Posttransplant lymphoproliferative disorders in adult and pediatric renal transplant patients receiving tacrolimus-based immunosuppression

Between March 27, 1989 and December 31, 1997, 1316 kidney transplantations alone were performed under tacrolimus-based immunosuppression at our center. Posttransplant lymphoproliferative disorders (PTLD) developed in 25 (1.9%) cases; the incidence in adults was 1.2% (15/1217), whereas in pediatric patients it was 10.1% (10/99; P<.0001). PTLD was diagnosed 21.0+/-22.5 months after transplantation, 25.0+/-24.7 months in adults and 14.4+/-18.2 months in pediatric patients. Of the 4 adult cases in whom both the donor and recipient Epstein Barr virus (EBV) serologies were known, 2 (50%) were seropositive donor --> seronegative recipient. Of 7 pediatric cases in whom both the donor and recipient EBV serologies were known, 6 (86%) were EBV seropositive donor --> seronegative recipient. Acute rejection was observed before the diagnosis of PTLD in 8 (53%) of 15 adults and 3 (30%) of 10 pediatric patients. Initial treatment of PTLD included a marked decrease or cessation of immunosuppression with concomitant ganciclovir therapy; two adults and two pediatric patients required chemotherapy. With a mean follow-up of 24.9+/-30.1 months after transplantation, the 1- and 5-year actuarial patient and graft survival rates in adults were 93% and 86%, and 80% and 60%, respectively. Two adults died, 3.7 and 46.2 months after transplantation, of complications related to PTLD, and 10 (including the 2 deaths) lost their allograft 3.7-84.7 months after transplantation. In children, the 1- and 5-year actuarial patient and graft survival rates were 100% and 100%, and 100% and 89%, respectively. No child died; one child lost his allograft 41.3 months after transplantation. One child had presumed recurrent PTLD that responded to discontinuation of tacrolimus and reinitiation of antiviral therapy. The mean serum creatinine level in adults was 2.5+/-1.2 mg/dl, and in children, it was 1.3+/-0.6 mg/ dl. Under tacrolimus-based immunosuppression, PTLD is less common after renal transplantation in adults than in children, but PTLD in children is associated with more favorable outcomes than in adults.     

Early renal insufficiency and hospitalized heart disease after renal transplantation in the era of modern immunosuppression

Renal insufficiency has been identified as a risk factor for graft loss and death after renal transplantation but has not been consistently linked to early, nonfatal, hospitalized heart disease (HHD). With the United States Renal Data System database, 29,597 patients who received a kidney transplant between January 1, 1996, and July 31, 2000, with Medicare as the primary payer, and were monitored until December 31, 2000, were studied. Cox proportional-hazards regression models were used to calculate the association of recipient estimated GFR (eGFR) at 1 yr after renal transplantation, as determined with the Modification of Diet in Renal Disease formula, with hospitalization for treatment of acute coronary syndromes (ACS) (International Classification of Diseases, version 9, code 410.x or 411.x) or congestive heart failure (CHF) (code 428.x) 1 to 3 yr after renal transplantation. Rates of ACS and CHF were 2.2 and 4.9%, respectively, for patients with eGFR of <44.8 ml/min per 1.73 m(2), compared with 1.2 and 1.4% for patients with eGFR of >69.7 ml/min per 1.73 m(2). Reduced eGFR (<44.8 ml/min per 1.73 m(2), compared with >69.7 ml/min per 1.73 m(2)) at the end of the first 1 yr after transplantation was independently associated with increased risks of both ACS (adjusted hazard ratio, 2.16; 95% confidence interval, 1.39 to 3.35) and CHF (adjusted hazard ratio, 2.95; 95% confidence interval, 2.24 to 3.90). It was concluded that early renal insufficiency (approximately stage 3 chronic kidney disease) was associated with higher rates of HHD 1 to 3 yr after kidney transplantation. Preservation of renal function after renal transplantation may reduce the rates of HHD, and renal transplant recipients with reduced eGFR should be considered at high risk of developing cardiovascular disease.     

Posttransplant lymphoproliferative disorder in pediatric renal transplantation

Of 84 renal transplants performed in our center since 1986, six recipients (7.1%) developed posttransplant lymphoproliferative disorder (PTLD). All received quadruple immunosuppression with Minnesota anti-lymphoblastic globulin or anti-thymocyte globulin, methylprednisolone, cyclosporine, and azathioprine or mycophenolate mofetil. Five were seronegative for Epstein-Barr virus (EBV) when they received their renal transplant. All patients received prophylactic acyclovir treatment postrenal transplant and none developed a cytomegalovirus (CMV) infection. All patients were positive for EBV by serology and polymerase chain reaction at the time of diagnosis of PTLD. Clinical features at presentation included fever (6/6), adenopathy (4/6), hypertrophied adenoids (4/6), liver involvement (2/6), and allograft involvement (2/6), 2–78 months (4/6<6 months) postrenal transplant. Histopathology of PTLD tissue revealed T cell rich/ Hodgkin disease-like B cell PTLD in one patient, polymorphic PTLD in four, and monomorphic (large B cell lymphoma) PTLD in one. Immunophenotyping of the PTLD biopsy specimen revealed predominant T cells in three, mixed B and T cells in two patients, and B cell in one. No aneuploid populations were identified by flow cytometric DNA ploidy assay. DNA from the PTLD tissue revealed weak to moderate IgH gene rearrangement in four of six patients but no T cell receptor β-chain or c-myc gene rearrangement on Southern blot analysis. The child with monomorphic (large B cell lymphoma) PTLD was clonal with λ light chain restriction on immunophenotyping. Treatment consisted of reduced immunosuppression and ganciclovir/ acyclovir in all patients. CMV hyperimmune globulin was used as an adjunctive therapy in two patients. Chemotherapy was needed in only one patient. A single rejection episode occurred in two children following reduction in immunosuppression, which reversed following intravenous methylprednisolone therapy. PTLD resolved in all patients and at present all patients are alive with functional grafts 2–54 months post diagnosis. Our experience suggests that reduced immunosuppression and anti-viral treatment is adequate in most cases of PTLD, but chemotherapy and hyperimmune globulin therapy may be beneficial in cases resistant to first-line therapy. Since all but one of our patients were EBV seronegative at the time of transplant, vigilance is especially important for early detection of PTLD in this group of the pediatric renal transplant population. Received: 17 November 1998 / Revised: 4 February 1999 / Accepted: 4 February 1999     

Hepatitis C and renal transplantation in the era of modern immunosuppression

Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.     

Post-transplant lymphoproliferative disorders after live donor renal transplantation

The development of post-transplant lymphoproliferative disorders (PTLD) is a well-recognized complication of solid organ transplantation in patients receiving immunosuppressive therapy. The literature on PTLD in live renal allograft recipients is scarce and most of the data pertains to PTLD in cadaveric transplants. As live donor grafts form the mainstay of transplantation programme in India, this study was carried out to define the profile of PTLD in live donor renal allograft recipients. On retrospective evaluation, nine cases of PTLD amongst 1700 live donor allograft recipients from January 1989 to August 2004, were detected at a tertiary care hospital in north India. The clinicopathological features of these cases were evaluated. Mean age at diagnosis of PTLD was 38 yr with median post-transplant latency period of 7 yr. All cases were from extra-renal sites, five being in ileum/jejunum, three in retroperitoneal lymph nodes and one in epididymus. All cases received cyclosporin, azathioprine and prednisolone in varying combinations as immunosuppressive therapy. One case was treated for rejection by anti-thymocyte globulin. Seven patients were seronegative for Epstein-Barr virus at the time of diagnosis. All were B-cell monomorphic PTLD, classifiable as B-cell diffuse large cell lymphomas, with five extranodal and three nodal lymphomas. Management included reduction in immunosuppression, acyclovir therapy, surgical excision and chemotherapy. On follow-up, four patients died, two presented with recurrence, two were in remission and one was lost to follow-up. This study comprising of live related/unrelated renal allograft recipients observed late onset high grade monomorphic PTLD with paucity of early onset polymorphic lesions. Long post-transplant latency period, aggressive behaviour and poor response to treatment necessitate long-term cancer surveillance to facilitate early detection and newer therapeutic strategies to improve the outcome in these patients.     

Posttransplant lymphoproliferative disorders in transplant recipients

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% and 32%. The incidence of PTLD mainly depends on the transplanted organ, the immunosuppressive drugs, the viral serology, and the age of the recipient. The aim of our study was to analyze our patients diagnosed with PTLD. Among 1040 transplantations, including 931 renal, 14 heart, 55 liver and 40 allogeneic peripheral blood stem cell (PBSC), 8 patients (7 male, 1 female) were diagnosed with PTLD. Five patients had undergone renal, one cardiac, one liver, and one PBSC transplantations. Four patients were diagnosed within the first year of transplantation. Six patients presented with abdominal disease, one with convulsions, and one with peripheral lymph node involvement. According to the World Health Organization classification system, six patients were diagnosed as diffuse large B-cell lymphoma, one patient Burkitt's lymphoma, and one polymorphic PTLD. At the time of diagnosis, 7 patients showed positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) Ig G and negative Ig M; one patient, positive EBV Ig M and negative CMV Ig G and M. EBV viral load was extremely high in the plasma of two patients by polymerase chain reaction. One of these patient's pathologic tissue revealed positive EBV DNA, which was not detected in six of the other eight patients. This patient was an 8-year-old boy diagnosed with Burkitt's lymphoma at 31 months after liver transplantation. Seven patients died of disease or complications of chemotherapy. Only one patient survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate was high among our patients with PTLD. To decrease the incidence of PTLD and related mortality, risk factors must be evaluated in multicenter studies.     

Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience

OBJECTIVE: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. METHODS: Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. RESULTS: The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. CONCLUSIONS: While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD.     

Posttransplant lymphoproliferative disorder after umbilical cord blood transplantation in children

Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients received UCBT, including 1 patient who received multiple units and 1 transplanted under nonmyeloablative condition. The time interval from UCBT to PTLD averaged 4 months (range, 2 weeks to 9 months). Patients typically presented with high-stage disease with visceral organ involvement. Histology of the PTLDs showed monomorphic morphology in 5 cases and polymorphic morphology in the remaining 2 cases. Bone marrow biopsies were performed in 3 cases and were negative for PTLD. Epstein-Barr virus (EBV) was detected in the PTLD in all 7 patients by in situ hybridization. Evidence of past EBV infection was found in the recipients, but the EBV genome was not detected in the donor cord blood samples, suggesting that donor cord blood was not the source of EBV infection. The origin of the PTLD was investigated in 5 cases. PTLD was of host origin in 2 patients who failed engraftment and of donor origin in the remaining 3 patients who had complete engraftment. Four of 5 patients with monomorphic PTLD failed to demonstrate significant responses to rituximab and/or reduction of immunosuppression and died within 1 month after diagnosis. The remaining 2 patients with polymorphic PTLD showed complete response to therapy. One patient was alive 35 months after transplant, and the other patient died of infection 6 months after transplant. It is concluded that PTLD arising after UCBT in children occurs early after transplant and represents a serious EBV-related complication. PTLD may be of donor or recipient origin depending on engraftment status. Both monomorphic and polymorphic histology may be seen, and monomorphic histology appears to predict an unfavorable prognosis.     

Posttransplant lymphoproliferative disorder after liver transplantation in miniature swine.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a well-known, life-threatening complication of immunosuppressive therapy, occurring in both adult and pediatric transplant recipients. METHODS: To study the effect of major histocompatibility complex on tolerance induction to primarily vascularized liver allograft, a semi-identical miniature swine model was developed to mimic the clinical situation of parent-into-infant liver transplantation. Long-term acceptance of semi-identical liver allograft was obtained by a transient course of FK506. In a subgroup of six animals, three developed a lethal PTLD. These animals were studied by histology and immunohistochemistry and the anti-donor cellular immune response was assessed. In addition, the possible viral origin of the proliferative process was evoked. RESULTS: Histology and immunohistochemistry revealed an abnormal B-cell proliferation in many organs of swine suffering from PTLD. Evidence of human Epstein-Barr virus, cytomegalovirus, and adenovirus was not evidenced, but a porcine virus responsible for a respiratory and reproductive syndrome (PRRS) was identified in the lymphoid tissue of these animals. In mixed lymphocyte reaction, a significant antiself immune response confirmed an infection by a virus. CONCLUSIONS: This is the first report suggesting that PRRS virus might provoke PTLD in immunosuppressed miniature swine after orthotopic liver transplantation. Whether PTLD could be induced by injection of the PRRS virus in immunosuppressed animals, a pig model of PTLD might be developed and would represent an interesting preclinical model for testing anti-PTLD therapies.     

Posttransplant lymphoproliferative disease after allogeneic transplantation of the spleen in miniature swine

Spleen transplantation (SpTx) was performed in miniature swine across full major histocompatibility complex barriers to study the tolerogenic effect of the spleen. This study describes the development of posttransplant lymphoproliferative disease (PTLD) after allogeneic SpTx. Recipient pigs underwent whole body irradiation (100 cGy), thymic irradiation (700 cGy), and native splenectomy (day 0), and received a 45-day course of intravenous cyclosporine (trough level 400-800 ng/ml). After SpTx, two of seven pigs developed PTLD (1 donor-type, 1 host-type). These two pigs had greater T cell depletion and higher trough levels of cyclosporine. Early changes that occurred prior to the development of clinical features of PTLD were increased porcine lymphotropic herpesvirus-1 viral loads in blood and tissues, and increased numbers of leukocytes, B cells, and total serum IgM. PTLD can occur after allogeneic SpTx in swine. This model may be useful in studies of the pathogenesis of PTLD.     

Hospitalized avascular necrosis after renal transplantation in the United States

BACKGROUND: The national incidence of and risk factors for hospitalized avascular necrosis (AVN) in renal transplant recipients has not been reported. METHODS: This historical cohort study consisted of 42,096 renal transplant recipients enrolled in the United States Renal Data System (USRDS) between 1 July 1994 and 30 June 1998. The data source was USRDS files through May 2000. Associations with hospitalizations for a primary diagnosis of AVN (ICD-9 codes 733.4x) within three years after renal transplant were assessed in an intention-to-treat design by Cox regression analysis. RESULTS: Recipients had a cumulative incidence of 7.1 episodes/1000 person-years from 1994 to 1998. The two-year incidence of AVN did not change significantly over time. Eighty-nine percent of the cases of AVN were due to AVN of the hip (733.42) and 60.2% of patients with AVN underwent total hip arthroplasty (THA); these percentages did not change significantly over time. In the Cox regression analysis, an earlier year of transplant, African American race [adjusted hazard ratio (AHR), 1.65, 95% confidence interval (CI) 1.33 to 2.03], allograft rejection (AHR 1.67, 95% CI 1.35 to 2.07), peritoneal dialysis (vs. hemodialysis; AHR 1.44, 95% CI 1.15 to 1.81), and diabetes (AHR 0.41, 95% CI 0.27 to 0.64) were the only factors independently associated with hospitalizations for AVN. CONCLUSIONS: The incidence of AVN did not decline significantly over time in the renal transplant population. Patients with allograft rejection, African American race, peritoneal dialysis and earlier date of transplant were at the highest risk of AVN, while diabetic recipients were at a decreased risk.     

Hospitalizations for bacterial pneumonia after renal transplantation in the United States

PURPOSE: Bacterial pneumonia has been cited as the leading cause of infectious death in renal transplant recipients but has not been studied in a national transplant population. SUBJECT AND METHODS: Retrospective analysis of the incidence, risk factors and mortality of hospitalized bacterial pneumonia (ICD9 Code 481.x486.x) for 33,479 renal transplant recipients in the United States Renal Data System transplanted from 1 July 1994-30 June 1997. RESULTS: Among all transplant recipients, 4.7% were hospitalized for a primary discharge diagnosis of pneumonia in the study period (2.86 episodes per 100 person years). 9.9% had bronchoscopy and 4.8% had open lung biopsy. A specific etiology was not identified in 72.5% of patients. The hospitalization rate for pneumonia and hazard for mortality due to hospitalized pneumonia were both constant over time. In logistic regression analysis, pneumonia prior to transplant (odds ratio 1.73, 95% confidence interval, 1.32-2.26), older recipient age, diabetes, delayed graft function, rejection (occurring at any time after transplant during the time of the study), duration of pre-transplant dialysis, and positive recipient cytomegalovirus serology were associated with pneumonia. In Cox Regression, hospitalization for pneumonia was associated with greater risk of mortality (hazard ratio 1.64, 95% CI, 1.42-1.89). CONCLUSIONS: Renal transplant recipients with a previous history of pneumonia are at increased risk for subsequent pneumonia, which is associated with substantially decreased patient survival. Given the low rate of specific etiologies identified in this study, invasive diagnosis may be underutilized in this population.     

Posttransplant lymphoproliferative disorders after liver transplantation: analysis of early and late cases in a 255 patient series

We reviewed the incidence and the impact of posttransplant lymphoproliferative disorders (PTLDs) on patient survival among a consecutive series of 255 patients. Five cases of PTLD were observed in adults: two cases were early (less than 1 year) and three cases, late lymphomas. The EBV positivity and the degree of immunosuppression were the main risk factors. We labeled cases as early or late according to whether the time elapsed from the transplant to the first clinical evidence of PTLD was less than 12 months. The median time from transplant to diagnosis of PTLD was 8 (early) and 108 (late) months. All cases were treated by reduction in immunosuppressive therapy with conventional chemotherapy and rituximab. The early cases with lymphoma located at the hepatic hilum died due to local complications (biliary sepsis and hemobilia), after an initial partial response to chemotherapy. The three patients with late cases are in remission after a mean follow-up of 23 months.     

Hospitalizations for bacterial endocarditis after renal transplantation in the United States.

PURPOSE: The national rate of and risk factors for bacterial endocarditis in renal transplant recipients has not been reported. METHODS: Retrospective registry study of 33,479 renal transplant recipients in the United States Renal Data System (USRDS) between 1 July 1994 and 30 June 1997. Hospitalizations for a primary diagnosis of bacterial endocarditis (ICD-9 codes 421.x) within three years after renal transplant were assessed. RESULTS: Renal transplant recipients had an unadjusted incidence ratio for endocarditis of 7.84 (95% confidence interval 4.72-13.25) in 1996. In multivariate analysis, a history of hospitalization for valvular heart disease (adjusted odds ratio (AOR), 25.81, 95% confidence interval 11.28-59.07), graft loss (AOR, 2.81, 95% CI 1.34-5.09), and increased duration of dialysis prior to transplantation were independently associated with hospitalizations for bacterial endocarditis after transplantation. Hospitalization for endocarditis was associated with increased patient mortality in Cox Regression analysis, hazard ratio 4.79, 95% CI 2.97-6.76. CONCLUSIONS: The overall incidence of bacterial endocarditis was much greater in renal transplant recipients than in the general population, although it is still relatively infrequent. Independent risk factors for bacterial endocarditis in the renal transplant recipients were identified, the most significant of which was valvular heart disease. Endocarditis substantially impacts renal transplant recipient survival.     

Hospitalized gastrointestinal bleeding and procedures after renal transplantation in the United States

The risk of hospitalized gastrointestinal bleeding (GIB) in renal transplant recipients has not been studied in a national renal transplant population. Therefore, 42,906 renal transplant recipients in the United States Renal Data System (USRDS) from 1 July 1994 - 30 June 1998 were analyzed in an historical cohort study of hospitalizations with a primary discharge diagnosis of GIB (ICD9 Code 578.9x) using Cox regression analysis. The 1997 National Hospital Discharge Survey was used to obtain rates of GIB for the general population. Renal transplant recipients had a cumulative incidence of hospitalizations for GIB of 334 events/100,000 person-years. In 1997, compared to the general population, renal transplant recipients had an age-adjusted rate ratio for GIB of 10.69 at one year of follow-up. The strongest risk factors for GIB in Cox regression analysis were graft loss (adjusted hazard ratio, 4.28 (2.84-6.47) and African American recipients who experienced allograft rejection (AHR, 3.04, 95% CI, 1.45-6.37). GIB was associated with increased all-cause mortality (hazard ratio 1.78, 95% CI, 1.39-2.28). GIB is significantly more common in renal transplant recipients than in the general population, and the strongest risk factors are graft loss and African Americans who experience rejection.     

Maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the United States

BACKGROUND: Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN. METHODS: By using the U.S. Renal Data System database, we studied 27,772 primary patients on Medicare who received a solitary kidney transplant between January 1, 1996, and July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHRs) for patient- and transplant-related factors (including allograft rejection) with Medicare claims for AVN. The intensity and duration of corticosteroid use could not be assessed. RESULTS: Among patients who were prescribed sirolimus at discharge, 3.5% of patients who received the combination of sirolimus-cyclosporine A (CsA) demonstrated AVN, compared with 1.4% of patients who received the combination of sirolimus-tacrolimus (P=0.06 by chi). In Cox regression, CsA use (vs. tacrolimus) (AHR 1.36, 95% confidence interval, 1.09-1.71) was independently associated with an increased risk of AVN. Sirolimus use showed a trend toward significance (AHR 1.59, 95% confidence interval, 0.99-2.56), with no significant interaction with CsA. CONCLUSIONS: Compared with other maintenance immunosuppression, AVN was significantly more common after use of CsA prescribed at the time of discharge for renal transplantation. Whether this increased risk of AVN was directly attributable to hyperlipidemia, microvascular thrombosis, or differences in corticosteroid dosing could not be determined.     

Graft loss and acute coronary syndromes after renal transplantation in the United States

The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population.