Propensity score-based comparison of the graft failure risk between kidney transplant recipients of standard and expanded criteria donor grafts: Toward increasing the pool of marginal donors.

From a prospective and multicentric French cohort, we proposed an external validation study for the expanded criteria donor (ECD), based on 4833 kidney recipients transplanted for the first time between 2000 and 2014. We estimated the subject-specific effect from a multivariable Cox model. We confirmed a 1.75-fold (95% confidence interval [CI] 1.53-2.00, P < .0001) increase in graft failure risk if a given patient received an ECD graft compared to a graft from a donor with standard criteria (standard criteria donor [SCD]). Complementarily, we estimated the population-average effect using propensity scores. We estimated a 1.34-fold (95% CI 1.09-1.64, P = .0049) increase in graft failure risk among ECD patients receiving an ECD graft compared to receiving a SCD graft. With a 10-year follow-up, it corresponded to a decrease of 8 months of the mean time to graft failure due to ECD transplantation (95% CI 2-14 months). The population-average relative risk due to ECD transplantation and the corresponding absolute effect seem finally not so high. Regarding the increase of quality of life in transplantation, our study constitutes an argument to extend the definition of marginality by considering more grafts at high risk and thereby enlarging the pool of kidney grafts.

Treatment Response and Outcomes in Post-transplantation Lymphoproliferative Disease vs Lymphoma in Immunocompetent Patients.

Posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation may carry a poorer prognosis than lymphoma in immunocompetent individuals, but comparative data are lacking. In a retrospective, single-center, case-control study, 21 cases of PTLD were identified in patients undergoing kidney transplantation since 2000, and compared to 42 nontransplanted controls cared for in the same institution and matched for age, prognostic index, and cerebral localization. Two-year and 5-year overall survival was 57% and 44%, respectively, in PTLD patients and 71% and 58% in controls (log-rank test P = .20). On multivariable analysis, overall survival was similar for PTLD and control patients (hazard ratio 1.71, 95% confidence interval 0.81 to 3.61, P = .16). Response rate to first-line chemotherapy was similar between the 2 groups. Death was due to progression of the disease in 46% vs 94% of PTLD and control patients, respectively (P < .01), or sepsis in 31% vs 0% (P = .03). Treatment-related mortality was significantly higher in PTLD (19%) than in controls (0%, P = .03). In conclusion, response to first-line chemotherapy and overall survival are similar in PTLD and control patients, whereas causes of death were significantly different. Better prevention and management of infectious complications could improve the results in PTLD patients.

Early corticosteroid avoidance in kidney transplant recipients receiving ATG-F induction: 5-year actual results of a prospective and randomized study.

One hundred ninety-seven patients received anti-T-lymphocyte globulins Fresenius, mycophenolate mofetil and delayed cyclosporine, and were randomized to ≥6-month corticosteroids (+CS; n=99) or no CS (-CS; n=98). One- and five-year actual graft survival (censored for death) was 93.2% and 86.4% in the +CS group versus 94.9% and 89.8% in the -CS group (5-year follow-up, p=0.487). Freedom from clinical rejection was 86.9% and 81.8% versus 74.5% and 74.5% (p=0.144), respectively, at 1 and 5 years; 5-year freedom from biopsy-proven rejection was 88.9% versus 83.7% (p=0.227). More late first rejections occurred in the +CS group. Significantly lower 5-year graft survival in patients experiencing rejection was observed for +CS (55.6% vs. 92.0%; p=0.005) with 8/18 versus 2/25 graft losses. Renal function at 5 years was stable and comparable (median serum creatinine, 159 vs. 145 µmol/L; creatinine clearance, 53.5 vs. 56.6 mL/min). More +CS patients developed diabetes, dyslipidemia and malignancies. Rejections in -CS patients occurred early after transplantation and did not impair long-term renal function. In patients receiving CS, rejections occurred later and with a higher risk for subsequent graft failure. A similar and not inferior 5-year efficacy profile and a reduced morbidity were observed in CS-free patients compared to patients who received CS for at least 6 months.

An epidemic of Pneumocystis jiroveci pneumonia in a renal transplantation center: role of T-cell lymphopenia.

Although only 2 cases of Pneumocystis jiroveci pneumonia were observed in our center between 2004 and 2009, we diagnosed 9 cases in 2010. Each patient had been in contact in the hospital with at least 1 other patient suffering P jiroveci pneumonia. Genotyping of P jiroveci pneumonia strains demonstrates a total homogeneity of the DNA sequences in the 7 patients already analyzed. CD4+ lymphocyte count was significantly lower at M3 in P jiroveci pneumonia patients than in controls. Our clinical and molecular data confirm that interhuman transmission of P jiroveci is possible, particularly to lymphopenic transplant recipients.

Accuracy of GFR predictive equations in renal transplantation: validation of a new turbidimetric cystatin C assay on Architect c8000.

OBJECTIVES: To evaluate the Sentinel-PETIA cystatin C on Architect c8000 analyzer. DESIGN AND METHODS: We assessed analytical performances and clinical relevance by comparison with a reference isotopic method in kidney transplant recipients. RESULTS: This assay exhibited reliable precision and was close to the non standardized Siemens-PENIA method. All tested equations allowed reliable assessment of GFR. CONCLUSIONS: Cystatin C improved GFR determination at the critical level of 60 mL/min/1.73 m². New formulas might be necessary after IFCC standardization.

Renal transplantation in patients with AA amyloidosis nephropathy: results from a French multicenter study.

Although end-stage renal disease related to AA amyloidosis nephropathy is well characterized, there are limited data concerning patient and graft outcome after renal transplantation. We performed a multicentric retrospective survey to assess the graft and patient survival in 59 renal recipients with AA amyloidosis. The recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall, 5- and 10-year patient survival was significantly lower for the AA amyloidosis patients than for a control group of 177 renal transplant recipients (p = 0.0001, 0.028 and 0.013, respectively). In contrast, we did not observe any statistical differences in the 5- and 10- year graft survival censored for death between two groups. AA amyloidosis-transplanted patients exhibited a high proportion of infectious complications after transplantation (73.2%). Causes of death included both acute cardiovascular events and fatal septic complications. Multivariate analysis demonstrated that the recurrence of AA amyloidosis on the graft (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1-year increase = 1.06, p = 0.03) were significantly associated with risk of death. Finally, patients with AA amyloidosis nephropathy are eligible for renal transplantation but require careful management of both cardiovascular and infectious complications to reduce the high risk of mortality.

Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients.

BACKGROUND: BK polyomavirus virus (BKV) nephropathy (BKVN) is the most common viral infection that affects renal allografts. Because a specific antiviral therapy is lacking, BKVN may result in graft dysfunction and/or loss. We prospectively analyzed whether monthly nucleic acid testing (NAT) for BKV replication in blood and immediate reduction of immunosuppression (IS) could prevent BKVN. METHODS: NAT was performed at monthly intervals for 6 months and then at 12 months in 119 de novo renal transplant recipients. In viremic patients (presumptive BKVN), a graft biopsy was systematically performed and IS was immediately reduced. RESULTS: BKV viremia occurred in 13 (10.9%) patients after a median time of 90 days (23-241); 77% of patients were viremic before month 4. After reduction of IS, viral load was undetectable in 11 patients, remained low in 1, and continued to increase in 1 patient who developed definitive BKVN despite reduction of IS, and finally returned to dialysis 6 months after transplantation. CONCLUSION: BKV infection is an early complication. Monthly NAT in blood during the first 6 months and immediate reduction of IS in viremic patients almost completely prevent definitive BKVN.

Evolution of coronary artery calcifications following kidney transplantation: relationship with osteoprotegerin levels.

We prospectively assessed the evolution of coronary artery calcification (CAC) and osteoprotegerin (OPG) levels after renal transplantation (RT). Eighty-three recipients were followed-up prospectively during 1 year. Blood was collected before (baseline) and after RT for determination of mineral metabolism parameters including OPG. CAC was measured by multidetector computed tomography at transplantation (baseline) and 1 year later. Progression of CAC was defined as a difference between the follow-up square-root transformed volume (SRV) and the baseline SRV >or= 2.5. By multivariate analysis, baseline OPG level, age and low LDL levels were significantly associated with baseline CAC. RT was accompanied by mineral metabolism improvement with a decrease of OPG from 955 [395-5652] to 527 [217-1818] pg/mL and parathyroid hormone from 94 [1-550] to 62 [16-410] pg/mL. Thirty-one percent of patients did not exhibit CAC at baseline. CAC diminished in 14.5%, stabilized in 59.2% and progressed in 26.3% of patients. Baseline CAC was associated with progression (OR 2.92 [1.02-8.36]). No significant association was found between OPG and CAC progression despite a higher baseline OPG level in progressors (1046 [456-3285]) vs. non-progressors (899 [396-5952] pg/mL). CAC at baseline, but not 1 year after RT, is independently associated with baseline OPG; posttransplant CAC progression is predicted by baseline CAC score.

Return to dialysis after renal allograft loss: is dialysis treatment initiated too late?

INTRODUCTION: Allograft failure is a common complication after renal transplantation. However, data describing the level of renal function and the clinical condition of patients returning to dialysis after graft failure are scarce. The purpose of this analysis was to retrospectively determine the stage of end-stage renal failure at dialysis initiation and the outcome during the first year of dialysis among patients who lost their grafts. METHODS: We analyzed deaths with a functioning graft and graft losses among patients transplanted in our center between January 1, 1994, and December 31, 2003. Weight, blood pressure, serum albumin, hemoglobin, phosphorus-calcium levels, and vascular access for dialysis were analyzed at the beginning (D(0)) and at 1 year after initiation of dialysis (M(12)). Creatinine clearance (CrCl), and hemoglobin were also studied at 3 months before beginning renal replacement therapy (M(-3)). RESULTS: Ninety-eight patients lost their grafts after a mean follow-up of 94 +/- 34 months; 37 died with a functioning graft and 61 returned to dialysis. Patient age was 62 +/- 10 years for the first group and 47 +/- 13 years for the second. At D(0), patients were hypertensive and anemic with a mean CrCl of 10 +/- 3 mL/min, suggesting that they were referred too late for dialysis. Surprisingly, at M(-3), CrCl was 19 +/- 7 mL/min and hemoglobin 10.6 +/- 3.6 g/dL. Four patients died during the first year of dialysis. CONCLUSIONS: Our data suggest that transplant patients returned to dialysis too late. CrCl and hemoglobin deteriorate rapidly during the 3 months preceding dialysis initiation.

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

New onset dyslipidemia after renal transplantation: is there a difference between tacrolimus and cyclosporine?

UNLABELLED: Lipid abnormalities including increased total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) have been frequently reported in renal transplantation and could be involved in the high frequency of cardiovascular diseases in this population. PATIENTS AND METHODS: Two hundred ninety-five patients were transplanted between January 1995 and October 2000 in our center. Two hundred two patients were included in this study. Seventy-six patients received tacrolimus (Tac), and 126 patients cyclosporine (CsA). Lipid parameters were assessed the day of transplantation and 1 year posttransplantation. RESULTS: Serum lipids were similar between the two groups at D0. At M12, TC and LDL-C were significantly higher in the CsA group (6.14 +/- 1.37 vs 5.28 +/- 1.32 mmol/L; P < .05 and 3.98 +/- 1.05 vs 3.26 +/- 1.03 mmol/L; P < .05 CsA vs Tac, respectively). TG were comparable in both groups (1.86 +/- 1.07 vs 1.62 +/- 0.92 mmol/L; P = .55; CsA vs Tac). Incidence of de novo hypercholesterolemia was significantly higher in the CsA group (28 vs 8%) whereas incidence of hyperTG was similar in both groups. Prevalence of LDL-C was significantly higher in the CsA group (65% vs 31%; P < .001), whereas there was no difference in high density lipoprotein (HDL)-C levels. DISCUSSION: Mean serum lipid levels and incidence and prevalence of hyperTC, especially LDL-C, was significantly higher in patients receiving CsA when compared with Tac. TG and HDL-C levels were similar. Although the study was retrospective, our results confirm that CsA increases lipid levels, whereas Tac does not. CONCLUSION: Lipid disorders are frequently observed in renal transplant recipients. CsA, but not Tac, significantly increases incidence and prevalence of high TC and LDL-C.

Small dense low-density lipoprotein in renal transplant recipients: a potential target for prevention of cardiovascular complications?

BACKGROUND: Immunosuppressive therapy is frequently associated with dyslipidemia, which is involved in cardiovascular morbidity and mortality in transplant patients. Beyond classical factors, such as low-density lipoprotein (LDL) cholesterol (LDL-C), qualitative abnormalities of lipoproteins, such as presence of the atherogenic factor, small dense LDL, may be of interest for a cardiovascular risk assessment. This study was designed to explore LDL size in renal transplant recipients in relation to quantitative lipid parameters and apolipoprotein (apo) CIII polymorphism. METHODS: Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, apoA1, apoB, apoCIII, and LDL size were measured in 62 patients of mean age 45 +/- 13 years including 71% men at 2 +/- 0.5 years after renal transplantation. Thirty-two patients received cyclosporine (CsA), while 30 received tacrolimus (FK). ApoCIII Sstl genotype was determined by restriction fragment length polymorphism. RESULTS: The CsA group exhibited higher TC (P = .001), LDL-C (P = .004), non-HDL-C (P = .009), HDL-C (P = .03), apoB (P = .008), and apoCIII (P = .002) levels than the FK group. However, LDL-C (CsA: 3.7 +/- 1.2, FK: 3.0 +/- 0.6 mmol/L) and triglyceride levels (CsA: 1.55 mmol/L, FK: 1.37 mmol/L) were near the normal range in both groups. Allelic frequency of the sparse A2 allele associated with hypertriglyceridemia was 6%, similar to the general population. LDL size, which was comparable in the CsA and FK groups (25.87 +/- 0.89 vs 25.75 +/- 0.62 nm, respectively), inversely correlated with TG/HDL ratio (P = 10(-4)). Prevalence of small dense LDL (defined as <25.5 nm) was 26% in the CsA group and 33% in the FK group. CONCLUSION: After LDL-C goal has been achieved, LDL size modulation may be taken into account in order to prevent cardiovascular complications.

Renal transplantation decreases osteoprotegerin levels.

Vascular calcifications are an important risk factor for cardiovascular mortality and morbidity in patients with chronic renal failure. Osteoprotegerin, a soluble decoy receptor for receptor activator NFkB ligand, has emerged as an independent predictive factor of atherosclerosis and vascular calcification in hemodialysis patients. Sparse data are available on the evolution of osteoprotegerin after renal transplantation. The aim of this study was to follow the evolution of serum osteoprotegerin levels and biochemical risk factors after renal transplantation. Forty patients were included. Blood samples for analysis were collected before and 3 months after renal transplantation. Besides the expected diminution in calcium-phosphate product, we have shown an early normalization of osteoprotegerin (10.05 +/- 4.77 pmol/L to 4.59 +/- 2.26 pmol/L). This study demonstrates that kidney transplantation improves this risk factor for vascular calcifications. However, these preliminary results should be confirmed and extended by the follow-up of vascular calcifications in the long term.

Evaluation of an immunoassay (Abbott-IMX Analyzer) allowing routine determination of sirolimus: comparison with LC-MS method.

BACKGROUND: The use of the immunosuppressive agent sirolimus is increasing in renal transplantation but its monitoring often requires high-performance liquid chromatography (HPLC) with ultra-violet (UV) or tandem mass spectrometric (MS-MS) detection. The aim of this study was to compare a new microparticle enzyme immunoassay (MEIA, Microparticle Enzyme Immunoassay) on IMx Abbott Analyser with a liquid chromatography-mass spectometry (LC-MS) method. METHOD: The accuracy of immunoassay analytical performance including within run and between run imprecision and linearity was tested. For comparison studies, sirolimus level was then determined with the two methods on 98 samples from 52 transplant patients. RESULTS: Total intra-assay and inter-assay variation coefficients were below 10% at the three levels tested, and the coefficient of linearity was r = 0.99. The values obtained were highly correlated with the LC-MS method (MEIA = 1.02LC-MS + 0.91; r(2) = 0.87). As a result, the immunoassay showed good performance, and clinical sample measurements were not affected by the method. The MEIA may be a useful alternative for routine monitoring of sirolimus.

Impact of early or delayed cyclosporine on delayed graft function in renal transplant recipients: a randomized, multicenter study.

The benefit of delayed cyclosporine in reducing risk of delayed graft function (DGF) is not clearly established. This study compared early vs. delayed cyclosporine microemulsion (CsA-ME) inde novorenal transplant patients. Patients were randomized to early (day 0, n=97) or delayed (day 6, n=100) CsA-ME at an initial dose of 8 mg/kg/day with dose adjusted according to C2 level. All patients received enteric-coated mycophenolate sodium (EC-MPS), steroids and an anti-interleukin-2 receptor antibody. In both groups, 33% of patients were at high risk of DGF; 26 patients (26.8%) in the early CsA-ME group and 23 patients (23.0%) in the delayed CsA-ME group experienced DGF (n.s.). Renal function at 3 months was comparable (creatinine clearance 51.1 mL/min with early CsA-ME and 53.8 mL/min with delayed CsA-ME), and remained similar to 12 months. Treatment failure, defined as biopsy-proven acute rejection, graft loss or death, did not differ significantly at 12 months (23.7% with early CsA-ME vs. 29.0% with delayed CsA-ME). Biopsy-proven acute rejection occurred in 15.5% of early CsA-ME and 26.5% of delayed CsA-ME patients (n.s.). Both regimens were well tolerated. These data suggest that early or delayed introduction of CsA-ME results in similar renal function in renal transplant patients regardless of DGF risk level.

Sirolimus-associated acute respiratory distress syndrome in a renal transplant recipient.

Sirolimus is a new potent immunosuppressive drug used in organ transplantation; its major advantage is the absence of deterioration in renal function. Documented adverse effects include myelosuppression and hyperlipidemia. Recently several cases of sirolimus-associated interstitial pneumonitis have been reported, usually of mild severity. We report a new case that was complicated by a severe acute respiratory distress syndrome, which required several days of mechanical ventilation. No infectious or cardiogenic etiology was documented. Low sirolimus blood levels and acute CD4 lymphocytic alveolitis suggested an immune-related mechanism rather than a direct toxic effect of the drug. The patient recovered after discontinuation of sirolimus and the administration of corticosteroids.

The V-twin system (Dade Behring Laboratories): a useful tool for immunosuppressive drug monitoring.

The predose trough cyclosporine (CsA) level (C0) was widely used to assess the possibility of drug nephrotoxicity. Owing to its potential limitation as an indicator of total drug exposure, 2-hour postdose (C2) monitoring has been considered to be a more accurate marker. The V-Twin analyzer (Vital SC, Netherlands) conceived for EMIT technologies (Dade Behring Laboratories) is proposed herein to determine CsA levels using a specific calibrator without any dilution, as well as tacrolimus (FK) and mycophenolate mofetil (MMF) levels. Both CsA (C0: n = 133 and C2: n = 55) and FK (n = 121) EMIT assays were compared to the RIA CsA assay (DiaSorin Laboratory) and to the MEIA tacrolimus assay (Abbott Laboratory), respectively. In addition, the feasibility of MMF EMIT assay was evaluated. Overall, 309 transplant patients were included in this study. For all parameters tested, total imprecision studies were lower than 10%, and the coefficient of linearity was r(2) > .99. For the CsA kit, the range of linearity was between 25 and 500 ng/mL for the C0 and 400 and 2000 ng/mL for the C2 assay. The values obtained were highly correlated with the RIA for the C0 levels (EMIT = 0.9 RIA+3.66; r = .97) and for the C2 levels (EMIT = 0.89 RIA-14.2; r = .956). Similar results were obtained with the EK EMIT kit, with a linearity range between 3 and 30 ng/mL, and a high concordance with the MEIA test (EMIT = 0.98 RIA+1.09; r = .96). Preliminary MMF results in 59 sera, containing from 0.1 to 30 microg/mL, showed that this examination could be included as a routine. The V-twin system is a useful tool for routine monitoring with a single method for C0 and C2 cyclosporine, tacrolimus, and mycophenolate levels.

[Sequential protocols with thymoglobuline and delayed introduction of calcineurin: effects on renal function in renal transplant recipients with non immunological risk and low risk of delayed graft function]. / Protocoles séquentiels avec induction par thymoglobulines et introduction retardée des inhibiteurs de la calcineurine: effets sur la fonction du greffon chez le transplanté rénal sans facteur de risque.

Induction therapy with thymoglobuline significantly decreases the risk of acute rejection, particularly in high immunological risk patients, in combined transplantations and in pediatric renal transplantation. After the introduction of cyclosporin in the 1980's and the recognition of its potential nephrotoxicity, induction therapy with delayed introduction of cyclosporin (sequential protocols) have became very popular in many transplant centers and are now used even in low-immunological risk patients. The aim of the present study was to assess the recovery of renal function in low-immunological risk patients receiving a sequential protocol versus those receiving a calcineurin inhibitor at day 1. Among patients receiving their first transplant in our center between January 1999 and June 2000, we selected 72 recipients with no immunological risk and no risk of delayed graft function (DGF). 35 patients (group I) have received a sequential protocol whereas 37 patients (group II) have received a calcineurin inhibitor (Neoral or prograf) at day 1. We analysed creatinine reduction ratio, 24-hour creatinine excretion on post-transplant day 2, and serum creatinine and creatinine clearance at day 15, 30, 45, 60 and 90 post-transplant. There was no difference between groups concerning demographic, immunological or surgical parameters. The percentage of patients with immediate graft function was similar between the two groups (10 versus 9). The number of patients requiring dialysis in the first post-transplant week was also similar (8/35 versus 6/37). The day serum creatinine reached 200 micromol/l was 15 +/- 11 versus 14 +/- 12 in groups I and II respectively. Serum creatinine and creatinine clearance were similar at all time intervals. CMV disease was significantly higher in the group 1 (42% versus 18.5%; p < 0.005). Our data suggest that in patients with low immunological risk and low-risk of DGF, introduction of calcineurin inhibitors as early as the post-transplant day 1 is not deleterious for renal function recovery. These data should be confirmed by a prospective randomised trial.

[Nocardiosis--is it frequently observed after the introduction of new immunosuppressive agents in renal transplantation?]. / La nocardiose est-elle plus fréquemment observée depuis l'introduction des nouveaux immunosuppresseurs en transplantation rénale?

In our series of 1374 renal transplantations performed between February 1970 and December 2002, we observed 6 cases of infection due to Nocardia asteroides. There were 4 males and 2 females, aged 49.8 +/- 12 years (29 to 63 years). One patient received his first transplantation and the 5 others retransplants. Three patients had PRA > 80%, one 28% and one 40%. One patient was diabetic and two had HCV infection. Two of 6 patients experienced acute rejection episodes. Nocardiosis localisation was pulmonary in 5 cases, cerebral in two and mediastinal in one. All patients recovered after reduction of immunosuppression and appropriate antibiotherapy with trimethoprim-sulfamethoxasole (TMP-SMX). When we analyzed the role of immunosuppression, we observed that only two cases were observed in the 933 recipients transplanted between 1985 and 2002 and receiving cyclosporin, contrasting with 4 cases among 174 recipients transplanted between 1996 and 2002 and receiving tacrolimus. Our data suggest that high immunologic risk patients, heavy immunosuppression, and perhaps tacrolimus-based immunosuppression are risk factors of nocardial infection. Early diagnosis of this severe infection, reduction of immunosuppression and appropriate therapy with TMP-SMX resulted in complete recovery in all our patients.