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D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 37 records · Page 2Linked to original sources

Pre-emptive transplants for patients with renal failure: an argument against waiting until dialysis.

BACKGROUND: Pre-emptive kidney transplants have not been favored in some centers because of concern about possible increased noncompliance and allegedly inferior long-term results. We analyzed our experience with pre-emptive kidney transplants to determine whether such concerns are justified. PATIENTS AND METHODS: Between January 1, 1984, and June 30, 1998, we performed 1849 adult primary kidney transplants: 385 pre-emptive (recipients not undergoing dialysis, ND) and 1464 non-pre-emptive (recipients undergoing dialysis, D). Results were subdivided by donor source: cadaver (CAD) and living donor (LD). ND recipients tended to be younger, but otherwise, the two groups were similar. Posttransplantation quality of life in recipients was evaluated using the nationally standardized Short Form Health Survey (SF-36). The posttransplantation employment status of the recipients was also evaluated. RESULTS: The patient survival rate 5 years posttransplantation was significantly better for ND (vs. D) recipients for both CAD (92.6% vs. 76.6%, P=0.001) and LD (93.3% vs. 89.5%, P=0.02) transplants. The 5-year patient survival rate was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation for both CAD (P=0.0005) and LD (P=0.0001) transplants. The graft survival rate 5 years posttransplantation was similar between ND and D recipients for CAD transplants, but significantly better for ND (vs. D) recipients of LD transplants (92.3% vs. 84.8%, P=0.006). For CAD transplants, the 5-year graft survival rate was not different when ND recipients were compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation; for LD transplants it was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation (P=0.04). The incidence of acute and chronic rejection was no different between ND and D recipients for either CAD or LD transplants, and it was also not affected by the pretransplantation time undergoing dialysis. Graft loss secondary to the recipient's discontinuation of immunosuppressive therapy (a crude estimate of compliance) was similar between ND and D recipients. Five years posttransplantation, the SF-36 scores regarding the recipient's quality of life and the employment status were similar for ND compared with D recipients, regardless of donor source. CONCLUSIONS: ND recipients do not seem to have higher rates of noncompliance than D recipients. Results for ND recipients seem to be superior than for D recipients, supporting the contention that renal failure patients should, if possible, undergo transplantation before dialysis.

Actuarial Analysis↗

Increased incidence of cardiac complications in kidney transplant recipients with cytomegalovirus disease.

BACKGROUND: The transplant literature has not shown cytomegalovirus (CMV) disease to be a significant risk factor for posttransplant cardiac complications. A large number of nontransplant studies have, however, reported an association between coronary heart disease (CHD) and CMV disease. Pathology studies have demonstrated a high incidence of CMV in atheromatous plaques from the coronary circulation. METHODS: We performed multivariate analysis to determine if posttransplant CMV disease was a significant risk factor for cardiac complications in kidney transplant recipients. We also performed univariate analysis to determine which cardiac complications were more common in the recipients with CMV disease. RESULTS: Between January 1, 1984 and June 30, 1997, 1859 adults underwent kidney transplants at our institution. Of these, 377 developed one of the following cardiac complications posttransplant: myocardial infarction, angina, arrhythmia, congestive heart failure, and angiographic vessel occlusion. By multivariate analysis, significant risk factors for one of the above cardiac complications were recipient age >50 years [odds ratio (OR)=2.5, P=0.0001], diabetes (OR=1.99, P=0.0001), a history of cardiac disease pretransplant (OR= 1.34, P=0.04), and CMV disease (OR=1.5, P=0.01). Univariate analysis demonstrated that recipients with CMV disease had a higher overall incidence of cardiac complications. Arrhythmias, congestive heart failure, and vessel occlusion were more common in those with CMV disease. The incidence of myocardial infarction, angina, and cardiac arrest did not differ between the two groups (recipients with versus without CMV disease). CONCLUSIONS: CMV disease is associated with an increased risk of cardiac complications in kidney transplant recipients. In our series, angiographic vessel occlusion was more common in recipients with CMV disease. This interesting finding may support the theory that CMV plays some role in the pathogenesis of CHD.

Adult↗

Randomized, prospective trial of mycophenolate mofetil versus azathioprine for prevention of acute renal allograft rejection after simultaneous kidney-pancreas transplantation.

BACKGROUND: In simultaneous kidney-pancreas (SPK) transplantation, manifestations of renal allograft rejection typically become evident before those of pancreatic rejection. This study compared mycophenolate mofetil (MMF) and azathioprine (AZA) in prevention of renal rejection after primary SPK transplantation. METHODS: In an open-label, randomized, multicenter study, patients received MMF 1.5 g twice daily (n=74) or AZA 1-3 mg/kg daily (n=76) for 1 year after transplantation. The incidence of rejection was assessed at 6 months. Adverse events were tracked through 1 year. Survival data are reported through 2 years. RESULTS: At 6 months, efficacy results for MMF vs. AZA patients, respectively, were the following: rejection (27% vs. 39%); rejection or death (34% vs. 42%); rejection, graft loss, death, or premature withdrawal (i.e., treatment failure; 41% vs. 55%). Six-month efficacy trends favored MMF, and time to rejection or treatment failure was significantly longer when compared with AZA (P=0.049). One-year efficacy results for MMF vs. AZA patients, respectively, were the following: treatment of renal rejection (35% vs. 47%); renal allograft loss or death (9% vs. 12%); pancreas allograft loss or death (15% vs. 14%). Five MMF patients (7%) and four (5%) in the AZA group died. More MMF than AZA patients developed opportunistic infections (54% vs. 38%), but the pathogens did not differ. CONCLUSIONS: Trends for most efficacy parameters favored MMF over AZA, and time to renal allograft rejection or treatment failure was statistically significantly longer for MMF. The use of MMF in the treatment of SPK recipients is a useful advance.

Acute Disease↗

Clinical determinants of multiple acute rejection episodes in kidney transplant recipients.

BACKGROUND: Recipients with multiple (more than one) acute rejection (AR) episodes have significantly lower graft survival rates than those with no AR or only one treated episode. However, fewer than 50% of recipients treated for one AR episode will have another episode. METHODS: We studied recipients with at least one AR episode to determine whether any clinical features could identify risk factors for multiple AR. RESULTS: Between January 1, 1984, and June 30, 1997, a total of 1793 recipients underwent a kidney transplant at our institution. Of these, 354 were treated for one AR episode, 307 for more than one. By multivariate analysis, recipients at highest risk for multiple AR episodes were those with initial delayed or slow graft function (relative risk=1.5, P=0.05), those with initially severe AR (as judged by vascular involvement or steroid resistance), and those with an initial early AR episode (<6 months posttransplant). The remaining variables tested were not significant. Graft survival in recipients with more than one AR episode was significantly lower than in those with only one AR episode. Graft survival at 5 years posttransplant was 52.5% in recipients with more than one AR episode and 85.1% in recipients with one AR episode (P=0.0001). Chronic rejection as a cause of graft loss was significantly more common in recipients with more than one vs. only one AR episode (34.8% vs. 8.9%, P=0.001). CONCLUSION: Clinical features may be used to identify recipients at higher risk for multiple AR episodes. These recipients can then be targeted with more aggressive or novel immunosuppressive regimens in an attempt to reduce the likelihood of another AR episode.

Acute Disease↗

Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors?

BACKGROUND: Given the severe organ shortage and the documented superior results obtained with living (vs. cadaver) donor kidney transplants, we have adopted a very aggressive policy for the use of living donors. Currently, we make thorough attempts to locate a living related donor (LRD) or a living unrelated donor (LURD) before proceeding with a cadaver transplant. METHODS: We compared the results of our LURD versus LRD transplants to determine any significant difference in outcome. RESULTS: Between 1/1/84 and 6/30/98, we performed 711 adult kidney transplants with non-HLA-identical living donors. Of these, 595 procedures used LRDs and 116 used LURDs. Immunosuppression for both groups was cyclosporine-based, although LURD recipients received 5-7 days of induction therapy (antilymphocyte globulin or antithymocyte globulin), whereas LRD recipients did not. LURD recipients tended to be older, to have inferior HLA matching, and to have older donors than did the LRD recipients (all factors potentially associated with decreased graft survival). Short-term results, including initial graft function and incidence of acute rejection, were similar in the two groups. LURD recipients had a slightly higher incidence of cytomegalovirus disease (P=NS). We found no difference in patient and graft survival rates. However, the incidence of biopsy-proven chronic rejection was significantly lower among LURD recipients (16.7% for LRD recipients and 10.0% for LURD recipients at 5 years posttransplant; P=0.05). LRD recipients also had a greater incidence of late (>6 months posttransplant) acute rejection episodes than did the LURD recipients (8.6% vs. 2.6%, P=0.04). The exact reason for these findings is unknown. CONCLUSION: Although LURD recipients have poorer HLA matching and older donors, their patient and graft survival rates are equivalent to those of non-HLA-identical LRD recipients. The incidence of biopsy-proven chronic rejection is lower in LURD transplants. Given this finding and the superior results of living donor (vs. cadaver) transplants, a thorough search should be made for a living donor-LRD or LURD-before proceeding with a cadaver transplant.

Adult↗

Immunologic and nonimmunologic factors: different risks for cadaver and living donor transplantation.

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.

Acute Disease↗

Steroid withdrawal in pancreas transplant recipients.

BACKGROUND: Numerous studies of steroid withdrawal have been carried out in kidney and liver transplant recipients, but only a few in pancreas transplant recipients. Yet, pancreas transplant recipients could have significant long-term benefits from steroid withdrawal. METHODS: We performed a retrospective analysis to determine the feasibility of steroid withdrawal in pancreas transplant recipients. RESULTS: Of 360 recipients who underwent a pancreas transplant between January 1, 1994 and June 30, 1998, 14 attempted steroid withdrawal (12 simultaneous pancreas-kidney [SPK]; 2 pancreas transplant alone [PTA]). Reasons for steroid withdrawal were bone fractures (n = 3), psychiatric disorders (n = 2), severe acne (n = 1), recurrent infections (n = 4), and problems with hypercholesterolemia or hypertension (n = 4). All 14 were maintained on tacrolimus and mycophenolate mofetil (MMF) immunosuppression, except for 1 who was on tacrolimus and azathioprine (AZA). Of the 14 recipients, 11 had no episodes of acute rejection before steroid withdrawal. The remaining 3 had one or more acute rejection episodes. Of the 14 recipients, 10 (72%) currently remain off steroids (mean follow-up 18 months, range 5-51 months). However, 4 recipients have resumed steroids: 2 after an acute rejection episode (at 2 and 21 months post-withdrawal) and 2 because of leukopenia (WBC < 3000) and an inability to tolerate full-dose MMF. Steroid withdrawal was unsuccessful in both PTA recipients and in 2 of the 12 SPK recipients. All 14 recipients currently have a functioning pancreas graft. However, 1 of the SPK recipients, in whom steroid withdrawal failed, has developed chronic kidney rejection and is now back on hemodialysis awaiting a retransplant. CONCLUSION: Steroid withdrawal is possible in up to 70% of pancreas transplant recipients. Further studies are necessary to define ideal candidates for steroid withdrawal. Based on the results of this analysis, we have launched a prospective, randomized trial of steroid withdrawal in pancreas transplant recipients.

Adult↗

Should I accept this kidney?

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.

Adolescent↗

Renal transplantation for type II diabetic patients compared with type I diabetic patients and patients over 50 years old: a single-center experience.

INTRODUCTION: Transplantation of renal allografts for Type II diabetic patients has become increasingly common. Like Type I diabetics and patients over age 50, Type II diabetics are in a high-risk category for renal transplantation. Some investigators argue that the scarce resources of the valuable donor pool should not be allocated to these high-risk, older individuals with end-stage renal disease (ESRD) who often have significant comorbidity. We studied the outcome of renal transplantation for 90 Type II diabetics and compared it with the outcome for Type I diabetics and patients over age 50 with other primary diseases. METHODS: We conducted a retrospective review of data on all renal transplants performed at the University of Minnesota since September 1984 for Type II diabetics. We analyzed both patient and graft survival rates and compared them with the outcome for Type I diabetics and separately for all nondiabetics over age 50. We grouped recipients by donor source (living vs. cadaver) and age at transplant (< 50 vs. > 50). We studied reasons for graft loss, patient death, pre-operative morbidity, and post-operative complications. RESULTS: We found that recipient age and donor source did not affect outcome. Overall 5-yr patient survival for Type II diabetics was 61%; graft survival, 53%. Type II diabetics had significantly worse patient and graft survival than Type I diabetics and than nondiabetics over age 50. However, death-censored graft survival was not different between these groups, suggesting little difference in immunologic graft loss. CONCLUSIONS: Renal transplantation is a relatively safe, viable option for Type II diabetics with ESRD and significant comorbidity. Although their overall graft survival is less than for Type I diabetics and for nondiabetics over age 50, the immunologic graft failure rate is the same in all three groups.

Adult↗

Prolonged preservation increases surgical complications after pancreas transplants.

BACKGROUND: Prolonged preservation of the donor organ may result in delayed graft function or nonfunction after most organ transplants. We studied whether or not prolonged preservation increases surgical complications after pancreas transplants. METHODS: Between January 1, 1994, and September 30, 1998, a total of 294 recipients underwent cadaver pancreas transplants at our institution. Recipients were analyzed in 2 groups: those with pancreas preservation time < or = 20 hours (n = 211) versus > 20 hours (n = 83). RESULTS: Demographic data were similar between the 2 groups, except that mean donor age in the prolonged preservation group was significantly lower. Despite use of younger donors, prolonged preservation was associated with an increased incidence of surgical complications, most notably leaks, thrombosis, and wound infections. Grafts with prolonged preservation were more often noted by the transplant surgeon to be edematous after reperfusion, although the incidence of hyperamylasemia posttransplant did not differ between the 2 groups. Graft and patient survival rates also did not differ between the 2 groups. The incidence of early graft loss (< 3 months) was, however, higher in the prolonged preservation group (20.5% versus 9.0%, P = .04). CONCLUSIONS: Prolonged preservation of the donor organ increases the incidence of surgical complications after pancreas transplants. All attempts should be made to minimize preservation time, keeping it below 20 hours, if possible.

Adult↗

Surgical risks and outcome of pancreas retransplants.

BACKGROUND: The increased popularity of pancreas transplants has led to an increased number of potential candidates for retransplants after the initial graft has been lost to technical failure or rejection. We studied a group of recipients who underwent pancreas transplants at a single center to determine whether retransplant recipients were at higher risk of complications. METHODS: Between June 1, 1994, and Dec 31, 1997, a total of 213 pancreas transplants were performed at the University of Minnesota. Of these, 187 were primary transplants and 26 were retransplants. Demographically, the two groups were not significantly different. We analyzed and compared the two groups with respect to incidence of surgical complications, graft survival rates, and patient survival rates. RESULTS: Surgical complications such as bleeding and vascular thrombosis were slightly more common after retransplants, but this trend did not quite reach statistical significance. Infectious complications and leaks were equivalent between the two groups. The incidence of acute rejection was higher after retransplants (P =.02). At 3 years posttransplant, patient survival was no different between the two groups, but pancreas graft survival was lower after retransplants (P =.08). The incidence of early graft loss (by 6 months posttransplant) was significantly higher in retransplant recipients (27% vs 14%, P =.04). CONCLUSIONS: Pancreas retransplants can be performed with a minimal increase in surgical complications. However, graft survival after retransplants is slightly inferior to that after primary transplants, probably for both immunologic and nonimmunologic reasons. Retransplants can be offered to suitable candidates, but they may require more aggressive monitoring for rejection.

Adult↗

Decreased surgical risks of pancreas transplantation in the modern era.

OBJECTIVE: To document the decreased incidence of surgical complications after pancreas transplantation in recent times. SUMMARY BACKGROUND DATA: Compared with other abdominal transplants, pancreas transplants have historically had the highest incidence of surgical complications. However, over the past few years, the authors have noted a significant decrease in the incidence of surgical complications. METHODS: The authors studied the incidence of early (<3 months after transplant) surgical complications (e.g., relaparotomy, thrombosis, infections, leaks) after 580 pancreas transplants performed during a 12-year period. Patients were analyzed and compared in two time groups: era 1 (June 1, 1985, to April 30, 1994, n = 367) and era 2 (May 1, 1994, to June 30, 1997, n = 213). RESULTS: Overall, surgical complications were significantly reduced in era 2 compared with era 1. The relaparotomy rate decreased from 32.4% in era 1 to 18.8% in era 2. Significant risk factors for early relaparotomy were donor age older than 40 years and recipient obesity. Recipients with relaparotomy had significantly lower graft survival rates than those without relaparotomy, but patient survival rates were not significantly different. A major factor contributing to the lower relaparotomy rate in era 2 was a significant decrease in the incidence of graft thrombosis; the authors believe this lower incidence is due to the routine use of postoperative low-dose intravenous heparin and acetylsalicylic acid. The incidence of bleeding requiring relaparotomy did not differ between the two eras. Older donor age was the most significant risk factor for graft thrombosis. The incidence of intraabdominal infections significantly decreased between the two eras; this decrease may be due to improved prophylaxis regimens in the first postoperative week. CONCLUSIONS: Although a retrospective study has its limits, the results of this study, the largest single-center experience to date, show a significant decrease in the surgical risk associated with pancreas transplants. Reasons for this decrease are identification of donor and recipient risk factors, better prophylaxis regimens, refinements in surgical technique, and improved immunosuppressive regimens. These improved results suggest that more widespread application of pancreas transplantation is warranted.

Adult↗

5,000 kidney transplants--a single-center experience.

Between 6/1963 and 12/1998, 5,069 kidney transplants were done at the University of Minnesota. Of these, about half have been living donor, half cadaver. The majority (83%) have been primary transplants. Recipients were grouped in 6 eras based on changes in our immunosuppressive protocols--6/63-12/67 (n = 98); 1/68-7/79 (n = 1,188); 8/79-6/84 (n = 789); 7/84-9/90 (n = 1,006); 10/90-12/95 (n = 1,050; 1/96-12/98 (n = 718)--and their outcomes were compared. Recent eras contained a higher proportion of recipients aged > 50. Since the inception of the program, there has been a steady improvement in actuarial patient survival, graft survival, and death-censored graft survival. Short-term outcome for primary and retransplant recipients has been similar; however, long-term outcome seems worse for retransplant recipients. Importantly, acute rejection and infectious death have become rare causes of graft loss. Chronic rejection and death with function (most often due to a cardiovascular event) have become the predominant causes of graft loss. Recent changes in immunosuppressive protocols (Era VI) have included more aggressive attempts to maintain CsA levels > 150 ng/ml (by HPLC) in the first 3 months and the substitution of mycophenolate mofetil for azathioprine. As a result, the incidence of acute and chronic rejection has decreased and graft survival has improved.

Adolescent↗

Pancreas transplant outcomes for United States (US) cases reported to the United Network for Organ Sharing (UNOS) and non-US cases reported to the International Pancreas Transplant Registry (IPTR) as of October, 2000.

As of October 2000, > 15,000 pancreas transplant had been reported to the IPTR, > 11,000 in the US and > 4,000 outside the US. An era analysis of US cases from 1987-2000 showed a progressive improvement in outcome (p < 0.04), with pancreas transplant graft survival rates (GSRs) going from 72% to 82% at one year for SPK cases, from 52% to 74% for PAK cases, and from 47% to 76% for PTA cases. The improvements were due both to decreases in technical failure (TF) rates (overall from 16% to 7%) and immunological failure rates (going from 8% to 2% for SPK, from 27% to 6% for PAK, and from 37% to 12% for PTA cases). The proportion of recipients > 45 years old increased from 5% to 25%, and the improved outcomes encompassed the older patients as well. In patients > 45 years old, SPK pancreas GSRs at one year increased from 62% to 78% (p < 0.002). Pancreas GSRs were also similar for recipients reported to have Type 1 or Type 2 diabetes (at one year, 84% and 83%, respectively for 1996-2000 SPK transplants), the latter designated in 3% of the recipients. Contemporary pancreas transplant outcomes were calculated separately for 1996-2000 US and non-US cases. US patient survival rates at one year were > or = 94% in each recipient category, with one-year pancreas GSRs of 84% for SPK (n = 3,697), 76% for PAK (n = 696), and 71% for PTA (n = 300) (p = 0.0001). The immunological graft failure rates for 1996-2000 US SPK, PAK and PTA cases were 2%, 6%, and 8% at one year (p = 0.001). There was a progressive increase in the use of ED (as opposed to BD) for duct management, to > 50% for 1996-2000 US SPK transplants. Approximately 20% of US SPK ED transplants had venous drainage via the portal system. Pancreas GSRs were not significantly different for 1996-2000 ED (n = 1,940) and BD (n = 1,541) US SPK transplants (83% and 84%, respectively, at one year), nor was there a difference in pancreas GSRs for systemic (n = 1,509) versus portal (n = 411) venous drained ED SPK transplants (83% for both at one year). Kidney GSRs were also not significantly different for ED versus BD US SPK cases, 93% versus 91% at one year (p = 0.13). Duct management did matter for solitary (PAK and PTA) pancreas transplants (P < or = 0.07). Pancreas GSRs for PAK recipients were 77% at one year for BD (n = 359) versus 67% for ED (n = 306) US transplants; for PTA 75% (n = 174) versus 63%. However, BD transplants were associated with a 12% conversion rate to ED by 2 years after transplantation. Analyses of outcome by immunosuppression for US cases showed pancreas GSRs ranged from 77% to 88% at one year, but were highest in SPK recipients given anti-T-cell agents for induction and CSA-MMF for maintenance immunosuppression. For PAK and PTA recipients, those given anti-T-cell agents for induction and TAC-MMF for maintenance immunosuppression had the highest GSRs: 78% and 78%, respectively, at one year for BD pancreas transplants (vs. 85% in BD SPK recipients similarly immunosuppressed, P > 0.08). In regard to non-US cases, the overwhelming majority were in the SPK category (n = 676 for 1996-2000), with a one-year pancreas GSR of 84%, not significantly different than for US cases. In summary, pancreas transplant graft survival rates were > 70% in the solitary (PAK and PTA) and > 80% in SPK recipients during the last 4 years of the 20th century. These outcomes culminate a third of a century of application for the treatment of diabetes mellitus.

Adult↗

Immunologic factors: the major risk for decreased long-term renal allograft survival.

BACKGROUND: Both antigen-dependent (immunologic) and non-antigen-dependent (nonimmunologic) factors have been implicated in long-term renal allograft loss. Differentiating between these two factors is important because prevention strategies differ. METHODS: To isolate the importance of these 2 factors, we studied long-term actuarial graft survival in a cohort of adult kidney recipients who underwent transplants at a single institution between January 1, 1984 and October 31, 1998. Excluded were recipients with graft loss as a result of death with function, technical failure, primary nonfunction, and recurrent disease, leaving 1587 recipients (757 cadaver [CAD], 830 living donor [LD]) who would be at risk for graft loss secondary to both immunologic and nonimmunologic factors. These recipients were analyzed in the following 2 groups: those treated for a previous episode of acute rejection (AR) (Group1; n = 588; 328 CAD, 260 LD) and those with no AR (Group 2: n = 999; 429 CAD, 570 LD). Actuarial graft survival and causes of graft loss were determined for each group. Presumably, graft loss in Group 1 would be caused by immunologic and nonimmunologic factors; graft loss in Group 2 would be caused primarily by nonimmunologic factors. RESULTS: The 10-year graft survival rate (censored for death with function, technical failure, primary nonfunction, and recurrent disease) in Group 2 was 91%. In contrast, the 10-year graft survival rate in Group 1 was 45% (P<0.001 vs. Group 2). Causes of graft loss in Group 2 were chronic rejection in 1.8% (3.0% CAD, 0.9% LD), de novo disease, 0.4%; sepsis, 0.2%; discontinuation of immunosuppressive therapy, 0.3%; and unknown, 0.6%. In contrast, 23.8% (29.9% CAD, 16.2% LD) of recipients in Group 1 had graft loss caused by chronic rejection (P = 0.001 vs. Group 2). CONCLUSIONS: This very low incidence of chronic rejection in recipients without previous AR suggests that immunologic factors are the main determinants of long-term kidney transplant outcome; nonimmunologic factors in isolation may have only a minimal impact on long-term graft survival.

Adult↗

Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients.

BACKGROUND: It has long been suggested that cytomegalovirus (CMV) disease plays a role in the pathogenesis of chronic rejection (CR). However, its role has been difficult to prove, given the strong association between acute rejection and CMV, and the even stronger association between acute rejection and CR. To try to isolate the relative contribution of CMV infection in the pathogenesis of CR, we used multivariate techniques to examine risk factors for CR, including CMV disease. METHODS: Our study population consisted of adult recipients of a first kidney graft who underwent transplantation at a single center between 1/1/85 and 6/30/97 (n = 1339). RESULTS: Multivariate analysis using time to CR as the dependent variable demonstrated acute rejection to be the strongest risk factor (relative risk [RR] = 17.8, P = 0.0001), followed by older donor age (RR = 1.46, P = 0.01). The presence of CMV disease showed a trend toward increased risk for CR (RR = 1.30, P = 0.10), although the association was not as strong as with the other two variables. Comparing only those recipients with acute rejection and CMV disease versus those with acute rejection but no CMV disease, the relative risk of developing CR was 1.37 times higher in the former group. Recipients with acute rejection and CMV developed CR sooner and with a higher incidence versus those with acute rejection but no CMV (P = 0.002). It is interesting, however, that CMV disease was only a risk factor for CR in the presence of acute rejection. Recipients with no acute rejection and CMV disease did not have a higher incidence of CR versus those with no acute rejection and no CMV (P = NS). CONCLUSION: CMV disease seems to play some role in the pathogenesis of CR but only in the presence of acute rejection. Reasons may include (i) the inability to adequately treat acute rejection due to the presence of CMV disease or (ii) the increased virulence of latent CMV virus in recipients being treated for acute rejection. Our data may suggest a role for more aggressive prophylaxis against CMV disease, especially at the time of treatment for acute rejection.

Acute Disease↗