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.     

Mycobacterium Tuberculosis Infection Incidence in Hospitalized Renal Transplant Patients in the United States, 1998–2000

The incidence, risk factors, and prognosis for Mycobacterium tuberculosis (MTB) infection have not been reported in a national population of renal transplant recipients. We performed a retrospective cohort study of 15,870 Medicare patients who received renal transplants from January 1, 1998 to July 31, 2000. Cox regression analysis derived adjusted hazard ratios (AHR) for factors associated with a diagnosis of MTB infection (by Medicare Institutional Claims) and the association of MTB infection with survival. There were 66 renal transplant recipients diagnosed with tuberculosis infection after transplant (2.5 cases per 1000 person years at risk, with some falling off of cases over time). The most common diagnosis was pulmonary TB (41 cases). In Cox regression analysis, only systemic lupus erythematosus (SLE) was independently associated with TB. Mortality after TB was diagnosed was 23% at 1 year, which was significantly higher than in renal transplant recipients without TB (AHR, 4.13, 95% CI, 2.21, 7.71, p < 0.001). Although uncommon, MTB infection is associated with a substantially increased risk of mortality after renal transplantation. High-risk groups, particularly those with SLE prior to transplant, might benefit from intensified screening.     

New-onset gout after kidney transplantation: incidence, risk factors and implications

BACKGROUND: Although cyclosporine use has been associated with an increased risk of new-onset gout after renal transplantation, the incidence and risk factors for new-onset gout have not been reported in the era of modern immunosuppression. METHODS: We conducted a retrospective cohort study of Medicare primary renal transplant patients reported in the United States Renal Data System (USRDS), using Medicare claims data to determine the incidence of new-onset gout. Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for cyclosporine (including separate analysis of Neoral) compared directly with tacrolimus, for the risk of new-onset gout, adjusted for baseline demographic factors and posttransplant renal function. RESULTS: The cumulative incidence of new-onset gout was 7.6% at 3 years posttransplant. The following factors were independently associated with an increased risk of new-onset gout: use of Neoral (vs. tacrolimus, AHR 1.25, 95% CI 1.07-1.47) at discharge, recipient male sex (AHR 1.44, 95% CI 1.25-1.67), older age, higher body mass index, and more recent year of transplant. No other immunosuppressive medications were associated with new-onset gout. Diabetes was associated with a significantly lower risk of new-onset gout. The development of new-onset gout was independently associated with decreased patient survival (AHR 1.26, 95% CI 1.08-1.47) as well as death-censored graft survival. CONCLUSIONS: Cyclosporine is an independent risk factor for new-onset gout after transplantation. The incidence of new-onset gout appears to be increasing even while the use of cyclosporine is decreasing, and the development of new-onset gout was an independent predictor for death and graft loss in this population.     

Impact of diabetes and hepatitis after kidney transplantation on patients who are affected by hepatitis C virus

Complications associated with use of donor hepatitis C-positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (D+/R-, D+/R+, D-/R+ and D-/R-) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in D+/R-, 6.3% in D+/R+, 2.4% in D-/R+, and 0.2% in D-/R-. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in D+/R-, 46.6% in D+/R+, 32.3% in D-/R+, and 25.4% in D-/R-. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCV+ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention.     

Thrombotic microangiopathy in United States long-term dialysis patients.

BACKGROUND: The incidence, risk factors, recurrence rates and prognosis of thrombotic microangiopathy (TMA) among long-term dialysis patients in the United States have not been previously described in a national population. METHODS: 272 024 Medicare primary patients in the United States Renal Data System (USRDS) initiated on end-stage renal disease (ESRD) therapy between 1 April 1995 and 31 December 1999 with Medicare as primary payer were analysed in a retrospective cohort study of USRDS of TMA. Cox regression was used to calculate adjusted hazard ratios (AHR) for risk of TMA and risk of death after TMA. RESULTS: The incidence of TMA in the first year of dialysis was 0.5% overall. Among patients with renal failure due to haemolytic uraemic syndrome (HUS), the incidence of TMA was highest in the first year of dialysis (HUS, 11.3% first year, 4.5% per year thereafter), while among patients without HUS the incidence of TMA was much lower and more constant over time (0.3% per year). In Cox regression analysis, independent risk factors for TMA were renal failure due to HUS (adjusted hazard ratio (AHR) 179, 95% CI 95-338), paediatric age (相似文献   

Gingival overgrowth in renal transplant recipients: a study concerning prevalence, severity, periodontal, and predisposing factors

Gingival overgrowth (GO) is the main oral manifestation in transplant recipients who use calcineurin inhibitors. In the present study, factors for GO development were investigated in Brazilian renal transplant recipients who were prescribed cyclosporine (CsA) or tacrolimus (TAC). Demographic, pharmacological, clinical, and periodontal data were obtained from 83 patients, as well as HLA expression in 51 of them. The prevalence of GO was high (47%), but its severity was low according to periodontal indices. The prevalence of GO was greater among patients who used CsA (n = 49) than those receiving used TAC (n = 34) namely, 61% versus 26.5% (P = .003). Comparisons between patients with versus without GO were performed independent of the administered immunossupressant. The group with GO showed a greater degree of gingival inflammation index. HLA-A68 had greater expression among patients without GO (P = .04). The risk factors for GO occurrence were evaluated using a multivariate analysis that identified gingival inflammation and HLA-A24 expression as risk factors. Increased age and use of TAC were identified as protective factors. GO showed a high prevalence, yet a light intensity. Patients who were younger, men, or received CsA showed a greater occurrence of GO. The risk factors identified for GO development were the presence of gingival inflammation and HLA-A24 expression.     

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.     

Survival after lung transplantation in recipients with alpha‐1‐antitrypsin deficiency compared to other forms of chronic obstructive pulmonary disease: a national cohort study

Alpha‐1‐antitrypsin deficiency (AATD) is grouped with chronic obstructive pulmonary disease (COPD); however, this may not be appropriate. This study assessed whether AATD confers a different prognosis than COPD following lung transplantation. We employed the United Network for Organ Sharing (UNOS) database, grouping patients by diagnoses of AATD or COPD. Kaplan–Meier methods and Cox modeling were performed to determine the association of diagnosis and overall survival. Of 9569 patients, 1394 (14.6%) had a diagnosis of AATD. Patients with AATD who received a single‐lung transplant had reduced 1‐year survival [adjusted hazard ratio (AHR): 1.68, 95% CI: 1.26, 2.23]. Among patients who received a bilateral lung transplant, there was no significant difference in survival by diagnosis (AHR for AATD as compared to COPD: 0.96, 95% CI: 0.82, 1.12). After the implementation of the lung allocation score (LAS), there was no significant difference in survival among patients who received a single (AHR: 1.15, 95% CI: 0.69, 1.95) or bilateral (AHR: 0.99, 95% CI: 0.73, 1.34) lung transplant by diagnosis. Lung transplantation is increasingly employed in the care of the patient with COPD. Although recipients undergoing LTX for AATD are at increased risk of both acute rejection and airway dehiscence post‐transplant, in the post‐LAS era, survival rates are similar for recipients with AATD in comparison with COPD.     

Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression.

To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)-based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 +/- 86.4 ng/mL in recurrent vs. 169.9 +/- 33.3 in tumor-free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral- vs. non-viral-related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha-fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence-free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered.     

A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients

BACKGROUND: Corticosteroids have been a mainstay of rejection prophylaxis for several decades, despite the multiple adverse effects of long-term use, including weight gain, hyperlipidemia, diabetes, hypertension, and bone disease. The detrimental effect of steroids on the metabolic profile begins in the early posttransplantation period, and the complete avoidance of steroids in transplantation would therefore be optimal. We hypothesized that the addition of mycophenolate mofetil (MMF) and a humanized monoclonal anti-CD25 antibody (daclizumab) to a cyclosporine (CsA microemulsion)-based immunosuppression protocol would permit transplantation without steroids. METHODS: Steroid-free renal transplantation was attempted in 57 patients treated with daclizumab, MMF, and CsA. Twenty-eight patients received kidneys from living donors; the remaining 29 received cadaveric grafts. RESULTS: At 1 year, patient and graft survival were 95% and 89%, respectively. Fourteen patients (25%) experienced rejections, of which 13 were readily reversed with steroids; 1 patient required OKT3. Mean serum creatinine at 12 months for patients not experiencing rejection was 149+/-58 micromol/L, compared with 158+/-102 micromol/L for those experiencing rejection. Five patients required hospitalization for infection; no patients developed lymphoproliferative disease. At baseline, 17 patients required 3 or more antihypertensive medications, compared with 2 patients at 1 year. Three of 43 nondiabetic patients developed diabetes during the study. There was no significant reduction in lumbar or femoral bone density. CONCLUSIONS: On the basis of these positive results, we believe steroid avoidance with this immunosuppressive regimen merits further study.     

Arteriovenous fistula use and heart disease in long-term elderly hemodialysis patients: analysis of United States Renal Data System Dialysis Morbidity and Mortality Wave II

BACKGROUND: There are some concerns that arteriovenous fistula (AVF) use or other dialysis specific factors may exacerbate cardiovascular disease in long-term hemodialysis (HD) patients. METHODS: We performed a historical cohort study of the United States Renal Data System Dialysis Morbidity and Mortality Wave II study, limited to 993 patients who started HD in 1996 with valid information on vascular access and who were primarily eligible for Medicare at the start of the study. We assessed the association between hemodialysis vascular access and heart disease, defined as Medicare Claims for heart failure (HF, International Classification of Diseases (ICD9) code 428.x) and acute coronary syndromes (ACS, ICD9 code 410.x and 411.x). Cox proportional hazards regression (using propensity analysis) was used to model adjusted hazard ratios (AHR) for the association between patients factors and heart disease after dialysis. RESULTS: The rate of HF per 100 person years at risk (PYAR) was 19.6 among AVF users, 25.7 among patients using polytetrafluoroethylene grafts (grafts), and 31.1 among patients using temporary catheters. Corresponding rates of ACS were 8.2 among AVF users, 11.0 among users of grafts, and 12.4 among users of temporary catheters. In Cox Regression analysis, there was no significant association between AVF use and either HF or ACS. This lack of association was consistent across gender, diabetes, race, and age. CONCLUSIONS: We found that AVF use had no significant association with the incidence of HF or ACS. We conclude that use of AVF by 60 days after the start of dialysis is not associated with an increased risk of later non-fatal cardiovascular outcomes in long-term hemodialysis patients.     

Charcot neuroarthropathy after simultaneous pancreas–kidney transplantation: risk factors,prevalence, and outcome

We retrospectively analyzed outcome and risk factors of developing Charcot foot (CF) in 100 patients with type 1 diabetes mellitus who underwent a simultaneous pancreas–kidney (SPK) transplantation. Patients who developed CF after SPK transplantation had significantly higher mortality (56% vs. 18%) and more frequently graft failure (44% vs. 13%). Recipients with CF also experienced acute rejections more frequently (78% vs. 41%). They furthermore had higher pre‐transplant values of HbA_1c, received cyclosporine and azathioprine more often, and had significantly higher cumulative corticosteroid use. Patients transplanted in an earlier era (1992–1998) received cyclosporine and azathioprine more often and had a significantly higher cumulative corticosteroid use with the higher prevalence of CF. Conversely, patients with diabetes transplanted more recently (1999–2012) received lower doses of corticosteroids as part of their tacrolimus‐based immunosuppressive therapy, resulting in fewer CF attacks. In conclusion, development of CF after SPK is associated with poor patient and graft outcome. Poor pre‐transplant diabetic control and the use of high‐dose corticosteroids are risk factors for the development of CF. We recommend reduction in or even total avoidance of corticosteroids after SPK transplantation. Given the importance of the diagnosis of CF on outcome, a systematic examination of SPK patients' feet is recommended.     

A comparison of transplant outcomes in peritoneal and hemodialysis patients

BACKGROUND: Studies examining the effect of pre-transplant dialysis modality on graft and patient survival after kidney transplantation have produced conflicting results. Therefore, we studied the effects of pre-transplant dialysis modality on outcomes in a large United States cohort. METHODS: We compared rates of transplantation between peritoneal dialysis and hemodialysis patients from the years 1995 to 1998 in the United States (N = 252,402) and outcomes after transplantation (N = 22,776), using data from the Centers for Medicare and Medicaid Services. RESULTS: In a Cox proportional hazards analysis that was adjusted for multiple patient characteristics, kidney transplantation was 1.39 (95% CI = 1.35 to 1.43) times more likely in peritoneal dialysis vs. hemodialysis patients (P < 0.0001). Over the entire follow-up period, the adjusted risk for death-censored graft failure was 1.15 (1.04 to 1.26) times higher in peritoneal dialysis vs. hemodialysis (P < 0.05), but mortality and overall graft failure rates were not different. Pre-transplant dialysis modality did not affect outcomes for patients who survived with a functioning kidney for at least 3 months. However, in adjusted Cox analyses restricted to the first 3 months, peritoneal dialysis was associated with a 1.23 (1.09 to 1.39) times higher risk for early graft failure (P < 0.001) and a 1.33 (1.16 to 1.53) times higher risk for death-censored graft failure (P < 0.001). Peritoneal dialysis patients, however, were seen to have a lower incidence of delayed graft function. In a smaller sample of patients with data on causes of early graft failure, graft thrombosis was more commonly listed as a cause of graft failure among peritoneal dialysis patients, 41% (64/156), compared to hemodialysis patients, 30% (106/349), P < 0.05. CONCLUSIONS: Kidney transplantation is more frequent in peritoneal dialysis than in hemodialysis patients, and transplantation in peritoneal dialysis patients is more frequently associated with early, but not late, graft failure. Delayed graft function was less common in peritoneal dialysis patients but this potential benefit appears to be offset by other factors which are associated with early graft loss. Additional studies are needed to determine what factors may help understand this early risk of graft failure.     

Multiple drug combinations with "low-dose" cyclosporin for renal transplantation: Multivariate analysis of risk factors determining short-term graft survival within one renal transplant center

Abstract. The factors affecting graft survival in transplant recipients receiving cyclosporin (CsA) are still being debated. Our report is based on an analysis of 202 successive transplantations performed in our institution from May 1984 to December 1986, using low-dose CsA as the basic means of immunosuppression. A total of 142 patients received the triple combination CsA, azathioprine (AZA), and corticosteroids. Sixty patients received a prophylactic combination of CsA, corticosteroids, and antilymphocyte globulins (ALG). From January to December 1986, both regimens were compared in a prospective randomized trial. The factors that affect graft survival were analyzed using the Cox multivariate hazard analysis. The relative risks were calculated for pre-transplant baseline risk factors and for outcome-dependent post-transplant risk factors for surviving grafts at 1 month. Transplants performed with a prolonged ischemia time and patients whose graft did not function immediately were statistically at higher risk of graft loss. Adding prophylactic ALG to CsA was associated with better graft survival. Patients who experienced more than 1 rejection crisis and patients whose 1-month CsA dose was lower than or equal to 5 mg/kg per day were also at significantly higher risk of further graft loss. Neither HLA matching, peak panel reactivity, age of the recipient, occurrence of post-transplant renal dysfunction nor 1-month renal function affected the short-term graft outcome.     

Reduced fracture risk with early corticosteroid withdrawal after kidney transplant

Corticosteroid use after kidney transplantation results in severe bone loss and high fracture risk. Although corticosteroid withdrawal in the early posttransplant period has been associated with bone mass preservation, there are no published data regarding corticosteroid withdrawal and risk of fracture. We hypothesized lower fracture incidence in patients discharged from the hospital without than with corticosteroids after transplantation. From the United States Renal Data System (USRDS), 77, 430 patients were identified who received their first kidney transplant from 2000 to 2006. Fracture incidence leading to hospitalization was determined from 2000 to 2007; discharge immunosuppression was determined from United Networks for Organ Sharing forms. Time-to-event analyses were used to evaluate fracture risk. Median (interquartile range) follow-up was 1448 (808-2061) days. There were 2395 fractures during follow-up; fracture incidence rates were 0.008 and 0.0058 per patient-year for recipients discharged with and without corticosteroid, respectively. Corticosteroid withdrawal was associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59-0.81). Fractures associated with hospitalization are significantly lower with regimens that withdraw corticosteroid. As this study likely underestimates overall fracture incidence, prospective studies are needed to determine differences in overall fracture risk in patients managed with and without corticosteroids after kidney transplantation.     

Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a serious complication of transplantation caused by immunosuppressive drugs. In this study, we assessed the incidence of PTDM and the factors that are associated with the development of this complication. METHODS: The study population included 2078 non-DM renal allograft recipients, transplanted since 1983 in one institution. PTDM was diagnosed by the requirement of hypoglycemic medications, starting more than 30 days after transplantation. Post-transplant, all patients received cyclosporine (CsA) and prednisone, but none of these patients received tacrolimus. RESULTS: At 1, 3, 5, and 10 years after transplantation, 7, 10, 13, and 21% of patients developed PTDM. By multivariate Cox, the following variables correlated with a more rapid increase in the number of PTDM cases: (1) older age (RR = 2.2 comparing patients younger or older than 45 years, P < 0.0001), (2) transplant done after 1995 (RR = 1.7, P = 0.003), (3) African American race (RR = 1.6, P = 0.003), and (4) higher body weight at transplant (RR = 1.4, P < 0.0001). Compared with before 1995, since 1995, the percentage of patients with PTDM has increased from 5.9 to 10.5% at one year and from 8.8 to 16.9% at three years. This increase was statistically independent from all other variables tested. However, since 1995, recipients have become significantly heavier (P < 0.0001) and older (P < 0.0001), and the average CsA level has increased significantly (P < 0.0001). Also, since 1995, the cumulative dose of corticosteroids has declined (P < 0.0001); patients received a newer, better absorbed preparation of CsA and received mycophenolate mofetil. CONCLUSIONS: The risk of PTDM increases continuously with time post-transplant. There has been an increase in the incidence of PTDM in patients transplanted recently, and that increase can be explained only partially by changes in the recipients' characteristics. We postulate that this increase may be due to the introduction of better absorbed CsA formulations that result in higher blood levels and higher cumulative exposure to this diabetogenic drug.     

Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLD) still represent a major preoccupation after renal transplantation, even in the most recent years. METHODS: We analyzed the incidence, risk, and prognostic factors of PTLD in a cohort of kidney recipients using the United States Renal Data System. RESULTS: Among 25,127 Medicare patients transplanted between 1996 and 2000, 344 developed a PTLD defined as a non-Hodgkin lymphoma (1.4%). History of pretransplant malignancy (adjusted hazard ratio [AHR]=3.54, CI 2.31-5.43), younger age (AHR=1.91, CI 1.18-3.1), fewer HLA matches (AHR=1.32, CI 1.1-1.59) and treatment by ATG (AHR=1.55, CI 1.2-1.99) and OKT3 (AHR=1.37, CI 1-1.76), especially if given for rejection therapy were associated with an increased risk of PTLD. Mycophenolate and azathioprine were associated with a lower risk of PTLD (AHR=0.6, CI 0.47-0.78 and AHR=0.66, CI 0.46-0.95, respectively). IL2-receptor inhibitors and sirolimus did not modify the risk of PTLD. Patients without induction therapy treated with tacrolimus were at greater risk of lymphoma than those treated with new formulations of cyclosporine and those treated with antimetabolites (mycophenolate and azathioprine) have a lower risk of PTLD than those without. Patients with PTLD had poor survival (64% vs. 80% at 5 years). Older age, pretransplant malignancy and OKT3 were risk factors for death whereas treatment with mycophenolate was associated with a better survival (AHR=0.49, CI=0.28-0.82). CONCLUSIONS: Our study highlights the contribution of patient history and immunosuppression in the risk of PTLD in the era of modern immunosuppression.     

Hospitalized psychoses after renal transplantation in the United States: incidence,risk factors,and prognosis

Although it is recommended that renal transplant (RT) candidates routinely undergo screening for mental health-related conditions, national statistics for psychoses after RT have not been reported. This is a historical cohort study of 39,628 renal transplant recipients in the United States Renal Data System between July 1, 1994, and June 30, 1998, and followed until December 31, 1999. Adjusted hazard ratios (AHR) for time to hospitalization for both a primary and secondary discharge diagnosis of psychoses (ICD-9 codes 290.x-299.x) after RT and mortality/graft loss after psychosis were assessed by Cox Regression. In addition, rates of psychosis were compared with 178,986 patients with Medicare as their primary payer who started chronic dialysis from April 1, 1995, to June 29, 1999. The incidence of psychoses was 7.5/1000 person-years (PY) after RT compared with 7.2/1000 PY for all patients on chronic dialysis and 9.6/1000 PY for dialysis patients aged 65 yr or younger. Among RT recipients, graft loss (AHR, 2.97; 95% CI, 2.19 to 4.02), allograft rejection, and cadaveric donation were independently associated with psychosis, which was associated with an increased risk of both death (AHR, 2.09; 95% CI, 1.71 to 2.56; P < 0.001) and graft loss (AHR, 1.79; 95% CI, 1.15 to 2.78; P = 0.01). Graft loss due to noncompliance was significantly more common after psychosis (9.0% versus 3.7% in patients not hospitalized for psychosis; P < 0.001). The incidence of hospitalized psychosis was not substantially higher after RT compared with chronic dialysis patients. Psychoses were independently associated with increased risk of death and graft loss after renal transplantation, possibly mediated through medical non-adherence.     

Thrombophilia and avascular necrosis of femoral head in kidney allograft recipients.

BACKGROUND: Thrombophilia has been implicated in the development of avascular necrosis (AVN) in various diseases. We aimed to search for the relation of both prothrombin gene G20210A mutation and factor V G1691A (factor V Leiden) mutation with AVN among kidney transplant recipients. METHODS: Nineteen patients with AVN and 38 control patients without AVN were included. Clinical information was collected, and gender, age, type of renal allograft, duration and type of dialysis, presence of acute rejection, and cumulative doses of ciclosporin and corticosteroid administration were taken into consideration. Genotypes of factor V G1691A and prothrombin G20210A were determined by direct sequencing of genomic DNA. RESULTS: Factor V Leiden mutation was detected in six patients (31.6%) among patients with AVN and in only three patients (7.9%) in the control group (P = 0.048). Two patients (10.5%) in the AVN group were determined to have prothrombin G20210A mutation, while no prothrombin G20210A mutation was detected in the control group. When both of the mutations causing thrombophilia were considered, a total of eight patients (42.1%) in the AVN group and three patients (7.9%) in the control group were identified (P = 0.004). CONCLUSION: Thrombophilia seems to be an important risk factor for development of AVN. More studies are needed to clarify the role of factor V G1691A and prothrombin G20210A mutation for AVN.     

Avascular osteonecrosis after allogeneic hematopoietic stem-cell transplantation: diagnosis and gender matter

BACKGROUND: Avascular osteonecrosis (AVN) is a serious complication of allogeneic stem-cell transplantation (SCT). Acute and chronic graft-versus-host disease and its treatment with steroids are identified as main risk factors. In a single-center, prospective cohort study of patients undergoing allogeneic SCT for chronic myeloid leukemia (CML), acute myeloid leukemia, myelodysplastic syndrome, and acute lymphatic leukemia, we determined the incidence of hip AVN necessitating total arthroplasty (severe adverse event) and performed risk factor analysis. METHODS: A total of 255 patients were followed for an observation period of at least 4 years. Thirteen potential risk factors including age, recipient and donor gender, underlying disease and disease stage, conditioning therapy, human leukocyte antigen match, acute or chronic graft-versus-host disease, and immunosuppressive medication were tested in univariate and multifactorial nominal logistic and Cox proportional hazard analyses. RESULTS: Severe adverse events occurred in eight patients (4-year cumulative incidence rate 6.1%). Univariate and multifactorial analysis revealed a diagnosis other than CML and steroid intake as main risk factors (chi model 31.6, P=0.0005; chi diagnosis 11, P=0.001; chi steroid 6.8, P=0.009). The demonstrably strong influence of diagnosis was steroid independent (steroid intake in CML comparable to non-CML). We repeated the analysis in 103 patients without CML (70 with acute myeloid leukemia, 13 with myelodysplastic syndrome, and 20 with acute lymphatic leukemia), excluding 152 patients with CML. Univariate and multifactorial analyses revealed female gender (of both recipient and donor) as risk factors for AVN in addition to steroids. Relative AVN risk for female compared with male donor transplantation was 8.7 (P=0.01); relative AVN risk for female compared with male recipient transplantation was 4.3 (P=0.047). CONCLUSIONS: Diagnosis and gender are steroid-independent risk factors for severe hip AVN after allogeneic SCT.