A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation

Claudio Ponticelli, Antonio Tarantino, Giuseppe P. Segoloni, Vincenzo Cambi, Gaetano Rizzo, Paolo Altieri, Francesco Mastrangelo, Marco Castagneto, Maurizio Salvadori, Umberto Valente, Maria Cossu, Stefano Federico, Francesco Pisani, Giuseppe Montagnino, Maria Messina, Luca Arisi, Mario Carmellini, Gianbenedetto Piredda, Giuseppe Corbetta

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43 Citations (Scopus)

Abstract

Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P <0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, whereas those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomisation had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P <0.0001), osteomuscular (P <0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P <0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early posttransplant period.

Original languageEnglish
Pages (from-to)638-646
Number of pages9
JournalJournal of the American Society of Nephrology
Volume8
Issue number4
Publication statusPublished - Apr 1997

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Kidney Transplantation
Cyclosporine
Graft Survival
Steroids
Therapeutics
Transplants
Kidney
Creatinine
Intention to Treat Analysis
Azathioprine
Random Allocation
Polycystic Kidney Diseases
Complementary Therapies
Glomerulonephritis
Hypercholesterolemia
Cadaver
Systemic Lupus Erythematosus
Renal Insufficiency

ASJC Scopus subject areas

  • Nephrology

Cite this

Ponticelli, C., Tarantino, A., Segoloni, G. P., Cambi, V., Rizzo, G., Altieri, P., ... Corbetta, G. (1997). A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. Journal of the American Society of Nephrology, 8(4), 638-646.

A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. / Ponticelli, Claudio; Tarantino, Antonio; Segoloni, Giuseppe P.; Cambi, Vincenzo; Rizzo, Gaetano; Altieri, Paolo; Mastrangelo, Francesco; Castagneto, Marco; Salvadori, Maurizio; Valente, Umberto; Cossu, Maria; Federico, Stefano; Pisani, Francesco; Montagnino, Giuseppe; Messina, Maria; Arisi, Luca; Carmellini, Mario; Piredda, Gianbenedetto; Corbetta, Giuseppe.

In: Journal of the American Society of Nephrology, Vol. 8, No. 4, 04.1997, p. 638-646.

Research output: Contribution to journalArticle

Ponticelli, C, Tarantino, A, Segoloni, GP, Cambi, V, Rizzo, G, Altieri, P, Mastrangelo, F, Castagneto, M, Salvadori, M, Valente, U, Cossu, M, Federico, S, Pisani, F, Montagnino, G, Messina, M, Arisi, L, Carmellini, M, Piredda, G & Corbetta, G 1997, 'A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation', Journal of the American Society of Nephrology, vol. 8, no. 4, pp. 638-646.
Ponticelli C, Tarantino A, Segoloni GP, Cambi V, Rizzo G, Altieri P et al. A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. Journal of the American Society of Nephrology. 1997 Apr;8(4):638-646.
Ponticelli, Claudio ; Tarantino, Antonio ; Segoloni, Giuseppe P. ; Cambi, Vincenzo ; Rizzo, Gaetano ; Altieri, Paolo ; Mastrangelo, Francesco ; Castagneto, Marco ; Salvadori, Maurizio ; Valente, Umberto ; Cossu, Maria ; Federico, Stefano ; Pisani, Francesco ; Montagnino, Giuseppe ; Messina, Maria ; Arisi, Luca ; Carmellini, Mario ; Piredda, Gianbenedetto ; Corbetta, Giuseppe. / A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. In: Journal of the American Society of Nephrology. 1997 ; Vol. 8, No. 4. pp. 638-646.
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abstract = "Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97{\%} in monotherapy, 91{\%} in double therapy, and 96{\%} in triple therapy; the graft survival including death was 84{\%}, 77{\%}, and 88{\%}, respectively; and the pure graft survival was 87{\%}, 85{\%} and 91{\%}, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P <0.01). Of the patients on monotherapy, 52{\%} were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68{\%}, and the pure graft survival was 72{\%}, in comparison with 93{\%} and 94{\%}, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, whereas those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomisation had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P <0.0001), osteomuscular (P <0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P <0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early posttransplant period.",
author = "Claudio Ponticelli and Antonio Tarantino and Segoloni, {Giuseppe P.} and Vincenzo Cambi and Gaetano Rizzo and Paolo Altieri and Francesco Mastrangelo and Marco Castagneto and Maurizio Salvadori and Umberto Valente and Maria Cossu and Stefano Federico and Francesco Pisani and Giuseppe Montagnino and Maria Messina and Luca Arisi and Mario Carmellini and Gianbenedetto Piredda and Giuseppe Corbetta",
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T1 - A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation

AU - Ponticelli, Claudio

AU - Tarantino, Antonio

AU - Segoloni, Giuseppe P.

AU - Cambi, Vincenzo

AU - Rizzo, Gaetano

AU - Altieri, Paolo

AU - Mastrangelo, Francesco

AU - Castagneto, Marco

AU - Salvadori, Maurizio

AU - Valente, Umberto

AU - Cossu, Maria

AU - Federico, Stefano

AU - Pisani, Francesco

AU - Montagnino, Giuseppe

AU - Messina, Maria

AU - Arisi, Luca

AU - Carmellini, Mario

AU - Piredda, Gianbenedetto

AU - Corbetta, Giuseppe

PY - 1997/4

Y1 - 1997/4

N2 - Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P <0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, whereas those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomisation had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P <0.0001), osteomuscular (P <0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P <0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early posttransplant period.

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