ericzon B-G, Brattström C, Claesson K, Mühlbacher F, Pohanka E (1997) Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection. A report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 64: 436443.
  • 27
    Mihatsch MJ, Kyo M, Morozumi K, Yamaguchi Y, Nickeleit V, Ryffel B (1998) The side-effects of cyclosporin A and tacrolimus. Clin Nephrol 49: 356363.
  • 28
    Morrissey PE, Gohh R, Shaffer D, Crosson A, Madras PN, Sahyoun AI, Monaco AP (1997) Correlation of clinical outcomes after tacrolimus conversion for resistant kidney rejection or cyclosporine toxicity with pathologic staging by the Banff criteria. Transplantation 63: 845848.
  • 29
    Morris-Stiff G, Ostrowski K, Balaji V, Moore R, Darby C, Lord R, Jurewicz WA (1998) Prospective randomised study comparing tacrolimus (Prograf) and cyclosporine (Neoral) as primary immunosuppression in cadaveric renal transplants at a single institution: interim report of the first 80 cases. Transpl Int 11[Suppl 1]: S334336.
  • 30
    Neylan JF for the US Renal Transplant Mycophenolate Mofetil Study Group (1997) Immunosuppressive therapy in high-risk transplant patients. Dose-dependent efficacy of mycophenolate mo-fetil in African-American renal allograft recipients. Transplantation 64: 12771282.
  • 31
    Niese D on behalf of the International Sandimmun Neoral Study Group (1995) A double-blind randomized study of Sandimmun Neoral versus Sandimmun in new renal transplant recipients: results after 12 months. Transplant Proc 27: 18491856.
  • 32
    Peschke B, Scheuermann EH, Geiger H, Bölscher S, Kachel H-G, Lenz T (1999) Hypertension is associated with hyperlipidemia, coronary heart disease and chronic graft failure in kidney transplant recipients. Clin Nephrol 51: 290295.
  • 33
    Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS for the FK 506 Kidney Transplant Study Group (1997) A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation 63: 977983.
  • 34
    Pollard SG, Lear PA, Ready AR, Moore RH, Johnson RWG on behalf of the UK Neoral Renal Study Group (1999) Comparison of microemulsion and conventional formulations of cyclosporin A in preventing acute rejection in de novo kidney transplant patients. Transplantation 68: 13251331.
  • 35
    Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Häyry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Marcussen N, Mihatsch MJ, Nadasdy T, Nickerson P, Olsen TS, Papadimitriou JC, Randhawa PS, Rayner DC, Roberts I, Rose S, Rush D, Salinas-Madrigal L, Salomon DR, Sund S, Taskinen E, Trpkov K, Yamaguchi Y (1999) The Banff 97 working classification of renal allograft pathology. Kidney Int 55: 713723.
  • 36
    Radermacher J, Meiners M, Bramlage C, Kliem V, Behrend M, Schlitt HJ, Pichlmayr R, Koch KM, Brunkhorst R (1998) Pronounced renal vasoconstriction and systemic hypertension in renal transplant patients treated with cyclosporin A versus FK 506. Transpl Int 11: 310.
  • 37
    Richards E, Schleibner S, Talbot D (1998) An exploratory analysis of prognostic factors for patient outcome during the first year following renal transplantation. European Tacrolimus Multicentre Renal Study Group. Transplant Proc 30: 13861388.
  • 38
    Roodnat JI, Zietse R, Mulder PGH, Rischen-Vos J, Gelder T van, IJzermans JNM, Weimar W (1999) The vanishing importance of age in renal transplantation. Transplantation 67: 576580.
  • 39
    Ruggenenti P, Gaspar F, Perna A, Remuzzi G (1998) Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes. Br Med J 316: 504509.
  • 40
    Schleibner S, Krauss M, Wagner K, Erhard J, Christiaans M, Hooff J van, Buist L, Mayer D (1995) FK506 versus cyclosporine in the prevention of renal allograft rejection: European pilot study - six-week results. Transpl Int 8: 8690.
  • 41
    Senel MF, Van Buren CT, Welsh M, Kahan BD (1998) Impact of early cyclosporine average blood concentration on early kidney transplant failure. Transpl Int 11: 4652.
  • 42
    Shapiro R, Jordan M, Scantlebury V, Fung J, Jensen C, Tzakis A, McCauley J, Carroll P, Ricordi C, Demetris AJ, Mitchell S, Jain A, Iwaki Y, Kobayashi M, Reyes J, Todo S, Hakala TR, Simmons RL, Starzl TE (1991) FK 506 in clinical kidney transplantation. Transplant Proc 23: 30653067.
  • 43
    Shapiro R, Jordan ML, Scantlebury VP, Vivas C, Fung JJ, McCauley J, Randhawa P, Demetris AJ, Irish W, Jain A, Mitchell S, Hakala TR, Simmons RL, Starzl TE (1995) A prospective, randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone in renal transplant patients. Transplant Proc 27: 814817.
  • 44
    Shapiro R, Jordan ML, Scantlebury VP, Vivas C, Marsh JW, McCauley J, Johnstone J, Randhawa P, Irish W, Gritsch HA, Naraghi R, Hakala TR, Fung JJ, Starzl TE (1999) A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/prednisone/mycophenolate mofetil in renal transplant recipients. Transplantation 67: 411415.
  • 45
    Solez K, Vincenti F, Filo RS (1998) Histopathologic findings from 2-year protocol biopsies from a US multicenter kidney transplant trial comparing tacrolimus versus cyclosporine. A report of the FK506 Kidney Transplant Study Group. Transplantation 66: 17361740.
  • 46
    Squifflet JP, Hooff JP van, Vanrenterghem Y (1999) The Benelux experience with the combination of tacrolimus and mycophenolate mofetil Transplant Proc 31 [Suppl 7A]: 72S4S.
  • 47
    Steroid Withdrawal Study Group (1999) Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil — a prospective randomized study. Transplantation 68: 18651874.
  • 48
    The Canadian Multicentre Transplant Study Group (1983) A randomized clinical trial of cyclosporine in cadaveric renal transplantation. N Engl J Med 309: 809815.
  • 49
    Undre NA, Hooff J van, Christiaans M, Vanrenterghem Y, Donck J, Heeman U, Kohnle M, Zanker B, Land W, Morales JM, Andrés A, Schäfer A, Stevenson P (1999) Low systemic exposure to tacrolimus correlates with acute rejection. Transplant Proc 31: 296298.
  • 50
    Vanrenterghem YFC (1995) Acute rejection and renal allograft outcome. Nephrol Dial Transplant 10[Suppl 1]: 2931.
  • 51
    Vanrenterghem Y, Squifflet JP, Forsy the J, Heeman U, Backman L, Taube D, Morales JM, Ekberg H, Hooff J van, Zanker B, Dietl KH, Talbot D, Hauser I, Tyden G, Claesson K, Mühlbacher F (1998) Co-administration of tacrolimus and mycophenolate mofetil in cadaveric renal transplant recipients. Transplant Proc 30: 12901291.
  • 52
    Vincenti F, Laskow DA, Neylan JF, Mendez R, Matas AJ (1996) One-year follow up of an open-label trial of FK506 for primary kidney transplantation. Transplantation 61: 15761581.
  • 53
    Woodle ES, Cronin D, Newell KA, Millis JM, Bruce DS, Piper JB, Haas M, Josephson MA, Thistlethwaite JR (1996) Tacrolimus therapy for refractory acute renal allograft rejection. Definition of the histologic response by protocol biopsies. Transplantation 62: 906910.
  • 54
    Woodle ES, Thistlethwaite JR, Gordon JH, Laskow D, Deierhoi MH, Burdick J, Pirsch JD, Sollinger H, Vincenti F, Burrows L, Schwartz B, Danovitch GM, Wilkinson AH, Shaffer D, Simpson MA, Freeman RB, Rohrer RJ, Mendez R, Aswad S, Munn SR, Wiesner RH, Delmonico FL, Neylan J, Whelchel J (1996) A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group. Transplantation 62: 59499.
  • 55
    Yokoyama I, Uchida K, Fukao K, Ochiai T, Takahashi K, Endo T, Oshima S, Ishibashi M, Takahara S, Iwasaki Y, Ota K, Takagi H, Sonoda T for the Japanese FK 506 Study Group (1995) FK 506: long-term study in kidney transplantation. Transplant Proc 27: 818821.