May-Thurner syndrome in renal transplantation.
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Biomedical subjects
Publications and source records attributed to J S Najarian.
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OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. SUMMARY BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. METHODS: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories. CONCLUSIONS: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.
BACKGROUND: There is a debate about the relative contribution of immunologic (rejection) and nonimmunologic (limited nephron mass) factors in long-term graft survival. METHODS: Using multivariate analysis, we studied the association of the following variables with outcome: delayed graft function (DGF), acute rejection, recipient race (black vs. nonblack), donor age (<50 vs. > or =50), donor race, and donor and recipient gender. Because of the association between DGF and rejection, recipients were grouped as follows: DGF, rejection; DGF, no rejection; no DGF, rejection; no DGF, no rejection. Data were analyzed on 1199 first kidney transplants in adults (752 living donor, 447 cadaver donor) done between January 1, 1985 and December 31, 1996. Two analyses were done: first, all transplants; second, only those with > or =1 year survival. For both, there was no difference in risk factors if death with function was or was not censored. RESULTS: For all cadaver transplant recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50. For living donor recipients, only acute rejection was a risk factor. When only 1-year graft survivors were considered, risk factors were the same: for cadaver recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50; for living donor recipients the risk factor was rejection. CONCLUSION: We found immunologic factors (rejection with or without DGF) to be significant in both living donor and cadaver donor transplants. Nonim. munologic factors (donor age, recipient race) were significant only in cadaver donor transplants.
BACKGROUND: Transplant candidates frequently ask whether they should, based on information available at the time, accept a cadaver kidney or wait for a potentially better one. METHODS: We analyzed 937 first and second cadaver transplants done between January 1, 1984 and December 31, 1997 to determine if information available at the time an offer is made could be used to predict long-term graft survival. RESULTS: By Cox regression, risk factors for worse long-term graft survival were older donor age, cardiovascular or cerebrovascular cause of donor death, and delayed graft function (DGF). HLA-ABDR mismatch was marginally significant. Whether DGF will occur is not known at the time of an offer, but risk factors can be determined; we found these to be older donor age and > 10% panel-reactive antibodies (PRA) at transplantation (by Cox regression). Using these variables (PRA, ABDR mismatch, donor age, and donor cause of death) known at the time of an offer, we calculated the relative risk of worse long-term graft survival for each subgroup (Table 3 in manuscript). In general, older age and donor death from cardiovascular or cerebrovascular disease were associated with worse outcome. Kidneys from donors of < 50 yr had the best outcome, irrespective of match. CONCLUSION: The data provided can be used to help guide patients as to whether they are better off accepting an offered kidney or waiting for a potentially better one. If an offer is declined, the next kidney may have a potentially worse outcome.
OBJECTIVE: To determine whether a recent decrease in the rate of acute rejection after kidney transplantation was associated with a decrease in the rate of chronic rejection. SUMMARY BACKGROUND DATA: Single-institution and multicenter retrospective analyses have identified acute rejection episodes as the major risk factor for chronic rejection after kidney transplantation. However, to date, no study has shown that a decrease in the rate of acute rejection leads to a decrease in the rate of chronic rejection. METHODS: The authors studied patient populations who underwent transplants at a single center during two eras (1984-1987 and 1991-1994) to determine the rate of biopsy-proven acute rejection, the rate of biopsy-proven chronic rejection, and the graft half-life. RESULTS: Recipients who underwent transplantation in era 2 had a decreased rate of biopsy-proven acute rejection compared with era 1 (p < 0.05). This decrease was associated with a decreased rate of biopsy-proven chronic rejection for both cadaver (p = 0.0001) and living donor (p = 0.08) recipients. A trend was observed toward increased graft half-life in era 2 (p = NS). CONCLUSIONS: Development of immunosuppressive protocols that decrease the rate of acute rejection should lower the rate of chronic rejection and improve long-term graft survival.
BACKGROUND: We reviewed the incidence of and risk factors for venous thromboembolic complications in our population of kidney (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients. METHODS: Information was collected retrospectively from a database on 1833 KTx and 276 SPK recipients who underwent transplant surgery between January 1985 and August 1995. RESULTS: The incidence of deep venous thrombosis (DVT) was 6.2% (n= 132), with significantly higher rates after SPK (18.1%) vs. KTx (4.5%) (P < 0.001). The number of DVT episodes was highest in the first month; 17.5% occurred during this time. For KTx recipients, early thrombotic events were more common on the side of the graft (P=0.03); however, after 1 month, no correlation existed between the side of the graft and the side of DVT. For SPK recipients, DVT tended to be more common on the side of the pancreas (57%) vs. the kidney (43%) (P=0.10). By multivariate analysis, risk factors for DVT were: age > 40 years (odds ratio [OR]=2.2, P < 0.001), diabetes mellitus (DM) (OR=2.0, P=0.002), previous DVT (OR=4.4, P=0.001), and SPK transplant (OR=2.8, P < 0.001). Pulmonary embolus (PE) was identified in 44 recipients (incidence, 2.1%) and was fatal in 13 (30%). The incidence was significantly higher in SPK (4.71%) vs. KTx recipients (1.69%) (P < 0.01). The risk of death from PE was 0.5% in KTx recipients and 1.37% in SPK recipients (P=0.08). Risk factors for PE included DM (OR=2.6, P=0.005) and recent DVT (OR=8.9, P=0.0001). CONCLUSIONS: Based on risk and extrapolating from the general surgical literature, our recommendations for prophylaxis against DVT are use of graduated compression stockings for all recipients and, in addition, low-dose heparin for moderate and high-risk recipients (previous DVT, SPK, age > 40 years, DM).
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OBJECTIVE: The optimal age for transplantation in children with end-stage renal disease remains controversial. Supported by national data, many centers recommend dialysis until the child reaches a certain minimum age. The authors' policy, however, has been to encourage living donor (LD) transplants for young children, with no minimum age restriction. METHODS: Between January 1, 1984, and December 31, 1996, the authors performed 248 kidney transplants in children younger than age 13 years, using cyclosporine as the primary immunosuppressive agent. Recipients were analyzed in three age groups: group 1, younger than age 1 year (n = 26); group 2, age 1 through 4 (n = 92); and group 3, age 5 through 13 (n = 130). Almost all recipients in group 1 underwent a primary LD transplant. Therefore, to compare results more meaningfully among the three age groups, only primary LD transplants were analyzed (group 1, n = 25; group 2, n = 59; group 3, n = 58). RESULTS: In primary LD transplants, no significant difference was noted among the age groups in 1-and 5-year patient or graft survival rates. To date, all 25 recipients from group 1 are alive and well; 19 still have a functional original graft. Causes of graft loss in the remaining six recipients were chronic rejection (n = 3), vascular thrombosis (n = 2), and recurrent disease (n = 1). The incidence of acute rejection in group 1 recipients was lower than in the two older groups. However, the incidence of delayed graft function was slightly higher in the youngest group than in the two older groups. For recipients in group 1, growth (as measured by weight) improved significantly posttransplant: the mean standard deviation score rose from -2.8 pretransplant to -0.2 by age 5 and to +1.8 by age 10. The improvement in height was not as dramatic: the mean standard deviation score rose from -3.2 pretransplant to -1.6 by age 5 and to -1.4 by age 10. CONCLUSIONS: Kidney transplantation in young children, including those younger than 1 year old, can achieve results comparable to those in older children. As long as an adult LD is available, the timing of the transplant should be based on renal function rather than age.
BACKGROUND: The purpose of this study was to review arterial thromboembolic complications presenting with an acutely ischemic lower extremity after a kidney (KTx) or simultaneous kidney-pancreas transplantation (SPK) and to describe an approach to their management. METHODS: We retrospectively reviewed all such transplantations (a total of 2109) performed between January 1985 and August 1995. We identified 16 recipients (incidence, 0.76%) in whom an acutely ischemic leg developed during the immediate postoperative period (within the first 48 hours). RESULTS: Of the 16 recipients, eight underwent a KTx (incidence, 0.45%) and eight underwent an SPK transplantation (incidence, 2.90%). Median age was 38 years (range, 15 months to 61 years). Thirteen had insulin-dependent diabetes mellitus (IDDM), a significantly higher incidence than in the control group (i.e., transplant recipients without this complication) (p < 0.01). Peripheral vascular disease (PVD) was documented before operation in eight (50%) of the recipients (vs 8.9% in the control group) (p < 0.01). Ten were uremic (on chronic dialysis) before transplantation; six were nonuremic (not on dialysis). Intraoperatively, 14 had moderate to severe atherosclerotic disease affecting the iliac vessels, seven of whom required some manipulation of the artery (either endarterectomy or tacking of the intima) to make it suitable for anastomosis. Heparin was administered systemically during cross clamping to only four. Most of the 16 recipients showed symptoms or signs of arterial occlusion within the first few hours after operation. The most common symptom was pain; the most common physical finding was loss of femoral and distal pulses. Thirteen recipients had moderate to severe ischemia, as judged by physical examination; 15 returned to the operating room for surgical exploration. Eight underwent thrombectomy through an inguinal incision, with successful restoration of flow. Seven underwent exploration through the initial incision because of concern regarding the viability of the transplanted organ; five of them required transplant nephrectomy because of simultaneous thrombosis of the renal artery. No patient needed a bypass procedure to restore flow. Long-term morbidity as a result of the arterial occlusion was related to the severity and length of ischemia. CONCLUSIONS: On the basis of these results, we suggest the following recommendations: (1) all patients should undergo a thorough peripheral vascular examination before and after transplantation; (2) patients at higher risk for arterial thromboembolic complications (e.g., those with significantly diseased vessel at intraoperative examination, nonuremic patients) should receive intraoperative systemic heparin before cross clamping of the artery; and (3) patients with signs or symptoms suggesting arterial occlusion after operation should undergo prompt surgical exploration.
We are using a validated questionnaire (SF-36) to annually assess health-related quality of life (QOL) in kidney and pancreas-kidney transplant recipients. The SF-36 consists of eight scales to assess physical functioning, general health, and mental functioning. Norms and 95% confidence intervals (C.I.) have been developed for the US population. At present, 1138 recipients with functioning grafts (520 Type I diabetic; 618 nondiabetic) 1-10 yr post-transplant have completed the questionnaire. Of the recipients, 446 completed the questionnaire once; 632 twice; and 53 three times (305 after 1 yr; 266 after 2 yr; 256 after 3 yr; 206 after 4 yr; 192 after 5 yr; 150 after 6 yr; 130 after 7 yr; 138 after 8 yr; 125 after 9 yr; 92 after 10 yr). For both diabetic and nondiabetic recipients, there was little change in average scores for each scale between years (p = NS). In relation to the US population, average scores for nondiabetics were below the 50th percentile on all 8 scales; for diabetics < 25th percentile on the physical functioning and vitality scales, < 50th percentile on all others. For both diabetic and nondiabetic recipients, average scores were higher than reported norms for patients with CHF, COPD, or depression but were similar to those with Htn or recent MI. Individual scores were then compared with age-matched means (+/- 2 SEMs) (95% C.I.) for the US population. At each year post-transplant, up to 40% of nondiabetic and up to 65% of diabetic recipients had scores below the 95% C.I. on individual scales (particularly the physical functioning and general health scales)--e.g. over 30% nondiabetic and up to 60% diabetic recipients had scores on the physical functioning scales below the 95% C.I. More diabetic recipients (vs. nondiabetics) reported poor QOL on the physical functioning, general health and social functioning scales. There was little difference in the mental health scales. For those with Type I diabetes, a similar percentage of kidney and K/P recipients reported QOL below the 95% C.I. for the age-matched population, except on the GH scale (better QOL for K/P recipients). We conclude that successful transplant recipients report health-related QOL below that of the age-matched general population but similar to those with other chronic diseases. Diabetic and nondiabetic recipients have similar scores on the mental health scales; nondiabetic recipients score better on the general health and physical functioning scales.
BACKGROUND: Simultaneous pancreas-kidney transplantation has become a widely accepted treatment option for selected uremic patients with insulin-dependent diabetes mellitus (IDDM). Patient survival rates at 1 year exceed 90%, and rates of pancreas graft survival, 70%. However, solitary pancreas transplantation for nonuremic patients with IDDM has been controversial because of the less favorable outcome and the need for long-term immunosuppression with its associated morbidity and mortality. METHODS: We studied the outcome of 225 solitary pancreas transplants during three immunosuppressive eras: the precyclosporine (CsA) era (n=83), the CsA era (n=118), and the tacrolimus era (n=24). Only patients with labile IDDM (e.g., hypoglycemic unawareness, insulin reactions, > or = 2 failed attempts at intensified insulin therapy for metabolic control) underwent solitary pancreas transplantation. Using univariate and multivariate analyses, we looked at patient and graft survival, the risk of surgical complications, and native kidney function during these three eras. RESULTS: Pancreas graft survival improved significantly over time: 34% at 1 year after transplantation in the pre-CsA era, 52% in the CsA era, and 80% in the tacrolimus era (P=0.002). Pancreas graft loss due to rejection decreased from 50% at 1 year in the pre-CsA era, to 34% in the CsA era, to 9% in the tacrolimus era (P=0.008). The rate of technical failures (i.e., the risk of surgical complications) decreased from 30% in the pre-CsA era, to 14% in the CsA era, to 0% in the tacrolimus era (P=0.001). Patient survival rates at 1 year have ranged between 88% and 95% in the three eras (P=NS). Matching for at least one antigen on each HLA locus and avoiding HLA-B mismatches significantly decreased the incidence of rejection. The incidence of native kidney failure due to drug-induced toxicity decreased significantly over time, in part because only recipients with pretransplant creatinine clearance > or = 80 ml/min received transplants. CONCLUSIONS: Solitary pancreas transplantation has become a viable alternative for nonuremic patients with labile IDDM. The risks of surgical complications and drug-induced nephrotoxicity have significantly decreased over time. Using tacrolimus as the mainstay immunosuppressant, patient and graft survival rates now no longer trail those of simultaneous pancreas-kidney transplantation.
BACKGROUND: Short- and long-term patient and graft survival rates are better for living donor (vs. cadaver) kidney transplant recipients. However, donor nephrectomy is associated with at least some morbidity and mortality. We have previously estimated the mortality of living donor nephrectomy to be 0.03%. In our present study, to determine associated perioperative morbidity, we reviewed donor nephrectomies performed at our institution from January 1, 1985, to December 31, 1995. METHODS: The records of 871 donors were complete and available for review. Of these donors, 380 (44%) were male and 491 (56%) were female. The mean age at the time of donation was 38 years (range: 17-74 years), and mean postoperative stay was 4.9 days (range: 2-14 days). RESULTS: We noted two (0.2%) major complications: femoral nerve compression with resulting weakness, and a retained sponge that required reexploration. We noted 86 minor complications in 69 (8%) donors: 22 (2.4%) suspected wound infections (only 1 wound was opened), 13 (1.5%) pneumothoraces (6 required intervention, 7 resolved spontaneously), 11 (1.3%) unexplained fevers, 8 (0.9%) instances of operative blood loss > or = 750 ml (not associated with other complications), 8 (0.9%) pneumonias (all of which resolved quickly with antibiotics alone), 5 (0.6%) wound hematomas or seromas (none were opened), 4 (0.5%) phlebitic intravenous sites, 3 (0.3%) urinary tract infections, 3 (0.3%) readmissions (2 for pain control and 1 for mild confusion that resolved with discontinuation of narcotics), 3 (0.3%) cases of atelectasis, 2 (0.2%) corneal abrasions, 1 (0.1%) subacute epididymitis, 1 (0.1%) Clostridium difficile colitis, 1 (0.1%) urethral trauma from catheter placement, and 1 (0.1%) enterotomy. At our institution, no donor died or required ventilation or intensive care. We noted no myocardial infarctions, deep wound infections, or reexplorations for bleeding. Analysis, by logistic regression, identified these significant risk factors for perioperative complications: male gender (vs. female, P<0.001), pleural entry (vs. no pleural entry, P<0.004), and weight > or = 100 kg (vs. < 100 kg, P<0.02). Similar analysis identified these significant risk factors for postoperative stay > 5 days: operative duration > or = 4 hr (vs. < 4 hr, P<0.001) and age > or = 50 years (vs. < 50 years, P<0.001). CONCLUSIONS: Living donor nephrectomy can be done with little major morbidity. The risks of nephrectomy must be balanced against the better outcome for recipients of living donor transplants.
Chronic rejection (CR) is the most common cause of graft loss beyond the 1st posttransplant year. The aim of this analysis was to identify the risk factors for the development of CR in pediatric renal transplant recipients. Between June 1984 and March 1994, 217 renal transplants were performed in children at our center. Immunosuppression included prednisone, azathioprine, cyclosporine (CsA), and prophylactic antibody. Using multivariate analysis, we studied the impact of the following variables on the development of biopsy-proven CR: age at transplant (< or = 5 years, > 5 years), gender, race, transplant number (primary, retransplant), donor source (cadaver, living donor), donor age (< 20 years, 20-49 years, > 49 years), number of ABDR mismatches (0, 1-2, 3-4, 5-6), number of DR mismatches (0, 1, 2), percentage peak panel reactive antibody (PRA) (< or = 50%, > 50%), percentage PRA at transplantation (< or = 50%, > 50%), dialysis pretransplant, preservation time > 24 h, acute tubular necrosis requiring dialysis, initial CsA dosage (< or = 5 mg/kg per day, > 5 mg/kg per day), CsA dosage at 1 year posttransplant (< or = 5 mg/kg per day, > 5 mg/kg per day), acute rejection (AR), number of AR episodes (ARE) (1, > 1), timing of AR (< or = 6 months, > 6 months), reversibility of AR (complete, partial), and infection [cytomegalovirus (CMV), non-CMV viral, bacterial]. Risk factors for the development of CR in pediatric renal transplant recipients were: AR (P < 0.0001, odds ratio 19.4), multiple ARE (> 1 vs. 1) (P < 0.0001, odds ratio 30.1), and high percentage peak PRA (> 50%) (P < 0.03, odds ratio 3.6).
Colon perforation (CP) is an uncommon but dramatic complication after renal transplantation. Of 1530 consecutive kidney transplants performed at our center, 8 recipients had an CP (incidence of 0.5%), either early (n = 5, 2-14 days) or late (n = 3, 8-48 months) post transplant. Clinical symptoms were generally vague. Biological findings were inconstant. Risk factors for CP included a cadaver graft (versus a living donor), high body weight, history of diverticulitis, and Kayexalate use. Crucial to outcome were: 1) immediate diagnosis and 2) aggressive surgical care consisting of resectional therapy, broad-spectrum antibiotics, and reduced immunosuppression. Applying these principles, mortality in our patients (25%) was lower than in previously reported series (33-64%). All grafts were functioning at the time of diagnosis; graft function was preserved in recipients who recovered from CP. Patients with a documented history of diverticulitis should undergo prophylactic colonic resection. Constipation and colonic dilatation should be treated aggressively in the early post-operative period.
A major variable in the cost of kidney transplants is the length of initial hospitalization. Using multivariate analysis, we studied risk factors for hospital stay > 10 d post-transplant. Between 1 January 1985 and 31 August 1995 a total of 1588 patients underwent first or second kidney transplants at the University of Minnesota. Antibody was used for 1 wk in cadaver donor recipients and for 2 wk in pediatric recipients (resulting in a long stay for all pediatric recipients). Adult living related donor recipients were immunosuppressed with triple therapy. Donor risk factors studied were age (< 15, 15-50, > 50 yr) and,- for cadaver recipients, preservation time (< 12, 12-18, 18-24, 24-30, > 30 h) and cause of death (trauma, cerebrovascular accident, or cardiac). Recipient risk factors studied were age (< 18, 18-55, > 55 yr); sex; transplant number; antigen mismatch; peak PRA; PRA at transplant (< 11, 11-50, > 50); diabetic status; pretransplant dialysis (vs. pre-emptive transplant); pretransplant cardiac, peripheral vascular, or respiratory disease; and delayed graft function (DGF) (dialysis in the first week vs. no dialysis). Risk factors were analyzed separately for living donor and cadaver donor recipients. For cadaver donor recipients, DGF was the major risk factor (p < 0.0001); others were age 55 yr (p = 0.03) and diabetes (p = 0.02). For living donor recipients, DGF was also a risk factor (p = 0.003); others were diabetes (p = 0.01), retransplant (p = 0.006), PRA at transplant > 50 (p < 0.0001), age > 55 yr (p = 0.02), pretransplant respiratory disease (p = 0.005), and pretransplant dialysis (p = 0.005). Because DGF was the major risk factor for a prolonged stay, we then studied risk factors for DGF using multivariate analysis. For cadaver donor recipients, risk factors were recipient weight > 90 kg (p = 0.004), preservation time 24 h (p = 0.03), PRA at transplant > 50 (p = 0.03), and donor age < 15 or > 50 yr (p = 0.002). For living donor recipients, risk factors were recipient age < 18 yr (p = 0.01), donor age > 50 yr (p = 0.03), female sex (p = 0.05), pretransplant respiratory disease (p = 0.1), pretransplant peripheral vascular disease (p = 0.05), and recipient weight > 90 kg (p = 0.1). From our data, a profile emerged of recipients likely to have a longer hospital stay. Important variables, either simultaneous with or related to DGF, include donor and recipient age, diabetes, pretransplant recipient weight, PRA at transplant, preservation time, and pretransplant respiratory or peripheral vascular disease.