The effect of smoking on biliary complications following liver transplantation

We sought to estimate the effect of smoking on the biliary complication rate following orthotopic liver transplantation. We retrospectively evaluated the records of liver transplant recipients at our center from July 1, 1999 to October 26, 2007. Using Cox proportional hazards models, we estimated the time to the earliest biliary complication (leak or stricture) based on smoking exposure, as active, former, or lifetime nonsmoker, adjusting for other clinical factors. Overall, 409 liver transplant recipients were evaluated. The overall biliary complication rate was 37.7% (n = 154). Biliary complications included 66 anastomotic leaks, 60 anastomotic strictures, and 28 nonanastomotic lesions. ERCP was the primary diagnostic modality (n = 112). 18.1% of liver transplant recipients were active smokers (n = 74) and 42.8% were former smokers (n = 175). Active smokers were at greatest risk for biliary complications on unadjusted analysis (P = 0.022). After multivariable adjustment, active smokers had a 92% higher rate of biliary complication rates compared with lifetime nonsmokers (HR 1.92, 95% CI 1.07–3.43), but no difference was noted in the rate of complication resolution. Smoking clearly portends a significant risk of biliary complications following liver transplantation. Smoking status should be clearly defined when evaluating transplant candidacy and in counseling patients with cirrhosis.     

Excess risk of renal allograft loss associated with cigarette smoking.

BACKGROUND: Cigarette smoking contributes to a number of health-related problems, but its impact on renal transplant survival beyond accelerated patient death is unclear. METHODS: We performed a cohort study of 645 adult renal allograft recipients from 1985 to 1995 to evaluate the relationship between smoking and graft outcome. RESULTS: Twenty-four percent of recipients (156/645) were smokers at the time of transplant evaluation. Of these, 90% continued to smoke after transplantation. Pretransplant smoking was significantly associated with reduced overall graft and death-censored graft survival. Patients who were smokers at the time of pretransplant evaluation had kidney graft survival of 84%, 65%, and 48% at 1, 5, and 10 years, respectively, compared with graft survival in nonsmokers of 88%, 78%, and 62% (P=0.007). Pretransplant smoking adversely affected death-censored graft survival in recipients of cadaveric (P=0.02) and of living donor kidneys (P=0.02). Reduced graft survival in pretransplant smokers could not be accounted for by differences in rejection (64% vs. 61%, P=0.35). In a multivariate analysis, pretransplant smoking was associated with a relative risk of 2.3 for graft loss. Among patients with a smoking history before transplantation, death-censored graft survival was significantly higher for those who quit smoking before transplant evaluation. CONCLUSIONS: Cigarette smoking before kidney transplantation contributes significantly to allograft loss. The effect of smoking on graft outcome is not explained by increases in rejection or patient death. Smoking cessation before renal transplantation has beneficial effects on graft survival. These effects should be emphasized to patients with end-stage renal disease who are considering renal transplantation.     

Impact of smoking on progression of vascular diseases and patient survival in type-1 diabetic patients after simultaneous kidney-pancreas transplantation in a single centre.

We evaluated the impact of smoking on the progression of macro-angiopathy as well as patient and graft survival in 35 type-1 diabetic patients with simultaneous kidney-pancreas transplantation (SKPT). According to their smoking history, the patients were divided into smokers (n = 12) and nonsmokers (n = 23). Mean observation period was 80 (12-168) vs. 84 (12-228) months. The prevalence of vascular diseases as well as the incidence of vascular complications during the observation period was evaluated in each group. Graft- and patient survival were calculated. The prevalence of all vascular diseases was higher in the smokers with prior SKPT at the start as also at the end of study; however, the differences were not significant. In addition, the incidence of vascular complications (stroke, myocardial infarction and amputation) during the follow-up period was higher in the smoking group. Taking all vascular complications together (events/patient/year) the difference was significant (0.105 vs. 0.066, P < 0.05). One- and 5-year patient survival was 100% and 75% for smokers vs. 100% and 91% for nonsmokers. One- and 5-year pancreas graft survival at the same time was 100% and 75% in living smokers as well as 100% and 83% in the nonsmokers: We conclude that smoking after SKPT is associated with a progression of macro-angiopathy. Additionally, mortality after SKPT tends to be higher in smoking patients.     

Impact of smoking on progression of vascular diseases and patient survival in type-1 diabetic patients after simultaneous kidney–pancreas transplantation in a single centre

We evaluated the impact of smoking on the progression of macro-angiopathy as well as patient and graft survival in 35 type-1 diabetic patients with simultaneous kidney–pancreas transplantation (SKPT). According to their smoking history, the patients were divided into smokers ( n  = 12) and nonsmokers ( n  = 23). Mean observation period was 80 (12–168) vs. 84 (12–228) months. The prevalence of vascular diseases as well as the incidence of vascular complications during the observation period was evaluated in each group. Graft- and patient survival were calculated. The prevalence of all vascular diseases was higher in the smokers with prior SKPT at the start as also at the end of study; however, the differences were not significant. In addition, the incidence of vascular complications (stroke, myocardial infarction and amputation) during the follow-up period was higher in the smoking group. Taking all vascular complications together (events/patient/year) the difference was significant (0.105 vs. 0.066, P  < 0.05). One- and  5-year patient survival was 100% and 75% for smokers vs. 100% and 91% for nonsmokers.  One- and 5-year pancreas graft survival at the same time was 100% and 75% in living smokers as well as 100% and 83% in the nonsmokers: We conclude that smoking after SKPT is associated with a progression of macro-angiopathy. Additionally, mortality after SKPT tends to be higher in smoking patients.     

Cigarette smoking and chronic allograft nephropathy.

BACKGROUND: Smoking has been demonstrated to decrease patient and graft survival after kidney transplantation. Data on histological changes associated with smoking in renal allografts are lacking. METHODS: Smoking habits before and after renal transplantation were evaluated by questionnaire in 279 patients. A transplant biopsy was performed more than 1 year after transplantation in 76 of them. Histological changes were classified according to Banff 97 criteria. Linear regression analysis and proportional odds models for histological changes including the factors age, gender, diabetes, body mass index, donor age, time since transplantation, history of acute rejection and smoking status were calculated. RESULTS: Overall 22% of patients continued smoking after transplantation, with the proportion decreasing from 38% of those transplanted before 1990 to 13% of those transplanted after 2000. Serum creatinine was non-significantly higher in smokers (2.3 +/- 2.7 mg/dl vs 1.8 +/- 1.4 mg/dl, P = 0.21). A renal biopsy was performed in 24% of non-smokers and 39% of smokers (P = 0.02), and smokers were biopsied on average 1.5 years earlier. Among biopsied patients current smokers tended to suffer more often from diabetes (25.0% vs 13.5%, P = 0.33), to develop transplant failure (33.3% vs 21.2%, P = 0.25) or experience a cardiovascular event (29.2% vs 15.4%, P = 0.16). The frequency of acute rejection was comparable between smokers and non-smokers (25.0% vs 34.6%, P = 0.40). Glomerular sclerosis was associated with diabetes (P = 0.03). Severity of vascular intimal fibrous thickening was associated with current smoking (P = 0.004), whereas the degree of arteriolar hyalinosis (P < 0.001) and chronic/sclerosing nephropathy (P = 0.05) were associated with time since transplantation. CONCLUSIONS: The number of patients who continue cigarette smoking after renal transplantation has decreased in recent years. The main allograft lesion associated with smoking is fibrous intimal thickening of small arteries.     

De novo malignancies and liver transplantation

INTRODUCTION: De novo tumors (DNTs) are the leading cause of late death among liver transplant recipients with an incidence of 5% to 15%, which is significantly greater than the general population. In this retrospective study, we compared this complication in liver transplant recipients to sex- and age-matched controls. PATIENTS: Among 410 patients who received liver allografts between March 1986 and December 2000, 32 (7.8%) developed a DNT. Epidermoid tumors were the most frequent histologic lineage. A complete response was observed in 19 patients (59.4%), a partial response in eight (25%), and no response in five (15%). Survival was lower among liver transplant recipients than controls, a difference that was statistically significant. Treatment consisted of surgery in 76.7%, radiotherapy in 16.7%, chemotherapy in 13.3%, and reduction of immunosuppression in 10%. RESULTS: The mean survival time in transplant patients of 122.97 months (95% CI; range 98-147 months) was significantly shorter than controls, 156.5 months (95% CI; range 141-171 months). About 50% of patients were smokers (active or ex-smokers), compared to 20.7% of controls (P=.049). Significant differences were also found when the three subgroups (smokers, previous smokers, and nonsmokers) were analyzed separately (P=.013). Patients were smokers (active or nonactive) among 45% of cases of skin tumors; 60% of hematological tumors; 71.4% of epidermoids; and 33% of sarcomas. CONCLUSIONS: DNTs, a complication of long-term immunosuppression in patients after liver transplantation, most frequently presented as skin tumors and PTLD. Occurrence of a DNT was an adverse prognostic factor for survival. Smoking represents an independent risk factor for these tumors.     

Analysis of survival after liver transplantation in Galicia, Spain

BACKGROUND: Transplantation is the treatment of choice for many patients with end-stage liver disease. We evaluated the results of liver transplantation in Galicia, an autonomous community in Northwest Spain. METHODS: We analyzed 452 patients and 490 grafts from 1996 to 2000 for causes of loss with respect to recipient and donor variables using the actuarial method, Kaplan-Meier curves, log-rank test, and Cox proportional risks model. RESULTS: The overall graft survival was 77% and 64% at 1 and 5 years, respectively; while that of the patients was 83% and 69%. The risk factors for graft loss were donation in heart failure (HR = 4.91, CI:2.51-9.61); donor age (HR = 1.70, CI:1.01-2.85 between 40 and 60 years; HR = 2.37, CI:1.37-4.10 in those over 60 years, as compared to patients under 40); urgent transplant (HR = 3.95, CI:2.07-7.54); and transplant due to acute liver failure (HR = 3.53, CI:1.72-7.25) as compared to alcoholic cirrhosis. For patient death the risk factors were age of recipient over 60 years, compared to those under 40 (HR = 2.42, CI:1.11-5.28); foreign place of origin (HR = 2.02, CI:1.14-3.59); transplant due to viral cirrhosis (HR = 1.76, CI:1.03-3.02) and transplant due to acute liver failure (HR = 4.62, CI:2.12-10.06), as compared to alcoholic cirrhosis; urgent transplant (HR = 2.65, CI:1.48-4.72), and age of donor over 60 years, as compared to those under 40 (HR = 2.65, CI:1.48-4.72). Infections were the principal cause of death (45%), mostly in the first month (72%); while after the first year, 74% were due to recurrence of the primary disease and de novo malignancy. CONCLUSIONS: Graft and patient survivals were comparable to international registries. The donor characteristics had a greater influence on graft survival than on patient survival.     

Cyclosporine A Protects Against Primary Biliary Cirrhosis Recurrence After Liver Transplantation

Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following liver transplantation (LT). The aims of our study were to evaluate the risk factors associated with PBC recurrence and determine whether recurrent disease constitutes a negative predictor for survival. One hundred and eight patients receiving LT for end‐stage PBC were studied. Recurrent disease was diagnosed in 28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10 years with an overall incidence of 3.97 cases per 100 patient years. By univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44–16.11, p < 0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89–14.33, p = 0.001) were associated with higher risk of recurrence; whereas use of cyclosporine A (CsA) and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI 0.05–0.35, p < 0.001 and HR 0.27, 95% CI 0.11–0.64, p = 0.003, respectively). In the multivariate Cox analysis, only CsA was independently associated with protection against recurrence (HR 0.17, 95% CI 0.06–0.71, p = 0.02). Five‐year probability of survival was 83% and 96%, in patients without and with recurrence (log‐rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a lower risk of disease recurrence, the development of recurrent PBC did not impact on long‐term patient survival.     

Mortality after kidney transplant failure: the impact of non-immunologic factors

BACKGROUND: One third of cadaveric kidney transplant recipients suffer graft loss within five years of transplantation. Non-immunologic factors that predict mortality among non-transplant patients also may be potentially modifiable risk factors for mortality among patients with transplant failure. METHODS: Applying multivariate survival analysis to data from the United States Renal Data System, we determined the effect of immunologic or transplant related factors and non-immunologic factors on mortality in patients who initiated dialysis after kidney transplant failure in the United States between April 1995 and September 1998. RESULTS: A total of 4741 patients were followed for a median +/- standard deviation of 15 +/- 11 months after initiation of dialysis after transplant failure. The majority of the 1016 (21%) deaths were due to cardiac (36%) or infectious (17%) causes. Patients in the following groups had an increased risk for all-cause mortality: older patients [hazard ratio (HR) = 1.04 per year, 95% confidence interval (95% CI) 1.03-1.04], women (HR = 1.31, 95% CI 1.10-1.56), patients of white race (HR = 1.94, 95% CI 1.32-2.84), patients with diabetes (HR = 1.76, 95% CI 1.43-2.16), peripheral vascular disease (HR = 1.94, 95% CI 1.54-2.43), congestive heart failure (HR = 1.26, 95% CI 1.05-1.53), drug use (HR = 2.23; 95% CI 1.08-4.60), smokers (HR = 1.35, 95% CI 1.01-1.81), first transplant recipients (HR = 1.32, 95% CI 1.02-1.69), and patients with a higher glomerular filtration rate (GFR) at dialysis initiation (HR = 1.04 per mL/min higher, 95% CI 1.02-1.06). Those with private insurance (HR = 0.67, 95% CI 0.49-0.93) and higher serum albumin (HR = 0.73 per g/dL higher, 95% CI 0.64-0.83) had a decreased risk for all-cause mortality. Acute rejection, antibody induction, donor source, duration of graft survival and the maximum attained GFR during transplantation did not predict all-cause mortality. CONCLUSIONS: Non-immunologic factors predicted mortality among patients with transplant failure but immunologic and transplant related factors did not. Prevention, early diagnosis and treatment of co-morbid conditions and the complications of chronic kidney disease may improve the survival of patients with transplant failure.     

Impact of Microsurgical Anastomosis of Hepatic Artery on Arterial Complications and Survival Outcomes After Liver Transplantation

Hepatic artery (HA) complications after liver transplant (LT) can lead to biliary complications, graft failure, and mortality. Although microsurgery has been established to improve anastomotic outcomes, it prolongs surgical time and has not reached widespread adoption at all transplant centers. We investigated the incidences of arterial, biliary complications and outcomes after using microsurgery to anastomose HA during LT. Retrospective cohort of consecutive LT performed from 2006 to 2018 was reviewed for operative details and postoperative outcomes. Cox-regression models were used to investigate the relationship between variables and outcomes. Eighty (62.5%) LTs (Group 1) were performed without and compared with 48 (Group 2) with microsurgical anastomosis of HA. Both groups were comparable in terms of arterial and biliary anastomoses performed. Incidence of early HA thrombosis was similar (6.2% vs 2.1%, P = .28). Group 2 had lower incidence of short- and long-term arterial complications, especially amongst living donor liver transplantations (LDLT) (5.3% vs 35.0%, P = .022). On multivariate analysis, microsurgery was associated with lower risk (hazard ratio [HR] 0.09, 95% confidence interval [CI] 0.01-0.71) of, and LDLT had higher risk (HR 4.23, 95% CI 1.46-12.27) of arterial complications. Biliary complications were associated with LDLT (HR 3.91, 95% CI 1.30-11.71) and dual biliary anastomoses (HR 5.26, 95% CI 1.15-24.08) but not with occurrence of HA complications. Worse patient survival was associated with the occurrence of any HA complication (HR 4.11, 95% CI 1.78-9.48). Hepatic arterial complications can be reduced using microsurgical techniques for the anastomosis, resulting in improved patient survival outcomes after liver transplantation.     

Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation.

With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994-1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P=0.008), donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P=0.004), and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P=0.003) were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P=0.003) and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P=0.03) were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients.     

Risk factors for smoking abuse after heart transplantation

Patients (n = 103) were studied before heart transplantation with regard to smoking habits by means of a clinical interview, and 81 were submitted to Minnesota Multiphasic Personality Inventory (MMPI). After a mean time of 50.8 +/- 24.2 months from transplant, they were once again interviewed to ascertain their smoking habits after intervention. Nonsmokers (35 of 103) were still nonabusers. Of the remaining 68 patients who ceased smoking before heart transplant, 12 (17.6%) had returned to tobacco abuse. Dividing these 68 patients into two groups based upon the length of smoking cessation before heart transplant (less than 1 year: short term [ST] more than 1 year: long term [LT]), we noticed that the ST group showed a much greater rate of reabuse (8 of 20, 40%) than the LT group (4 of 48, 8.3%, P =.006). Analyzing six scales of MMPI, we found a statistically different score for self-control ability (scale K) in ST and LT smokers compared to nonsmokers (45.5 and 45.5 vs 51.2, P =.026), and for difficult adaptation (scale Ma) in ST compared both to LT smokers and nonsmokers (ST 57, LT 50.5, NS 47.6; P =.042 LT vs ST, P =.0005 ST vs NS). We concluded that patients who have recently decided to stop smoking and show after MMPI compilation a score of >50 for K and <50 for Ma scale have a higher risk of reabuse and need a greater effort by the transplant team to reinforce their will to stop smoking.     

Dynamic changes in MELD score not only predict survival on the waiting list but also overall survival after liver transplantation

The predictive value of MELD score for post‐transplant survival has been under constant debate since its implementation in 2001. Aim of this study was to assess the impact of alterations in MELD score throughout waiting time (WT) on post‐transplant survival. A single‐centre retrospective analysis of 1125 consecutive patients listed for liver transplantation between 1997 and 2009 was performed. The impact of MELD score and dynamic changes in MELD score (DeltaMELD), as well as age, sex, year of listing and WT were evaluated on waiting list mortality and post‐transplant survival. In this cohort, 539 (60%) patients were transplanted, 223 (25%) died on list and 142 (15%) were removed from the waiting list during WT. One‐, three‐ and five‐year survival after liver transplantation were 83%, 78% and 76% respectively. DeltaMELD as a continuous variable proved to be the only significant risk factor for overall survival after liver transplantation (hazard ratio (HR): 1.06, 95% confidence interval (CI) 1.02–1.1, P = 0.013). The highest risk of post‐transplant death could be defined for patients with a DeltaMELD > 10 (HR: 4.87, 95% CI 2.09–11.35, P < 0.0001). In addition, DeltaMELD as well as MELD at listing showed a significant impact on waiting list mortality. DeltaMELD may provide an easy evaluation tool to identify patients on the liver transplant waiting list with a high mortality risk after transplantation in the current setting. Temporarily withholding and re‐evaluating these patients might improve overall outcome after liver transplantation.     

Impact of smoking on survival after heart transplantation

INTRODUCTION: Smoking is an important risk factor in any population group. According to previous studies, having been a smoker before heart transplantation (HT) confers a greater likelihood of developing any type of tumor or other complication after HT. Our objective was to determine the impact of having been a smoker before HT on survival, respiratory complications during the postoperative period, and long-term tumor development. MATERIALS AND METHODS: After excluding combined transplantations, pediatric transplantations, and retransplantations, we retrospectively reviewed 288 HT performed between November 1987 and September 2006. We divided patients into nonsmokers (including those who quit smoking more than 1 year before HT (n = 163), exsmokers for less than 1 year (n = 76), and those who smoked until HT (n = 49). The statistical tests were chi-square, Student t, analysis of variance (ANOVA), and Kaplan-Meier curves. RESULTS: There were more male patients among smokers and exsmokers than nonsmokers (93.9% vs 96.1% vs 82%, respectively; P = .003). There were no differences in baseline characteristics between the groups. Exsmokers remained intubated for a longer time than smokers or nonsmokers (33.4 +/- 44.6 vs 14.2 +/- 7.3 vs 17.9 +/- 19.2, respectively; P = .05). We observed the same trend in recovery unit stay (7.9 +/- 10.5 days vs 4.4 +/- 1.88 days vs 4.84 +/- 3.49 days, respectively; P = .021). The development of any type of tumor was also more frequent among smokers and exsmokers, although not significantly. The survival rate was similar in nonsmokers and exsmokers, although higher than in smokers (89.57 vs 92.11% vs 81.63%, respectively; P = .031). We did not observe differences in the causes of death. CONCLUSIONS: Patients who smoke or have smoked until shortly before HT showed a poorer prognosis and a longer recovery unit stay. There was also a trend to increased tumor development.     

Modifiable factors predicting patient survival in elderly kidney transplant recipients

BACKGROUND: Elderly transplant candidates represent an increasingly important group on the waiting list for kidney transplantation. Yet the factors that determine posttransplantation outcomes in this population remain poorly defined. METHODS: We performed a population-based retrospective cohort study involving all patients aged 60 years or older who received a first cadaveric kidney transplantation between 1985 and 2000 in the province of Quebec. The main outcomes were patient survival, overall graft survival, and treatment failure (patient death or graft loss within the first posttransplant year). Survival analyses were performed using a Cox proportional hazard model. Logistic regression identified factors predicting treatment failure. RESULTS: On multivariate analysis, the modifiable factors associated with patient survival were active smoking at transplantation [hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.22-3.60)], body mass index (BMI) (HR 1.34 for a 5-point increase, 95% CI 1.05-1.67), and time on dialysis before transplantation (HR 1.10 for a 1-year increase, 95% CI 1.02-1.18). The only modifiable factor associated with graft survival was active smoking at transplantation (HR 2.04, 95% CI 1.24-3.30). Treatment failure was associated with time on dialysis before transplantation (odds ratio for dialysis >/=2 years 3.28, 95% CI 1.34-7.9). CONCLUSION: Our results show that active smoking, obesity, and time on dialysis before transplantation are modifiable risk factors associated with an increased risk of mortality after transplantation in elderly recipients. They represent potential targets for interventions aimed at improving patient and graft survival in elderly patients.     

Cigarette smoking in renal transplant recipients

Cigarette smoking may adversely influence patient and graft survival. In Europe and the United States the prevalence of cigarette smoking in dialysis patients is 35% to 40% and 25%, respectively. In Turkey, the estimated prevalence of cigarette smoking rate in the normal population is 26%. This study evaluated the rate of smoking in 63 cadaveric, and 158 living-related renal transplant recipients including (150 men, and 76 women of 38 +/- 12 years; range, 8 to 70) who were operated between 1986 and 2001. Demographic data were collected with a questionnaire delivered to patients during their routine outpatient visits. During this time period, 8 patients had died, 4 from hemophagocytic syndrome, 2 from cardiovascular disease, 1 from Kaposi sarcoma and 1 from a cerebrovascular accident. Twenty-three patients have lost their grafts. While at the time of transplantation 97 (42%) were smoking cigarettes, only 29 (12%) continued smoke after transplantation. Male gender significantly correlated with cigarette smoking (P =.000). Twelve smokers were single but 85 out of 97 were married, a statistically significant difference (P =.010). In contrast there was no significant relationship between pretransplant smoking and educational status (P =.354); graft loss and smoking (P =.129); or mortality and smoking (P =.224). There was a significant relationship between pretransplant and posttransplant smoking (P =.000). There was no relationship between pre- and post-transplant smoking and development of diabetes mellitus or hypertension. Interestingly the posttransplant serum albumin level was lower among smokers than nonsmokers (4.44 +/- 0.02 g/dL vs 4.30 +/- 0.02 g/dL; P =.019). There was a close relationship between transplantation duration and smoking.     

Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients?

BACKGROUND: Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that has been shown to be superior to azathioprine in preventing early acute rejection in the general renal transplant population. However, it is uncertain whether these benefits also apply to older renal transplant recipients, who are known to be more susceptible to infectious complications and have considerably lower rates of rejection and immunological graft loss. METHODS: A retrospective analysis was undertaken of all elderly (> or =55 years old) renal transplant recipients who underwent renal transplantation at the Princess Alexandra Hospital (1994-2000) and received either MMF (n=60) or azathioprine (n=55) in combination with prednisolone and cyclosporin. Data were analyzed on an intention-to-treat basis using a multivariate Cox proportional hazards model. RESULTS: The azathioprine- and MMF-treated groups were well matched at baseline with respect to demographic characteristics, end-stage renal failure causes and transplant characteristics. Compared with the MMF cohort, azathioprine-treated patients experienced a shorter time to first rejection [hazard ratio (HR) 4.47, 95% CI 1.53-13.1, P<0.01]. However, azathioprine-treated patients were also less likely to develop opportunistic infections (HR 0.11, 95% CI 0.03-0.41, P=0.001). No differences were observed between the two groups with respect to hospitalization rates, intensive care admissions, hematological complications, or posttransplant malignancies. Actuarial 2-year survival rates for the azathioprine- and MMF-treated patients were 100 and 87%, respectively (P<0.001). The principal cause of death in the MMF cohort was infection. Using a multivariate Cox regression analysis of patient survival, an adjusted hazard ratio of 0.01 (95% CI 0.001-0.08, P=0.001) was calculated in favor of azathioprine. Overall graft survival also tended to be better in patients receiving azathioprine (HR 0.27, 95% CI 0.06-1.33, P=0.11), CONCLUSIONS: In elderly renal transplant recipients, the combination of MMF, cyclosporin, and prednisolone appears to result in a worse outcome compared with the less potent combination of azathioprine, cyclosporin, and prednisolone. Future prospective studies need to specifically evaluate the risk/benefit ratios of newer, more potent immunosuppressive protocols, such as MMF-based regimens, in this important and sizeable patient subgroup.     

Patient survival after renal transplantation: II. The impact of smoking

Renal transplant recipients have significantly higher mortality than individuals without kidney disease and the excess mortality is mainly due to cardiovascular causes. In this study, we sought to determine the impact of smoking, a major cardiovascular risk factor, on patient and renal graft survival. The study population included all adult recipients of first cadaveric kidney transplants done in our institution from 1984 to 1991. By selection, all patients were alive and had a functioning graft for at least 1 yr after transplantation. Smoking history was gathered prior to transplantation. The follow-up period was 84.3 + 41 months and during this time 28%, of the patients died and 21%, lost their graft. By univariate and multivariate analysis, patient survival, censored at the time of graft loss, correlated with these pre-transplant variables: age (p < 0.0001); diabetes (p = 0.0002); history of cigarette smoking (p = 0.004); time on dialysis prior to the transplant (p = 0.0005); and cardiomegaly by chest X-ray (p = 0.0005). Post-transplant variables did not correlate with patient mortality. By Cox regression, patient survival time was significantly shorter in diabetics (p < 0.0001), smokers (p = 0.0005), and recipients older than 40 yr. However, there were no significant differences between the survival of smokers, non-diabetics, diabetics, and older recipients. Patient death was the most common cause of renal transplant failure in smokers, in patients older than 40 yr, and in diabetics, but these patient characteristics did not correlate with graft survival. The prevalence of different causes of death was not significantly different between smokers and non-smokers. In conclusion, a history of cigarette smoking correlates with decreased patient survival after transplantation, and the magnitude of the negative impact of smoking in renal transplant recipients is quantitatively similar to that of diabetes.     

Wait List Death and Survival Benefit of Kidney Transplantation Among Nonrenal Transplant Recipients

The disparity between the number of patients waiting for kidney transplantation and the limited supply of kidney allografts has renewed interest in the benefit from kidney transplantation experienced by different groups. This study evaluated kidney transplant survival benefit in prior nonrenal transplant recipients (kidney after liver, KALi; lung, KALu; heart, KAH) compared to primary isolated (KA1) or repeat isolated kidney (KA2) transplant. Multivariable Cox regression models were fit using UNOS data for patients wait listed and transplanted from 1995 to 2008. Compared to KA1, the risk of death on the wait list was lower for KA2 (p < 0.001;HR = 0.84;CI = 0.81–0.88), but substantially higher for KALu (p < 0.001; HR = 3.80;CI = 3.08–4.69), KAH (p < 0.001; HR = 1.92; CI = 1.66–2.22), and KALi (p < 0.001; HR = 2.69; CI = 2.46–2.95). Following kidney transplant, patient survival was greatest for KA1, similar among KA2, KALi, KAH, and inferior for KALu. Compared to the entire wait list, renal transplantation was associated with a survival benefit among all groups except KALu (p = 0.017; HR = 1.61; CI = 1.09–2.38), where posttransplant survival was inferior to the wait list population. Recipients of KA1 kidney transplantation have the greatest posttransplant survival and compared to the overall kidney wait list, the greatest survival benefit.     

Effect of kidney transplantation on outcomes among patients with hepatitis C

The long-term outcome of kidney transplantation in patients infected with hepatitis C virus (HCV) and end stage renal disease (ESRD) is not well described. We retrospectively identified 230 HCV-infected patients using enzyme immunoassay and nucleic acid testing obtained during the transplant evaluation. Of 207 patients who had a liver biopsy before transplant, 44 underwent 51 follow-up liver biopsies at approximately 5-year intervals either while on the waitlist for a kidney or after kidney transplantation. Advanced fibrosis was present in 10% of patients biopsied, identifying a population that may warrant consideration for combined liver-kidney transplantation. Kidney transplantation does not seem to accelerate liver injury; 77% of kidney recipients who underwent follow-up biopsies showed stable or improved liver histology. There was a higher risk for death during the first 6 months after transplant, but undergoing transplantation conferred a long-term survival advantage over remaining on the waitlist, which was evident by 6 months after transplant (HR, 0.32; 95% CI, 0.17 to 0.62). Furthermore, the risk for death resulting from infection was significantly higher during the first 6 months after transplant (HR, 26.6; 95% CI, 5.01 to 141.3), whereas there was an early (≤6 months) and sustained decrease in the risk for cardiovascular death (HR, 0.20; 95% CI, 0.08 to 0.47). In summary, these data suggest the importance of liver biopsy before transplant and show that kidney transplantation confers a long-term survival benefit among HCV-infected patients with ESRD compared with remaining on the waitlist. Nevertheless, the higher incidence of early infection-related deaths after transplant calls for further study to determine the optimal immunosuppressive protocol.