Early Switch to Mammalian Target of Rapamycin Inhibitors Is a Sustainable Treatment Approach in Renal Transplant Recipients: 7-Year Results

ObjectiveThe aim of this study was to investigate the safety and sustainability of mammalian target of rapamycin inhibitor (m-TORi)-based treatment protocols in renal transplant patients.MethodsWe retrospectively evaluated a total of 206 patients who were switched to low-dose calcineurin inhibitors (CNI) + m-TORi or mycophenolate mofetil (MMF) + m-TORi treatment protocols in the first 3 months of renal transplantation between January 2010 and August 2011 in our center. Demographic and laboratory features of the patients were recorded.ResultsOf the patients included in the study, 89 (43.2%) were female and 117 (56.8%) were male. The mean age was 41.9 ± 13.8 years. Panel reactive antibody was negative in 95% of the recipients. One hundred thirty-four (65%) patients received anti-thymocyte globulin induction therapy. Initially, 108 patients were treated with cyclosporine and 98 (47.6%) were treated with tacrolimus-based regimens. One hundred thirty-five patients (65.5%) were switched to low-dose CNI + m-TORi and 71 patients (34.5%) were switched to MMF + m-TORi. The mean switching time was 3 months. At the end of the study, 161 patients (78.2%) were still continuing the m-TORi treatment protocol and 45 patients (21.8%) could not continue for various reasons (11.4% proteinuria, 5.5% edema, 2.9% acute rejection, 1% acne + oral aphthae, 1% neuropathy). The biopsy-proven acute rejection rate was 4.5% (n = 9). The mean duration of sustainability of m-TORi treatment protocol was 84.15 ± 6.79 months. Mean serum creatinine of patients who were still continuing m-TORi was 1.42 ± 1.09 mg/dL.ConclusionSwitching to m-TORi in the early posttransplant period is a safe and sustainable treatment approach.     

Conversion to Everolimus in Kidney Transplant Recipients With Decreased Renal Function

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1–3 mg/d that was sufficient to achieve the recommended levels of 3–8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.     

Variability of the Mammalian Target of Rapamycin Inhibitors Is Correlated With Long-Term Renal Graft Survival

Background

Many studies demonstrate the relationship between the high intrapatient variability of calcineurin inhibitor (CNI) levels and poor long-term renal graft outcome. Our objective is to analyze the intrapatient variability observed in the mammalian target of rapamycin inhibitors (mTOR-i) blood levels, to compare the variability of sirolimus (SRL) with that of everolimus (EVL) in kidney transplant patients converted to an mTOR-i, and to analyze whether the coefficient of variation (CV) was correlated with long-term graft survival.

Mammalian Target of Rapamycin Inhibitor Dyslipidemia in Kidney Transplant Recipients

The incidence, pathogenesis, consequences and treatment of mammalian target of rapamycin (mTOR) inhibitor dyslipidemia are not well described. We conducted a systematic review of randomized controlled trials reporting cholesterol and triglycerides in mTOR versus non-mTOR inhibitor immunosuppressive treatment regimens in kidney transplant recipients. All but one of 17 trials reported higher levels of cholesterol and triglycerides, or an increased prevalence of treatment with lipid-lowering agents. Approximately 60% of mTOR inhibitor-treated patients received lipid-lowering agents (2-fold higher than controls). There appeared to be little difference between dyslipidemias caused by sirolimus (14 trials) versus everolimus (3 trials). It was difficult to determine the extent to which declines in lipids over time posttransplant were due to lipid-lowering therapy, changes in doses and/or discontinuations of mTOR inhibitors. From the four trials that measured lipoproteins, it appeared that at least some of the increase in total cholesterol with mTOR inhibitors was due to increased low-density lipoprotein cholesterol. What direct or indirect effects mTOR inhibitors have on atherosclerotic cardiovascular disease in kidney transplant patients are unknown. However, in the absence of the necessary clinical trials, dyslipidemia should be managed, as it would be in nontransplant patients at high risk for cardiovascular disease.     

Rescue Immunosuppression With Mammalian Target of Rapamycin Inhibitor Drugs in Liver Transplantation

Background

Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants, which have the advantages, with respect to calcineurin inhibitors (CNI; cyclosporine or tacrolimus), of no nephrotoxicity but inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias.

Materials and Methods

Twenty-eight liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 8 hepatocellular carcinomas; 7 de novo malignancies; 6 renal insufficiencies; 3 chronic rejections; 3 acute rejection episodes; and 1 epilepsy.

Results

There were 0% tumor recurrences, 50% improvements in 33% no change, and 17% worsening of renal function among cases of renal insufficiency; 0% improvement in cases of chronic rejection, and 33% improvement in acute rejection episodes. There was a 7% incidence of acute rejection episodes, but no kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. Diarrhea occurred in 7%; hypercholesterolemi in 46% hypertriglyceridemia in 50% thrombocytopenia in 14%, leukopenia in 14%, and anemia in 39%. The 12% intercurrent infection rate included oral thrush in 11%. Lower limb edema occurred in 21%; 1 case displayed facial edema and 1, alopecia.

Conclusions

mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with a low incidence of rejection. Their effectiveness to control steroid-resistant acute rejection episodes or renal insufficiency seems significant, but they are of doubtful benefit for chronic rejection.     

Metabolic and Renal Effects of Mammalian Target of Rapamycin Inhibitors Treatment After Liver Transplantation: Real-Life Single-Center Experience

BackgroundMammalian target of rapamycin (mTOR) inhibitors following liver transplantation (LT) are used to minimize calcineurin inhibitor (CNI)-related nephrotoxicity. Data about metabolic effects of mTOR inhibitors are still limited.AimThis study aims to determine the renal and metabolic effects of different mTOR inhibitor–based protocols in real-life LT patients.MethodsThis is a retrospective cohort study of patients treated with mTOR inhibitors after LT. Demographics, treatment protocols, glomerular filtration rate (GFR), and metabolic parameters were collected over a period of 4 years. Initiation of blood pressure (BP), diabetes mellitus, and lipid medications was also noted.ResultsFifty-two LT recipients received mTOR inhibitors. GFR improved significantly (by 1.96 mL/min/year), with greater improvement in patients with baseline renal dysfunction (+13.3 mL/min vs +4.5 mL/min at 3 years). Conversion to an mTOR inhibitor during the first post-transplant year resulted in a more durable improvement in GFR (for 4 years vs only 1 year for later conversion).No significant weight gain or new-onset diabetes mellitus was observed. However, there was some increase in total cholesterol (+7 mg/dL) and blood pressure (+2 mm Hg during the third year and +8 mm Hg in the fourth years), followed by initiation of lipid-lowering and BP medications in 25% and 13% of patients, respectively.ConclusionsTreatment with an mTOR inhibitor following LT resulted in improved kidney functions without significant negative metabolic effects such as weight gain or new-onset diabetes mellitus. This makes mTOR inhibitors a valuable immunosuppressive option in the face of the growing incidence of nonalcoholic steatohepatitis as a leading cause for LT.     

Improvement of Renal Function After Conversion to Mycophenolate Mofetil Combined With Low-Level Calcineurin Inhibitor in Liver Transplant Recipients With Chronic Renal Dysfunction

Introduction

Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non-nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction.

Patients and Methods

We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 ± 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4-1.7 mg/dL (group I; n = 41); 1.8-2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5-2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria.

Results

Creatinine values after conversion were 1.4 ± 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected.

Conclusion

Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results.     

Liver Transplant Recipients With End-Stage Renal Disease Largely Benefit From Kidney Transplantation

Background

The incidence of end-stage renal disease (ESRD) after liver transplant (LT) has increased. The actual benefit of kidney transplantation (KT) is not completely understood in LT recipients with ESRD.

Immunosuppression With Low-Dose Daclizumab in Liver Transplant Recipients With Impaired Kidney Function: A Single-Center Experience

Background

Nephrotoxicity of calcineurin inhibitors (CNI) may exert detrimental effects, particularly in orthotopic liver transplantation (OLT) patients with impaired kidney function. Immunosuppression with daclizumab permits delayed introduction of CNI, and may be preferred for patients with kidney dysfunction. This retrospective analysis of our experience using daclizumab was performed among patients who underwent transplantation with impaired kidney function.

Methods

We analyzed 168 patients. A serum creatinine (Cr) level >1.5 mg/dL was the indication for a protocol with low-dose daclizumab (50 mg intravenous [IV], day 0 and day 4), mycophenolate mofetil (MMF; 500 mg twice daily IV/orally), and tapering doses of prednisolone from day 0 after OLT. CNI were introduced at day 4-15 after OLT. Patients with a Cr level <1.5 mg/dL received immunosuppression with CNI+MMF+steroids or CNI+steroids.

Results

Fourteen patients fulfilled the criterion for daclizumab immunosupression. Their Cr and creatinine clearance (CrCl) values at OLT were 2.85 ± 1.22 mg/dL and 19 ± 11 mL/min, respectively. In the remaining 154 patients, Cr and CrCl results were 0.88 ± 0.3 mg/dL and 107 ± 82 mL/min, respectively. At discharge, the daclizumab group showed Cr and CrCl estimates of 0.97 ± 0.45 mg/dL and 86 ± 34 mL/min (P < .0001 for both, when compared with prior to OLT). Both Cr and CrCl levels at discharge were not different from those values of patients who underwent transplantation with normal kidney function. The incidence of acuterejection was 14% in the daclizumab group and 18% in the other recipients (P = not significant [NS]).

Conclusions

Immunosuppression with low-dose daclizumab and delayed introduction of CNI was safe and did not increase the risk of an acute rejection episode, thus offerring an excellent therapeutic option for patients who undergo transplantation with impaired kidney function.     

Efficacy, Tolerance, and Safety of Mammalian Target of Rapamycin Inhibitors as Rescue Immunosuppressants in Liver Transplantation

Background

Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants which have the advantages, with respect to calcineurin inhibitors (CNI: cyclosporine or tacrolimus), of no nephrotoxicity and inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias.

Materials and Methods

Twenty-two liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 7 hepatocellular carcinomas; 5 de novo malignancies; 4 renal insufficiencies; 4 chronic rejections; and 2 acute rejection episodes.

Results

There were 16.7% tumor recurrences, and 25% improvements in renal function, 75% in chronic rejection, and 50% in acute rejection. There was no incidence of rejection, kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. We observed incidences of 50% for hypercholesterolemia, 31.8% for hypertriglyceridemia, 22.7% for thrombocytopenia, 18.2% for leukopenia, and 9.1% for anemia. The intercurrent infection rate was 13.6%, including oral thrush in 13.6%. Lower limb edema occurred in 13.6%, with 1 case of facial edema and 1 of alopecia.

Conclusions

mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with no incidence of rejection. Their effectiveness to control chronic rejection seems significant, but it is doubtful for steroid-resistant acute rejection episodes.     

Metabolic Syndrome Is Related to Long-Term Graft Function in Renal Transplant Recipients

The metabolic syndrome (MS) is a known cardiovascular risk factor in the general population and a common problem among renal transplant recipients. This study investigated whether MS after renal transplantation affected long-term graft function.We included 112 transplants at our center between 2000 and 2002. We excluded patients with the presence of pretransplant diabetes or nonstable renal function at 1 year after transplantation. We evaluated parameters such as demographic features, medications, smoking history, body mass index, daily proteinuria, blood pressure, number of HLA mismatches, number of acute rejection episodes, delayed graft function, and laboratory parameters. Patients were followed for a mean of 69.86 ± 21.94 months. The prevalence of MS was determined using the National Cholesterol Education Program—Adult Treatment Panel III criteria.At 1 year after transplant, 28.6% of subjects had MS, whereas only 10.7% had MS before transplantation. Among 27.7% of patients graft failure had occurred during the follow-up; MS was more frequent among these individuals compared with those displaying stable renal function (51.6% vs 19.8%; P = .002). Older donor age, delayed graft function, acute rejection episodes, smoking history, MS, proteinuria, serum creatinine level, and C-reactive protein were associated with graft failure. Upon multivariate Cox regression analysis, patients with MS at 1 year after transplantation showed an increased risk for graft failure (relative risk, 0.22; 95% confidence interval, 0.06-0.75; P = .016). Older donor age and proteinuria level were other independent risk factors for graft failure.The MS was a prominent risk factor for graft failure. Because MS is a cluster of modifiable risk factors, early identification of patients at risk and intervention in due time may improve graft survival.     

Early Withdrawal of Calcineurin Inhibitors and Everolimus Monotherapy in de novo Liver Transplant Recipients Preserves Renal Function

We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novo liver transplantation (LT) patients would result in superior renal function compared to a CsA‐based immunosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy‐eight patients were randomized (Evr n = 52; CsA n = 26). The 1‐year freedom from efficacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p < 0.001). The incidence of CKD stage ≥3 (estimated glomerular filtration rate <60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function, with a similar incidence of rejection and major complications.     

Impaired Renal Allograft Function is Associated with Increased Arterial Stiffness in Renal Transplant Recipients

It is important whether impairment of renal allograft function may deteriorate arterial stiffness in renal transplant recipients. In a cross-sectional study, arterial vascular characteristics were non-invasively determined in 48 patients with renal allograft using applanation tonometry and digital photoplethysmography. Mean age was 51 ± 2 years (mean ± SEM), and studies were performed 17 ± 1 months after transplantation. The stage of chronic kidney disease was based on the glomerular filtration rate. We observed a significant association between the stage of chronic kidney disease and arterial stiffness of large arteries S1 and small arteries S2 in renal transplant recipients (each p < 0.05 by non-parametric Kruskal–Wallis test between groups). Multivariate linear regression analysis showed that male gender of patients with renal allograft (p < 0.01) reduced glomerular filtration rate (p = 0.01), and older age of kidney donor (p = 0.04) were independently associated with an increase of large artery stiffness S1. Furthermore, a significant association between the stage of chronic kidney disease and arterial vascular reactivity during reactive hyperemia was observed (p < 0.05 by non-parametric Kruskal–Wallis test between groups). It is concluded that impairment of renal allograft function is associated with an increased arterial stiffness in renal transplant recipients.     

The Impact of Conversion From Prograf to Generic Tacrolimus in Liver and Kidney Transplant Recipients With Stable Graft Function

Bioequivalence of the recently available generic tacrolimus formulation, manufactured by Sandoz, to the reference product (Prograf; Astellas Pharma, Tokyo, Japan) has been demonstrated in healthy subjects. However, the safety and efficacy of substitution with generic tacrolimus in transplant patients have not been evaluated. Tacrolimus trough concentrations and indices of liver and kidney function were recorded before and after generic substitution in 48 liver and 55 kidney transplant recipients. In liver transplant patients, the mean tacrolimus concentration/dose (C/D) ratio (±SD) was 184.1 (±123.2) ([ng/mL]/[mg/kg/day]) for the reference product and 154.7 (±87.8) ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). The mean C/D‐ratios in kidney transplant patients were 125.3 (±92.7) and 110.4 (±79.2) ([ng/mL]/[mg/kg/day]) for the reference and generic products, respectively (p < 0.05). Actual trough concentrations declined by an average of 1.98 ng/mL in liver and 0.87 ng/mL in kidney transplant patients following the switch, after accounting for all significant covariates. No change was observed in biochemical indices of liver or kidney function and no cases of acute rejection occurred following the substitution. These results suggest that transplant patients currently taking the reference tacrolimus formulation may be safely switched to the Sandoz‐generic product provided trough concentrations are closely monitored following the substitution.     

Adverse Effects of Mammalian Target of Rapamycin Inhibitors During the Postoperative Period After Cardiac Transplantation

Introduction

Safety of treatment with mammalian target of rapamycin inhibitors (mTORi) in the postoperative period after heart transplantation (HT) is controversial.

Methods

We evaluated the incidence of postoperative complications (pericardial, pleural, and surgical wound complications) among nine de novo heart transplant recipients treated with mTORi compared with 19 patients who did not receive them during the same period (control group).

Results

No significant differences were observed between the two groups regarding sex, age, body mass index, pretransplant diagnosis, history of diabetes mellitus, prior cardiac surgery, or baseline renal function. The main laboratory parameters at 1 month were also similar. During the first 2 months after HT, four patients (44%) in the mTORi group developed severe pericardial effusions requiring drainage, compared to 1 (5%) in the control group (P = .026). All patients presenting this complication in the mTORi group received everolimus. In addition, two cases of sternal dehiscence were observed in the mTORi group, compared to none in the control group (P = .09); one patient on everolimus required sternal reopening and debridement for clinically suspected mediastinitis. Duration of chest tube drainage, quantity of collected pleural fluid, and need for thoracentesis were similar in both groups.

Conclusions

In our series, patients receiving mTORi—particularly everolimus—during the postoperative period after HT showed a higher incidence of severe pericardial effusion requiring drainage, as well as a trend toward a higher incidence of sternal dehiscence, as compared to a group not receiving mTORi. The use of mTORi during the early postcardiac transplant period should be individualized.     

Randomized Controlled Trial of Sirolimus Conversion in Cardiac Transplant Recipients With Renal Insufficiency

This randomized, comparative, multinational phase 3b/4 study of patients 1–8 years postcardiac transplantation (mean 3.9 years) evaluated the effect of conversion from a calcineurin inhibitor (CNI) to sirolimus on renal function in patients with renal insufficiency. In total, 116 patients on CNI therapy with GFR 40–90 mL/min/1.73m² were randomized (1:1) to sirolimus (n = 57) or CNI (n = 59). Intent‐to‐treat analysis showed the 1‐year adjusted mean change from baseline in creatinine clearance (Cockcroft‐Gault) was significantly higher with sirolimus versus CNI treatment (+3.0 vs. ?1.4 mL/min/1.73 m², respectively; p = 0.004). By on‐therapy analysis, values were +4.7 and –2.1, respectively (p < 0.001). Acute rejection (AR) rates were numerically higher in the sirolimus group; 1 AR with hemodynamic compromise occurred in each group. A significantly higher treatment discontinuation rate due to adverse events (AEs; 33.3% vs. 0%; p < 0.001) occurred in the sirolimus group. Most common treatment‐emergent AEs significantly higher in the sirolimus group were diarrhea (28.1%), rash (28.1%) and infection (47.4%). Conversion to sirolimus from CNI therapy improved renal function in cardiac transplant recipients with renal impairment, but was associated with an attendant AR risk and higher discontinuation rate attributable to AEs.     

Effect of Rapamycin on Spleen Size in Longstanding Renal Transplant Recipients

Background

Based on evidence available in the literature, rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, but not calcineurin inhibitors (CNIs), has been shown to decrease spleen size. Small spleen, in some instances, is associated with hyposplenism, a condition recently reported in patients with longstanding renal transplant. Accordingly, the effect of immunosuppressive drugs on spleen size was evaluated.

Methods

Renal transplant recipients (35 taking mTOR and 68 CNI) were included, in whom a standardized investigation of the kidney allograft and spleen with the use of color Doppler ultrasound was performed and a peripheral smear were reviewed for the presence of Howell-Jolly bodies (HJBs).

Results

We enrolled 103 patients (64 men; 66 from a deceased donor). The mean age was 47.7 years (range, 23.0–74.0 y). Mean transplant duration was 1,899 days (range, 181–6,883 d). According to the presence of HJBs, the prevalence of hyposplenism was 47.6% for the entire cohort. The differences between the mTOR and CNI groups regarding sex and the presence of HJBs were not statistically significant (P > .05). Age, creatinine, hemoglobin, leukocytes, platelets, and Doppler parameters in spleen and kidney were similar in both groups (P > .05). mTOR patients had a decreased spleen length size (90.09 ± 13.02 mm vs 111.95 ± 18.66 mm; P < .001), a longer transplant duration (3,576 ± 1,594 d vs 1,036 ± 1,369 d; P < .001) and higher serum cholesterol (227.50 ± 38.75 mg/dL vs 182.67 ± 37.74 mg/dL; P < .001) and triglycerides (194.23 ± 79.88 mg/dL vs 148.70 ± 55.54 mg/dL; P = .003) levels compared with the CNI group. A multivariate analysis showed mTOR inhibitor to be the most important predictor of spleen size. In both the mTOR and CNI groups, the comparison between the subgroups of present and absent HJBs did not show any difference.

Conclusions

The findings of this study suggest that small spleens in transplant recipients may be linked to treatment with an mTOR inhibitor, although this apparently does not compromise splenic function.