J.L Teruel

Influence of immunosuppression on the prevalence of cancer after kidney transplantation.

The prevalence of cancer in renal transplant patients is greater than in the general population. It is influenced by demographic and ethnic characteristics. We performed a retrospective study of 793 patients who received 872 kidney transplants at our center during 23 years. The age at transplantation was 41.4+/-14.0 years, the follow up 75.4+/-69.4 months. The cohorts include 203 patients treated with azathioprine-prednisone; 510, cyclosporine-based therapy; and 159, tacrolimus-based therapy. There were 95 patients (10.9%) who developed at least one neoplasm with 9 having more than one type of tumor. The incidence was of 17.3 cases per 1000 patients-years. Forty-four (46.3%) had skin cancer, 8 (8.4%) Kaposi sarcoma and 43 (45.3%) a non-skin cancer. Seven of eight patients with Kaposi sarcoma were on CsA therapy. The risk of developing a neoplasm at 5, 10, and 15 years was 8%, 17%, and 30% respectively. In a multivariate analysis, the risk factors associated with neoplastic diseases were older age (OR=1.061; 95% CI 1.039-1.084; P=.000), male sex (OR=2.658; 95% CI 1.536-4.599; P=.000), length of follow-up (OR=1.121; 95% CI 1.073-1.172; P =.000), and immunosuppression with CsA (OR=4.448; 95% CI 1.334-14.764; P=.015). Cancer was the cause of death in 26 patients, the fourth most common cause after cardiovascular disease, infection, and liver failure. We conclude that malignancies are an important cause of morbidity and mortality among transplant patients. Special attention must be devoted to older male patients with a long-term follow up to develop preventive and surveillance strategies.

Effects of the new immunosuppressive agents on the occurrence of malignancies after renal transplantation.

INTRODUCTION The risk of malignancies in renal transplant recipients is considerably greater than in the general population. The purpose of the present study was to investigate the effects on the appearance of malignancies of 3 immunosuppressive periods: azathioprine (AZA), cyclosporine (CsA), and tacrolimus (TAC). PATIENTS AND METHODS This study included 1029 first renal transplant recipients of mean age at transplantation of 44.6±14.9 years with a mean follow-up of 95.6±84.2 months. Initial immunosuppression was AZA-based (n=198), CsA-based (n=524), and TAC (n=307). A total of 280 recipients were also treated with mycophenolate mofetil or mycophenolic acid. RESULTS There were 157 patients (15.3%) who displayed≥1 malignancy; there were 95 skin (9.2%) and 74 (7.8%) non-skin malignancies with presentations at 74±62 and 107±77 months, respectively (P=.003). The skin malignancies included squamous cell carcinomas (n=41), basal cell carcinomas (n=41), Kaposi sarcomas (n=7), and melanomas (n=4). Among the solid tumors, lymphoproliferative disorders (n=15), digestive tract (n=14), kidney and urinary tract (n=11), lung (n=10), and breast (n=3) carcinomas. The cumulative incidences at 5, 10, and 15 years were 6%, 10%, and 18% for skin and 3%, 7%, and 14% for non-skin malignancies, respectively. Multivariate analysis showed that age at transplant in years (P=.000) and male gender (P=.000) were the only variables associated with skin malignancies; age at transplant in years (P=.004) and treatment with OKT3 (P=.000) were associated with non-skin malignancies. Malignancies were the cause of death in 18% of recipients who died with functioning grafts. CONCLUSION Malignancies are an important cause of morbidity and mortality among renal transplant recipients. The new immunosuppressive agents do not increase the risk of malignancies. Special surveillance is needed for older, male recipients.

Renal transplant recipient outcome after losing the first graft

Renal transplantation is the optimal therapy for end-stage renal failure and considerable attention has been given to graft and patient survival and the effectiveness of immunosuppressive regimens. However, little attention has been given to outcome for patients who lose their grafts. We retrospectively reviewed the outcomes of the 793 first renal transplants performed at our institution between November 1979 and December 2001. A total of 348 patients lost their grafts, 116 by death with a functioning graft (33.3%) and 232 patients for other causes (66.7%). Eighty-six patients (37.1%) received a second transplant 3.5+/-2.4 years after returning to dialysis and the remainder continued on dialysis. Retransplanted patients were younger at the time of the first transplant (P=.000), and both time on dialysis (P=.012) and duration of graft function (P=.057) were shorter than for those remaining on dialysis. Therefore, retransplant patient survival at 1, 5, and 10 years was better than among those patients on dialysis not included on the waiting list (P<.001), but when compared with the relisted patients the survival rate was almost identical (96%, 85%, and 67% vs 97%, 82%, and 67%; P=NS). Almost 40% of patients who lost their first grafts were retransplanted. We did not observe differences in patient survival between retransplant and relisted patients. Because the number of cases is limited, our results need to be confirmed by larger series.

Comparison of C0 and C2 cyclosporine monitoring in long-term renal transplant recipients

Recent data show that monitoring cyclosporine A (CsA) concentrations with 2-hour postdose levels (C2) correlates with the incidence of rejection and graft outcome in de novo renal transplant patients. The purpose of the present work was to evaluate the advantage of C2 monitoring after the first year of kidney transplantation. We studied 161 patients, 96 on CsA-prednisone and 65 on triple therapy (Aza or MMF) who had been transplanted for a mean of 103+/-44 months. Mean serum creatinine (SCr) was 1.65+/-0.69 mg/dL, mean C0 was 174+/-44, and C2 was 667+/-194 ng/mL. Patients were classified according to C2 values: >850 (n=29), between 850 and 450 (n=109), and <450 (n=23) ng/mL. Patients with C2 <450 ng/mL displayed higher SCr values (1.97+/-0.99; 1.59+/-0.51; 1.52+/-0.4 mg/dL; P<.001), received lower CsA doses (172+/-54; 207+/-54; 227+/-56 mg/d, P<.01), showed lower C0 levels (155+/-48; 172+/-41; 199+/-45 ng/mL; P< .001), and included more patients on triple therapy (54.5%; 44%; 17.2%; P<.05). We found weak correlations between C0 and C2 (r=0.37), between C2 and CsA dose (r=0.36), and between C0 and SCr (r=-0.37). Among 117 patients followed up for 1 year with several C0 and C2 measurements, the coefficient of variation of C0 was 17% and of C2 was 21%. Graft functional deterioration occurred in 16 patients independent of the differences among the C2 groups, but 7 recipients (43.7%) had C0 <150 ng/mL and C2/C0 >5. We conclude that C2 in monitoring stable patients needs further evaluation.