Impact of donor obesity and donation after cardiac death on outcomes after kidney transplantation

The effect of donor body mass index (BMI) and donor type on kidney transplant outcomes has not been well studied. Scientific Registry of Transplant Recipients data on recipients of deceased-donor kidneys between 1997 and 2010 were reviewed. Donors were categorized by DCD status (DCD, 6932; non-DCD, 90,158) and BMI groups at 5 kg/m(2) increments: 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, 40-44.9, and ≥ 45 kg/m(2) . The primary outcome, death-censored graft survival (DCGS), was adjusted for donor, recipient, and transplant characteristics. Among recipients of non-DCD kidneys, donor BMI was not associated with DCGS. Among DCD recipients, donor BMI was not associated with DCGS for donor BMI categories < 45 kg/m(2) ; however, donor BMI ≥ 45 kg/m(2) was independently associated with DCGS compared to BMI of 20-24.9 kg/m(2) (adjusted hazard ratio, 1.84; 95% CI, 1.23, 2.74). The adjusted odds of delayed graft function (DGF) was greater for each level of BMI above reference for both DCD and non-DCD groups. There was no association of donor BMI with one-yr acute rejection for either type of donor. Although BMI is associated with DGF, long-term graft survival is not affected except in the combination of DCD with extreme donor BMI ≥ 45.     

A longitudinal perspective on neurodevelopmental outcome after infant cardiac transplantation.

BACKGROUND: With improvement in medical outcomes, the current research has shifted toward understanding and enhancing the quality of life after pediatric heart transplantation. Previous research has indicated that infant heart transplant recipients are generally at risk for neurodevelopmental delays; however, no longitudinal studies exploring the patterns of development within this medical population have been performed. METHODS: Using the Bayley Scales of Infant Development-II, 39 children (2 to 38 months of age) who underwent heart transplantation in infancy (<1 year) at Loma Linda University Children's Hospital were assessed consecutively over time. RESULTS: Mean Mental Development Index (MDI) scores for all age groups were within normal limits, except for the age ranges of 18 to 23 and 24 to 35 months, which were mildly delayed. Average Psychomoter Development Index (PDI) scores for all age groups reflected mildly delayed performance, except for the 36- to 38-month age group, which was within normal limits. Repeated measures analyses of variance on a sub-set of participants with at least 4 consecutive assessments revealed within-subject effects on MDI scores (F = 5.7, p < 0.01), but not on PDI scores (F = 1.6, p = 0.22). Significant decreases in MDI scores at 18 and 28 to 36 months were noted. CONCLUSIONS: Motor development in this population was consistently mildly delayed. Age-dependent variability in cognitive skills was apparent. The delays appeared due to speech/language acquisition (18 months), and abstract reasoning/goal-directed behaviors (28 to 36 months). Possible etiologies for cognitive delays include test artifacts, auditory functioning and effects of immunosuppressive agents. Understanding risk factors in this patient population will allow for early and effective intervention.     

Influence of mast cells on outcome after heterotopic cardiac transplantation in rats

Correlative data suggest that mast cells adversely affect cardiac transplantation. This study uses a mast cell-deficient rat model to directly address the role of mast cells in cardiac allotransplantation. Standardized cardiac heterotopic transplantation with cyclosporine immunosuppression was performed in mast cell-deficient and mast cell-competent rats. Rejection, ischemia, fibrosis, fibrin deposition, numbers of T-cell receptor alpha/beta positive cells, expression of transforming growth factor-beta (TGF-beta), and of endothelin-1 (ET-1) and its receptors ETA and ETB were assessed. Differences in baseline cardiac gene expression were quantified by real-time PCR in a separate group of untransplanted animals. Baseline cardiac gene expression levels of all investigated growth factors, cytokines, ET-1, ETA, and ETB were similar in mast cell-deficient and mast cell-competent rats. Surprisingly, upon heterotopic transplantation, donor heart survival was significantly reduced in mast cell-deficient rats. Moreover, in mast cell-deficient donor hearts rejection was more severe, although nonsignificant, and extracellular matrix associated TGF-beta immunoreactivity was significantly lower than in mast cell-competent donor hearts. Fibrin immunoreactive area, on the other hand, was only increased in mast cell-deficient donor hearts, but not in mast cell-competent donor hearts. Histopathological changes in all donor hearts were accompanied by increased immunoreactivity for ET-1. In conclusion, this study shows that mast cells play a protective role after cardiac transplantation.     

Effect of prior cardiac surgery on survival after heart transplantation

We conducted a retrospective analysis of 182 adult orthotopic heart transplant patients who underwent operations at our institution between July 1982 and October 1987 to determine whether prior cardiac operation affects survival. Group I included the 72 patients (39.6%) who had undergone a previous cardiac operation or operations and group II, the 110 (60.4%) who had not. The mean age of the patients in group I was 52.1 +/- 8.1 years and in group II, 46.1 +/- 10.2 years (p less than 0.01). The incidence of ischemic heart disease was 86.1% in group I and 29.1% in group II (p less than 0.01). All patients received cyclosporine-based immunosuppression. More patients in group I than in group II required reoperation for bleeding after transplantation: 18 (25.0%) versus 9 (8.2%) (p less than 0.01). The actuarial 1-year and 3-year survival rates were 77.6% and 66.5%, respectively, for group I and 77.1% and 66.3%, respectively, for group II. Because both groups had similar survival rates, we believe that prior cardiac operation in heart transplant recipients does not compromise long-term survival.     

The role of obesity in kidney transplantation outcome

Background

The number of obese kidney transplant candidates has been growing. However, there are conflicting results regarding to the effect of obesity on kidney transplantation outcome. The aim of this study was to investigate the association between the body mass index (BMI) and graft survival by using continuous versus categoric BMI values as an independent risk factor in renal transplantation.

Methods

We retrospectively reviewed 376 kidney transplant recipients to evaluate graft and patient survivals between normal-weight, overweight, and obese patients at the time of transplantation, considering BMI as a categoric variable.

Results

Obese patients were more likely to be male and older than normal-weight recipients (P = .021; P = .002; respectively). Graft loss was significantly higher among obese compared with nonobese recipients. Obese patients displayed significantly lower survival compared with nonobese subjects at 1 year (76.9% vs 35.3%; P = .024) and 3 years (46.2% vs 11.8%; P = .035).

Conclusions

Obesity may represent an independent risk factor for graft loss and patient death. Careful patient selection with pretransplantation weight reduction is mandatory to reduce the rate of early posttransplantation complications and to improve long-term outcomes.     

Donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation

BACKGROUND: Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function. METHODS: We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support. RESULTS: Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome. CONCLUSIONS: Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.     

Late cardiac reoperation after cardiac transplantation

BACKGROUND: The intermediate and long-term results of cardiac transplantation continue to improve. Subsequent cardiac procedures may be required to extend patient survival and protect graft function. METHODS: The medical records of all adult and pediatric cardiac transplant recipients who underwent a subsequent cardiac procedure at our institution were reviewed. RESULTS: Three hundred sixty patients have undergone primary orthotopic transplantation in our institution. Seventeen patients (12 adults, 5 children) underwent a subsequent procedure requiring cardiopulmonary bypass including cardiac retransplantation (10), coronary artery bypass grafting (3), ascending aortic replacement (2), tricuspid valve repair (1), and myotomy and myomectomy (1 patient). Mean interval from time of transplantation to second procedure was 8.3 years. There was one perioperative death. Two patients, both retransplants, died late postoperatively at 22 and 84 months, respectively. Overall mean follow-up in the late survivors is 26.6 months. All survivors are currently asymptomatic and doing well. CONCLUSIONS: A variety of subsequent cardiac procedures, in addition to retransplantation, can be performed safely in carefully selected cardiac transplant recipients. The intermediate term results are gratifying in terms of survival and freedom from symptoms.     

Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

Effect of calcitriol on bone loss after cardiac or lung transplantation.

Rapid bone loss after cardiac and lung transplantation results in an increased risk of osteoporotic fracture. This study examined the efficacy of treatment with calcitriol (1,25-dihydroxyvitamin D3) in preventing bone loss in patients undergoing cardiac or lung transplantation. In this 2-year double-blind, stratified study, 65 patients undergoing cardiac or single lung transplantation were randomly allocated to receive either placebo or calcitriol (0.5-0.75 microg/day), the latter for either 12 months or 24 months. All patients received 600 mg calcium/day. Bone mineral density (BMD) was measured every 6 months for 2 years by dual-energy X-ray absorptiometry. There was no significant difference between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporine over the 2 years. Bone loss at the proximal femur was significantly reduced or prevented at all three sites by treatment with calcitriol for 2 years compared with treatment with calcium alone. Treatment with calcitriol for 12 months followed by calcium for 12 months resulted in similar proximal femoral bone loss to that seen in those patients treated with calcium for 24 months, suggesting calcitriol prophylaxis needs to be continued beyond 12 months. At the lumbar spine, there were no significant differences in BMD between groups. Over a period of 2 years, 22 new vertebral fractures/deformities occurred in 4 patients treated with calcium alone compared with one new vertebral fracture in 1 patient treated with calcitriol. Because the sample size was too low to provide reliable interpretation of vertebral fracture rates, this difference is likely a chance result. Mild hypercalcemia was common with calcitriol therapy, as was mild hypercalciuria (59% of patients vs. 10% controls), but there were no significant differences between groups in serum creatinine after 2 years. These data suggest calcitriol has a role in reducing proximal femur bone loss after cardiac or lung transplantation but treatment needs to be continued beyond 1 year.     

心脏移植术后的骨质疏松症

目的 研究心脏移植后患者的骨质疏松症的发病情况。方法 采用双能Ｘ线吸收扫描仪（ＤＸＡ）测定５３例心脏移植患者和２２例准备接受心脏移植患者的腰椎和股肌骨颈的骨矿密度（ＢＭＩ）。     

Effects of pre-transplant dialysis modality on early outcome of kidney transplantation from donation after cardiac death

Objective To compare the influence of hemodialysis (HD) and peritoneal dialysis (PD) on early outcome of patients underwent kidney transplantation from donation after cardiac death (DCD). Methods Patients admitted in the First People's Hospital of Foshan with DCD kidney transplant from January 1st, 2011 to June 30th, 2016 were analyzed retrospectively. Recipients were grouped into HD group (n=61) and PD group (n=28) according to their pre-transplant dialysis modality. Their short-term outcomes after DCD kidney transplant were compared, including recovery of renal function, short-term complications and laboratory data. Results Patients had longer dialysis duration and lower hemoglobin, serum albumin and phosphorus in PD group than those in HD group (all P＜0.05), but no significant difference shown in age, gender, body mass index, primary disease, blood pressure, and hepatitis B infection (all P＞0.05). HD patients with 6.00(4.00, 11.00) d recovery time of renal function, 18.00(17.00, 21.50) d hospital time, had 24.59% the delayed graft function (DGF), 3.28% acute rejection and 16.39% infection during hospitalization. While for PD patients the recovery time of renal function was 4.00(3.75, 7.00) d; hospital time was 19.00(15.00, 21.75) d; the incidence rate of DGF was 14.29%; acute rejection was 3.57%; and infection during hospitalization reached 17.86%. Above indexes were not significantly different between HD and PD groups (all P＞0.05). Repeated measure ments showed that, compared with those before transplant surgery, after 1 month, 3 months and 6 months HD and PD groups had decreased creatinine and phosphorus, and increased hemoglobinserum albumin and calcium; Serum albumin and calcium were different between the two groups (P＜0.001, P=0.040), whereas creatinine, hemoglobin and phosphorus did not show difference (all P＜0.05). After transplantation the trends of creatinine, hemoglobin, calcium and phosphorus were not different between the two groups (P values were 0.295, 0.310, 0.501 and 0.063, respectively). Conclusions No significant difference of the recovery regarding renal function, anemia, nutrition status and mineral metabolites was found between pre-transplant HD and PD modality in patients who underwent DCD kidney transplantations.     

Clinical and financial impact of obesity on the outcome of liver transplantation

The purpose of this study was to determine whether body mass index (BMI) influences the clinical outcomes and overall cost of transplantation in adult liver transplantation (OLT) using records of 700 adult OLT recipients. Patients were divided into BMI range groups over the range of 15 to 42 (mean = 26.7), namely: <25, n = 288 (41%); 25 to 30, n = 245 (35%); > or =30, n = 167 (24%). Only a small subset of this last group was morbidly obese (BMI > or = 35, n = 37, 5% of total). We did not detect an effect of BMI on patient or graft survival, the incidence of acute graft rejection, or major surgical complications. BMI was not related to length of hospital stay. There were no statistical differences between the three groups with respect to the ratio of overall hospital cost in a general linear model, corrected for age, gender, calculated Model for End-Stage Liver Disease score, retransplant status, or return to the operating room. In conclusion, obesity did not influence either the costs or the clinical outcomes following OLT. Further analysis of the morbidly obese population with respect to cost and outcome is warranted.     

Effect of overweight on kidney transplantation outcome

INTRODUCTION: Obesity is a prevalent problem in renal transplant recipients that is followed by reduced graft and patient survivals. Because the prevalence of overweight (OW) is increasing in the renal transplant population, we studied the influence of OW on graft and recipient evolution. PATIENTS AND METHODS: We analyzed a series of 337 patients with renal allografts having a mean follow-up of 53.4 +/- 30.6 months. We excluded 39 patients obese at transplantation. We compared the evolution of 134 OW patients (45.5%), and 160 patients (54.4%) with a body mass index <25 (NW group). RESULTS: OW patients were older (P = .000) with a higher prevalence of hypertension (P = .028), left ventricular hypertrophy (P = .014), and dyslipidemia (P = .001). They had received kidneys from older donors (P = .019). OW patients showed a higher incidence of acute tubular necrosis (ATN) (P = .006), without a higher incidence of acute rejection episodes (P = .756). Postransplant diabetes mellitus was more frequent (P = .000), and systolic blood pressure (P < .05), total cholesterol (P < .05), and tryglicerides were higher (P < .05) in the OW group. Serum creatinine at 6 months (P = .007) and proteinuria >0.5 g/24 hours, (P = .023) were higher among the OW group. Graft survival was not different between groups, but patient survival was lower in the OW group (P = .002). A logistic regression analysis showed that the recipient age (RR: 5.243) and the presence of OW (RR: 1.100) were independent prognostic factors for patient death. CONCLUSIONS: OW was a common situation among renal transplant candidates. It was associated with worse cardiovascular and metabolic profiles. OW patients showed worse allograft function and lower patient survival. A major effort must be exerted to avoid excessive weight gain, particularly among those OW at transplantation.     

Influence of mild obesity on outcome of simultaneous pancreas and kidney transplantation

The influence of body mass index (BMI) on outcome of simultaneous pancreas-kidney transplantation (SPK) has not been well described. We retrospectively reviewed 88 consecutive primary SPKs performed at our institution between March 15, 1995 and August 28, 2001. All patients received antibody induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Systemicenteric implantation was performed in all patients. Primary end points were patient, pancreas, and kidney survival. Secondary end points were rates of anastomotic leakage, pancreas thrombosis, major infection, rejection, repeat laparotomy, and length of hospital stay. Values are shown as mean ± standard deviation, range, or percentage. Fifty-two patients (59.1%) were nonobese with a BMI ≦24.9 (mean 21.7 ± 2.2, range 15.4 to 24.9). Thirty-six patients were mild to moderately obese with a BMI ≧25 (mean 27.7 ± 2.2, range 25 to 35.1). Distribution of recipient age, sex, and ethnicity was similar between groups. Kidney and pancreas preservation times were similar between nonobese and obese patients. One-, three-, and five-year actuarial patient (nonobese: 95%, 95%, 95% vs. obese: 95%, 95%, 89%), kidney graft (nonobese: 91%, 91%, 87% vs. obese: 97%, 91%, 85%), and pancreas graft (nonobese: 78%, 78%, 73% vs. obese: 70%, 62%, 62%) survival were comparable between nonobese and obese (P = NS). The mean rates of pancreas thrombosis, major infection, pancreas rejection, kidney rejection, relaparotomy, and length of hospital stay were similar in the two groups. The overall duodenojejunal anastomotic leakage rate was 8%. Obese patients had a 17% incidence of leakage (6 of 36) compared to a 2% incidence of leakage in nonobese patients (P = 0.012). Six of seven leaks occurred in obese patients. Mean BMI in the seven patients with a leak (27 ± 1.9) was significantly higher than in patients who did not develop a leak (24 ± 3.7; P = 0.05). Although obesity had no effect on patient or graft survival, it was associated with a significantly higher leakage rate. There should therefore be a higher degree of suspicion for the presence of duodenojejunal anastomotic leaks in obese SPK recipients. Presented at the American Hepato-Pancreato-Biliary Association Congress, Miami, Florida, February 28, 2003.