Three-year outcomes in kidney transplant patients randomized to steroid-free immunosuppression or steroid withdrawal, with enteric-coated mycophenolate sodium and cyclosporine: the infinity study.

In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA) induction, enteric-coated mycophenolate sodium (EC-MPS: 2160 mg/day to week 6, 1440 mg/day thereafter), and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal). The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR) graft loss, death, or loss to follow-up) occurred in 21.4% (95% CI 11.8-31.0%) of steroid avoidance patients and 16.4% (95% CI 7.1-25.7%) of steroid withdrawal patients by month 36 (P = 0.46). BPAR had occurred in 20.0% and 11.5%, respectively (P = 0.19). The incidence of adverse events with a suspected relation to steroids during months 6-36 was 22.9% versus 37.1% (P = 0.062). By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months.

Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

Acute disseminated encephalomyelitis in two renal transplant patients: is there a role for Epstein-Barr virus reactivation?

Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system, usually occurring after a vaccination or infectious disease. It has been exceptionally described in transplanted patients. The pathophysiology remains incompletely understood. We report the clinical, biological and magnetic resonance imaging (MRI) presentation and evolution of two kidney-transplanted patients with ADEM associated with local Epstein-Barr virus (EBV) reactivation. ADEM may occur in transplanted patients with favorable evolution. Its pathophysiology is uncertain, and the implication of EBV is discussed.

Five-year results of a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation: the SPIESSER study.

Calcineurin inhibitors improve acute rejection rates and short-term graft survival in renal transplantation, but their continuous use may be deleterious. We evaluated the 5-year outcomes of sirolimus (SRL) versus cyclosporine (CsA) immunosuppressive treatment. This observational study was an extension of the SPIESSER study where deceased donor kidney transplant recipients were randomized before transplantation to a SRL- or CsA-based regimen and followed up 1 year. Data from 131 (63 SRL, 68 CsA) out of 133 patients living with a functional graft at 1 year were collected retrospectively at 5 years posttransplant. Seventy percent of CsA patients versus 54% of SRL patients were still on the allocated treatment at 5 years (p = 0.091), most discontinuations in each group being due to safety issues. In intent-to-treat, mean MDRD eGFR was higher with SRL: 54.2 versus 45.3 mL/min with CsA (p = 0.019); SRL advantage was greater in on-treatment analyses. There were no differences for patient survival (p = 0.873), graft survival (p = 0.121) and acute rejection (p = 0.284). Adverse events were more frequent with SRL (80% vs. 60%, p = 0.015). Results confirmed the high SRL discontinuation rate due to adverse events. Nevertheless, a benefit was evidenced on renal function in patients (more than 50%) still on treatment at 5 years.

Comparison of C4d detection on erythrocytes and PTC-C4d to histological signs of antibody-mediated rejection in kidney transplantation.

C4d on erythrocytes (EC4d), C4d peritubular capillary deposition (PTC-C4d) staining and histology were compared in a cross-sectional cohort of 146 renal allograft biopsies (132 patients). EC4d levels paralleled PTC-C4d staining, but were more predictive of peritubular capillaritis (PTC). Donor-specific antibodies (DSA), PTC-C4d, EC4d and PTC were analyzed in an independent longitudinal follow-up cohort (96 biopsies, 76 patients). Seventy-six samples were PTC and EC4d concordant, 11 positive and 65 negative, 7 PTC-EC4d+ and 13 PTC+EC4d-. EC4d levels were related to DSA occurrence. With ABMR defined by PTC and DSA, all apparently discordant patients, EC4d negative, were correctly reassigned comparing EC4d level curves with rejection kinetics, with positive EC4d samples predating biopsy or late biopsies compared with ABMR flare-ups. All EC4d-positive patients without PTC or DSA had permanent high EC4d levels unrelated to rejection. EC4d was more abundant in PTC-positive (mean = 108.5%± 3.4; n = 50) than PTC-negative samples (mean = 88.1%± 1.3; n= 96; p < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value of PTC-C4d and EC4d for PTC were, respectively, 75%, 79%; 64%, 76% (p < 0.05); 28%, 46% (p < 0.05) and 93%, 94%. Values were similar for DSA. A noninvasive blood test, EC4d, and particularly longitudinally monitoring EC4d levels, may increase surrogate ABMR testing options.

The influence of cytomegalovirus infections on patient and renal graft outcome: a 3-year, multicenter, observational study (Post-ECTAZ Study).

Cytomegalovirus (CMV) infections posttransplant may increase the risk of acute rejection, graft failure, patient death, opportunistic infections, malignancy, diabetes, and cardiovascular complications. ECTAZ, a multicenter, randomized trial compared safety and efficacy at 12 months (M12) of two doses daclizumab (54 patients, group D) with thymoglobulin (55 patients, group T), plus cyclosporine (CsA), mycophenolate mofetil and steroids in first cadaveric kidney transplant patients. D+/R- patients received oral ganciclovir prophylaxis for 90 days. Post-ECTAZ is a 36-month, multicenter, observational study including recipients who participated in ECTAZ trial. We studied the indirect effects of CMV infections, whether recipients experienced (CMVi+) or not (CMVi-) a CMV infection/syndrome/disease. We compared 49 patients in the group CMVi+ with 54 patients in the group CMVi-. At month 36 (M36), patient survival, graft survival and renal function were comparable. The incidence of biopsy-proven acute rejection was 16.3% in the CMVi+ group versus 24.1% in the CMVi- group (not significant). The incidence of infections was increased in the CMVi+ group (P = .004), but not diabetes, malignancies, and cardiovascular complications. Our study shows at M36 that CMV infection/syndrome/disease episodes were associated with a higher incidence of infections but no difference for other long-term complications. Our data suggest that anti-CMV prophylaxis could decrease the risk for long-term related CMV complications.

Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF-four-year results of the Postconcept study.

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function. We previously reported that conversion from cyclosporine A (CsA) to sirolimus (SRL) 3 months after transplantation significantly improved renal function at 1 year. In the Postconcept trial, 77 patients in the SRL group and 85 in the CsA group were followed for 48 months. Renal function (Cockcroft and Gault) was significantly better at month 48 (M48) in the SRL group both in the intent-to-treat population (ITT): 62.6 mL/min/1.73 m(2) versus 57.1 mL/min/1.73 m(2) (p = 0.013) and in the on-treatment population (OT): 67.5 mL/min/1.73 m(2) versus 57.4 mL/min/1.73 m(2) (p = 0.002). Two biopsy proven acute rejection episodes occurred after M12 in each group. Graft and patient survival were comparable (graft survival: 97.4 vs. 100%; patient survival: 97.4 vs. 97.6%, respectively). The incidence of new-onset diabetes was numerically increased in the SRL group (7 vs. 2). In OT, three cancers occurred in the SRL group versus nine in the CsA group and mean proteinuria was increased in the SRL group (0.42 ± 0.44 vs. 0.26 ± 0.37; p = 0.018). In summary, the renal benefits associated with conversion of CsA to SRL, at 3 months posttransplantation, in combination with MMF were maintained for 4 years posttransplantation.

Optimization of initial tacrolimus dose using pharmacogenetic testing.

Retrospective studies have demonstrated that patients who are expressors of cytochrome P4503A5 (CYP3A5) require a higher tacrolimus dose to achieve a therapeutic trough concentration (C(0)). The aim of this study was to evaluate this effect prospectively by pretransplantation adaptation. We randomly assigned 280 renal transplant recipients to receive tacrolimus either according to CYP3A5 genotype or according to the standard daily regimen. The primary end point was the proportion of patients within the targeted C(0). Secondary end points included the number of dose modifications and the delay in achieving the targeted C(0). In the group receiving the adapted dose, a higher proportion of patients had values within the targeted C(0) at day 3 after initiation of tacrolimus (43.2% vs. 29.1%; P = 0.03); they required fewer dose modifications, and the targeted C(0) was achieved by 75% of these patients more rapidly. The clinical end points were similar in the two groups. Pharmacogenetic adaptation of the daily dose of tacrolimus is associated with improved achievement of the target C(0). Whether this improvement will affect clinical outcomes requires further evaluation.

Interstitial fibrosis quantification in renal transplant recipients randomized to continue cyclosporine or convert to sirolimus.

Conversion from cyclosporine (CsA) to sirolimus at week 12 after kidney transplantation is associated with a significant improvement in renal function. The aim of this analysis was to investigate the effect of this conversion on interstitial fibrosis (IF), a hallmark of chronic allograft injury, in patients taking part in the CONCEPT trial. This multicenter, prospective, trial included 193 renal recipients randomized at week 12 to switch from CsA to sirolimus or to continue CsA, with mycophenolate mofetil. Routine biopsy with automated, quantified assessment of IF by a program of color segmentation was performed at 1 year in 121 patients. At 1 year, renal function was significantly improved in the conversion group as assessed by estimated GFR (MDRD) and measured GFR. Biopsy results, however, showed no between-group difference in percentage of IF. Calculated GFR at 1 year was significantly associated with the percentage of IF (p = 0.004, R(2)= 0.07). By multivariate analysis diabetic patients had more fibrosis than non-diabetic patients. In conclusion, although kidney transplant patients converted from CsA to sirolimus showed significant improvement in renal function, we found no difference of IF on 1-year biopsies.

Efficacy on renal function of early conversion from cyclosporine to sirolimus 3 months after renal transplantation: concept study.

Sirolimus (SRL) allows to minimize the use of cyclosporine (CsA), but de novo administration after transplantation is associated with various complications. We report a prospective, open-label, multicenter randomized study to evaluate conversion from a CsA-based regimen to a SRL-based regimen 3 months after transplantation. One hundred ninety-two of a total of 237 patients were eligible at 3 months to be converted to SRL (n = 95) or to continue CsA (n = 97). All patients were also given mycophenolate mofetil (MMF) and oral steroids, planned to be discontinued at month 8. The primary endpoint, the clearance estimated according to Cockcroft and Gault at week 52, was significantly better in the SRL group (68.9 vs. 64.4 mL/min, p = 0.017). Patient and graft survival were not statistically different. The incidence of acute rejection episodes, mainly occurring after withdrawal of steroids, was numerically but not statistically higher in the SRL group (17% vs. 8%, p = 0.071). Sixteen patients discontinued SRL, mainly for adverse events (n = 11), and seven patients discontinued CsA for renal failure or acute rejection. Significantly, more patients in the SRL group reported aphthous, diarrhea, acne and high triglyceride levels. Conversion CsA to SRL 3 months after transplantation combined with MMF is associated with improvement in renal function.

Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids.

To evaluate the efficacy and tolerance of a calcineurin inhibitor (CNI)-free regimen, 145 renal recipients were prospectively randomized to receive either sirolimus (n = 71) or cyclosporine (CsA; n = 74). All patients received polyclonal antilymphocyte antibodies, mycophenolate mofetil (MMF) and steroids (6 months). The primary endpoint, estimated glomerular filtration rate (eGFR) was not significantly different at 12 months comparing sirolimus- and CsA-treated patients (60 +/- 27 vs. 57 +/- 21 mL/min). At 12 months, patient and graft survival, incidence of biopsy-proven rejection and rates of steroid withdrawal were not statistically different (97% vs. 97%; 90% vs. 93%; 14.3% vs. 8.6% and 82.8% vs. 84.1%, respectively). Delayed and slow graft function (SGF) was not significantly different (18.6% vs. 12.3% and 11.4% vs. 13.7%, respectively). In patients who remained on treatment according to protocol at 12 months, eGFR was significantly higher with sirolimus (69 +/- 19 vs. 60 +/- 14 mL/min, p = 0.01). Overall study drug discontinuation rates were 28.2% with sirolimus and 14.9% with CsA. Adverse events (wound complications, mouth ulcers, diarrhea, hypokalemia, bronchopneumonia) and proteinuria >0.5 g/24h (38.8% vs. 5.6%, p < 0.001) were significantly more frequent in sirolimus-treated patients. Cytomegalovirus (CMV) infections were significantly less frequent with sirolimus (6% vs. 23%, p < 0.01). A CNI-free regimen using sirolimus-MMF can achieve excellent renal function, but patients on sirolimus experienced a high rate of adverse events and study drug discontinuation.

Long-term results of monoclonal anti-Il2-receptor antibody versus polyclonal antilymphocyte antibodies as induction therapy in renal transplantation.

We compared the influence of induction therapy on 5-year patient and graft survival as well as on renal function in 100 kidney graft recipients at low immunological risk treated with antilymphocyte globulin (n = 50) versus anti-IL-2R monoclonal antibody (n = 50) in a prospective multicenter study. Long-term immunosuppressive treatment included cyclosporine, mycophenolate mofetil, and a short course of steroids in all patients. Five year graft (86% vs 86%) and patient (94% vs 94%) survivals were identical in both study arms. Moreover, neither serum creatinine or proteinuria were significantly different between the two groups. Our results showed that the choice of the induction therapy seemed to not have a major impact on long-term outcomes among renal recipients at low immunological risk.

[Pregnancy after renal transplantation. Obstetrical follow-up and impact on renal graft function]. / Grossesse après transplantation rénale. Suivi obstétrical et retentissement sur le greffon rénal.

OBJECTIVE: The aim of this study is to give the results of our experience about pregnancies among the renal transplantation patients and to assess the impact of the pregnancy on renal graft function. PATIENTS AND METHODS: Twenty pregnancies from 17 renal transplant recipients were analysed and long-term outcome of the renal graft was studied. We analysed the outcomes from clinical and biological data before, during and after pregnancy. RESULTS: Mean patient age was 30.3+/-3.5 years and meantime between transplantation and the onset of pregnancy was 62.4+/-34.5 months. There was no significant difference between the biological data before and after pregnancy. We did not observe any acute rejection. The mean maternal complications were preeclampsia in 35%, low birth weight in 39%, prematurity in 45% and cesarean sections in 55%. There is no impact of the pregnancy on the renal graft during the follow-up (3 years). The follow-up revealed 2 cases of chronic rejection. DISCUSSION AND CONCLUSION: A multi-disciplinary approach of pregnancy in renal recipients and an interval of 2 years after kidney transplantation are necessary. There are more complications during pregnancy without increased risks of graft lose.

Virological and histological responses to one year alpha-interferon-2a in hemodialyzed patients with chronic hepatitis C.

BACKGROUND: alpha-Interferon-2a (IFNalpha) alone is a therapy of limited proven benefit for non-uremic patients with chronic hepatitis C virus (HCV) infection. In dialyzed patients, such an effect is suggested on small short-term studies without sufficient clinical and virologic follow-up to document any sustained effect. PROTOCOL: Twelve chronically hemodialyzed patients with chronic hepatitis C and waiting for renal transplantation were included in a prospective open study of treatment with IFNalpha. We used, as did others, doses of 3 million units (MU), three times a week, but for a longer period of treatment of 12 months. Follow-up was continued for 6 months after the end of IFNalpha in order to document any sustained biochemical, virological and histological responses. RESULTS: Aminotransferase levels returned to the normal range within 1-2 months of treatment in all patients in whom they had been elevated at baseline. At 1 month of treatment, serum HCV-RNA was not detected in 5 (41%) patients and in 9 (75%) at 12 months. A sustained virological response was documented in 4 (33%) patients 6 months after the end of treatment. Relapse occurred in 5 patients within 2 months after IFNalpha withdrawal. HCV genotype was not predictive of any sustained response. At inclusion, using the histologic Metavir scoring system, half of the patients had low-grade cytolytic activity and none had cirrhosis. After IFNalpha, liver biopsy specimens were available from 9 patients and showed histologic improvement in 3. IFNalpha tolerance was poor, inducing a 5% mean weight loss and the acute rejection of two nonfunctioning kidney grafts. CONCLUSION: This study documents that administration of IFNalpha at 3 MU three times a week, for 12 months, in hemodialysis patients with chronic hepatitis C was efficient for clearing the serum of HCV-RNA in 75% of the patients. A sustained response was maintained in one third of these patients after cessation of IFNalpha, and was predicted by the early serum clearance of the virus within the first 2 months of treatment. We confirm that a 12-month treatment period carries a higher sustained response rate than shorter treatment periods. These encouraging results call for larger studies in uremic patients, using IFNalpha alone or in association with new antiviral drugs.

Factors predicting the long-term success of maintenance cyclosporine monotherapy after kidney transplantation.

BACKGROUND: The theoretical aim of maintenance cyclosporine monotherapy (mCsA) after kidney transplantation is to reduce the incidence of the metabolic complications of corticosteroids and to minimize the adverse effects of excessive long-term immunosuppression. This study was performed in low-immunological-risk cadaveric kidney transplant recipients to evaluate the risks and benefits of mCsA and the long-term graft survival, and to determine the factors predicting success of this policy. METHODS: The multicenter retrospective study was conducted in 329 Caucasian patients receiving mCsA out of 728 first cadaveric kidney transplant recipients. The inclusion criteria were: HLA antibodies < or =25%, serum creatinine <200 micromol/L, and no rejection or only one rejection episode. At the end of the study, we compared the group of patients successfully treated with mCsA (successful group) with those requiring additional immunosuppressive agents (unsuccessful mCsA group). RESULTS: Overall patient and graft survival rates for the 728 first cadaveric graft were 92% and 64%, respectively, at 8 years. Out of 329 patients enrolled in mCsA, 240 were maintained on this treatment and 89 were withdrawn (3 deaths, 18 graft losses, 68 functional grafts). The 8-year graft survival in the 329 enrolled mCsA patients was 84%, 95% in the successful mCsA group, and 70% in the unsuccessful mCsA group. Multivariate analysis showed that the factors predicting success of mCsA were: donor age <40 years (P = 0.001), serum creatinine at mCsA initiation <125 micromol/L (P = 0.02), no rejection episode before mCsA initiation (P = 0.005), and glomerulopathy as the primary renal disease (P = 0.001). CONCLUSION: Numerous kidney transplant recipients with a low immunological risk and good and stable renal function may benefit from discontinuation of prednisone and azathioprine in order to reduce the complications related to these drugs. This therapeutic approach had no adverse impact on the overall long-term graft survival for "low risk" and successful patients.

Cytomegalovirus-related disease and risk of acute rejection in renal transplant recipients: a cohort study with case-control analyses.

The relationship between a cytomegalovirus (CMV) infection and the acute rejection of a renal transplant is not well established. The aim of the study was to document whether the clinical presentation of a CMV infection as a diffuse inflammatory disease or as a clinically asymptomatic illness is a risk factor of acute renal transplant rejection. One hundred and ninety-two consecutive renal transplant recipients were included in a historical cohort study for exposed-non exposed analyses. CMV infection after transplantation was the exposure factor. Before transplantation, 113 patients had antibodies against CMV and 79 were seronegative. The patients were divided into three groups: Group 1 consisted of 64 patients who had neither clinical signs of CMV disease nor CMV serological changes after transplantation, Group 2 consisted of 77 seropositive patients with asymptomatic viremia, and Group 3 consisted of 51 seropositive patients with clinical signs of diffuse inflammation that included fever, neutropenia, and various visceral involvements (CMV disease). Groups 2 and 3, the seropositive patients, were paired with Group 1 patients. Acute rejection was considered as CMV-induced when it occurred within one month following viremia, during the first year after transplantation. Transplant patients with CMV disease, had a significant likelihood of developing acute rejection after CMV infection or reactivation (P < 0.01). The odds ratio for developing rejection was 5.98, 95% confidence interval: 1.21-29.40. Such a link was not documented for recipients with asymptomatic CMV infection. In conclusion, CMV disease, but not asymptomatic viremia, is a risk factor of acute renal transplant rejection. On epidemiological grounds, these results support the hypothesis that factors controlling both the viral replication and the diffuse inflammatory process are implicated in acute graft rejection.

[Cytomegalovirus infection, a risk factor for acute graft rejection in renal transplant recipients. A case-controlled study]. / La maladie à cytomégalovirus, facteur de risque de rejet aigu d'allogreffe rénale. Etude exposés/non exposés.

OBJECTIVES: We studied the relationship between cytomegalovirus infection and episodes of acute rejection after infection in renal graft recipients at the Reims University Hospital from 1989 to 1995. PATIENTS AND METHODS: Two exposed versus nonexposed analyses were conducted, one (series 1) for CMV infection and the other (series 2) for CMV disease. For each analysis, exposed recipients were matched with nonexposed recipients for date of graft (+/- 6 months). Risk of acute rejection was assessed with univariate analysis then with multivariate analysis using logistic regression. RESULTS: Among the 192 graft recipients included, 64 developed CMV infection, 77 had an infection (series 1) and 51 had CMV disease (series 2). In series 1, only failure of renal graft was a significant risk factor of acute rejection (OR = 10.4; 95% Cl 1.9-56.3). CMV infection was not a significant risk factor (OR = 1.06; 95% Cl 0.2-5.6). Conversely, in series 2, there was a 6-fold increase in the risk of acute rejection in recipients who developed CMV disease (OR = 5.98; 95% Cl 1.21-29.4). CONCLUSION: The fact that CMV disease and not CMV infection is a risk factor of acute rejection in renal transplant recipients is an argument for implicating a general inflammatory reaction characteristic of CMV disease in the pathogenesis of acute rejection. This finding favors preventive treatment of CMV infection.

Maintenance cyclosporin monotherapy after renal transplantation--clinical predictors of long-term outcome.

BACKGROUND: There is considerable debate about whether maintenance cyclosporin (CsA) monotherapy is advisable or not in renal transplantation. METHODS: Between August 1984 and December 1989, 463 adult patients received a first cadaver graft. Initial immunosuppression was sequential: antilymphocyte or antithymocyte globulins (10-14 days), prednisone and azathioprine were combined and CsA was introduced (6-8 mg/kg/day) when the antilymphocyte or antithymocyte globulins were discontinued. When the graft function was stable and the peak of preformed lymphocytotoxic antibodies was < or = 25% and/or the number of rejection episodes was < or = 1, the steroid therapy was stopped within 1.5-3 months after transplantation, and azathioprine within 3-12 months. Patients with both anti HLA antibodies > 25% and more than one rejection episode were excluded. Cyclosporin doses were adapted for whole-blood trough levels between 100 and 200 ng/ml (monoclonal antibody radioimmunoassay or high-performance liquid chromatography). Cyclosporin monotherapy was attempted in 234 of the 463 patients. RESULTS: At the end of the investigation in January 1993 (follow-up time > 36 months, mean 60.5 +/- 4.5 months), 135 patients were receiving CsA without steroids or azathioprine. The 99 CsA monotherapy failures were due to rejection episodes in 48 cases, CsA A nephrotoxicity in 26 cases, and other causes in 25 cases, including five deaths and four with poor compliance. Renal function was stable in patients with successful CsA monotherapy: mean creatininaemia was 124 +/- 10 mumol/l at the time of CsA monotherapy inclusion and 129 +/- 10 mumol/l at the end of follow-up (mean time of CsA monotherapy 52 +/- 6 months). The parameters for predicting monotherapy success were age (43.2 versus 37.8. P = 0.0014), timing of trial inclusion > or = 6 months post-transplant (7.9 +/- 3 versus 5.3 +/- 3.1 months, P = 0.04), and excellent and stable renal function at the time of inclusion (124 +/- 10 versus 145 +/- 32 mumol/l, P < 0.001). CONCLUSIONS: Maintenance CsA monotherapy was effective in 58% of low-immunological-risk first-graft patients and probably did not jeopardize overall results of our first grafts: patient and graft survival were respectively 90 and 73% at 6 years. We propose this policy to avoid long-term complications of glucocorticoid and azathioprine in selected compliant recipients with low immunological risk, follow-up time post-transplantation > 6 months, and stable creatininaemia levels.