Biomedical subjects
Publications and source records attributed to D E Sutherland.
Either organ (pancreas or kidney) from a single donor in a single recipient can be discordantly lost from rejection. One can be totally rejected with the other totally normal, or the other may function within the context of chronic rejection. The pancreas is more likely to function with the kidney being rejected than vice versa.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Nephrotoxicity remains a concern for patients on long-term cyclosporine. We have previously reported on renal function in a cohort of kidney transplant recipients followed up to 10 years posttransplant. The current study extends the analysis to 12 years. We find no evidence of cyclosporine-induced renal failure.
As of 1995, more than 7,500 pancreas transplants had been reported to the International Pancreas Transplant Registry. More than 5,300 were performed in the United States, including more than 4,000 since the inception of the UNOS Registry in October, 1987. The bladder drainage (BD) technique has been the most widely used duct management technique since 1987 with 93% of all cases. In the overall analysis of US BID cadaveric pancreas transplants reported to the registry, patient survival and pancreas functional graft survival rates were 91% and 75% respectively, at one year, 88% and 72% at 2 years, and 85% and 67% at 3 years. When the 1987-95 US data for primary BID cases was analyzed according to the three major recipient categories [simultaneous pancreas/kidney transplants (SPK) (n=3,539); pancreas after kidney transplants (PAK) (n=238); and pancreas transplants alone (PTA) (n=175)], patient survival rates were no different (91%, 92% and 91% at one year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (78%, 56%, and 55%, at one year, respectively). In the SPK group, kidney graft survival rates at one year were 86%. An improvement of the graft survival could be shown over the analyzed time period for all categories. Outcomes were also compared according to whether induction immunotherapy in recipients included ALG/ATG/ATS, OKT3 or neither. In the primary SPK category, patients who received OKT3 (n=1,416) showed the best outcome with one-year graft survival rates of 83% followed by ALG/ATG/ATS (n=1,559) with 78%. Patients that received neither (n=410) had a significantly lower graft survival rate. In the primary PAK category, the use of OKT3 (n=49) was associated with lower graft survival rates than when ALG/ATG/ATS (n=143) or neither (n=40) were given, 51%, 66%, and 55% at one-year, respectively. In the PTA category, the use of ALG/ATG/ATS (n=93) was associated with significantly higher graft survival rates than when OKT3 (n=62) or neither (n=9) were used, being 63%, 58%, and none, respectively, at one-year. No negative impact of longer preservation time could be found in the univariate analysis. The effect of HLA-A, B and DR mismatching on outcome for primary US cases was also determined. Again the results differed according to recipient category. For SPK cases, there was only a beneficial effect of a perfect 6 antigen match (n=21) compared to 1 and 2-6 mismatches being 85%, 73% and 78% at one-year. In the primary PAK category, graft survival rates were significantly higher in those mismatched for 0 (n=6) and one (n=25) than for 2-6 (n=195) HLA antigens, being 100%, 76% and 58% at one year. In the primary PTA category there were no zero mismatch, technically successful cases. One-year graft survival rates were 70% (n=10) for the category with one mismatch and 55% (n=157) in the 2-6 antigen mismatch group. Cox multivariate analyses of the US data base showed that, overall, recipient category was the most significant factor (relative risk for graft loss being significantly lower for SPK than for PAK and PTA cases). Other variables also had an impact on results depending on the recipient category. Recipient age has an impact on patient survival as well as graft survival. It was most influential in the SPK and PAK category, but an effect was not seen in the PTA category. In both the PAK and PTA categories, minimizing HLA mismatches was associated with a significantly lower risk for graft loss. In the SPK and PTA category, anti-T-cell therapy significantly lowered the risk of graft loss. In the PAK and SPK category the transplant outcome improved significantly over the analyzed time period. Patient survival also improved overtime.
Organ transplantation is a viable treatment for individuals whose quality of life is significantly impaired. There has been a dramatic increase in the number of whole organ transplants being performed over the past few years; and although somewhat limited by donor availability, these numbers have continued to increase as success rates improve and more medical centers perform them. The number of solid organ transplants performed throughout the world has grown from 35,628 (1980-1990) to 285,561 (1989-1991). The number of patients on the waiting list for organs has increased by 59.4 percent from 1988 to 1993. As this patient population grows, the community-based dental practitioner will be faced with a special set of concerns. Understanding the diverse precautions for treatment of pre- and post-organ transplant patients will help the practitioner adequately treat the dental needs of this patients population.
Recipient selection criteria for pancreas (Px) transplantation differ among centers, based on perceived recipient risk factors, and their validity has not been determined. At the University of Minnesota we have been very liberal in accepting patients for Tx, some of whom have risk factors cited as exclusion criteria by other centers, giving us the opportunity to determine, retrospectively, the impact of their presence on outcome. Between July 1986 and March 1993, we performed 319 bladder-drained cadaver Px Txs at the University of Minnesota, 166 simultaneous with a kidney (SPK), 68 after a kidney (PAK), and 85 alone (PTA). To determine which putative "risk factors" influence patient and graft survival, we used uni- and multivariate (Cox regression) analyses to assess the impact of recipient category, duration of diabetes, and age at onset and at Tx; presence of pre-Tx cardiac (CD) disease (myocardial infarction, bypass, angioplasty), peripheral vascular disease (PVD) (stroke, bypass, angioplasty, amputation); blindness, hypertension, and excess weight; and of Px re-Txs. The incidences of all risk factors except re-Tx were significantly higher in SPK than PTA recipients. Px re-Txs comprised 40% of PAK, 26% of PTA, and 10% of SPK cases (P < 0.0001). Duration of diabetes correlated (P < or = 0.01) with all risk factors but one (hypertension). Recipient age correlated (P < or = 0.01) with CD, blindness, duration of diabetes, and age at onset of diabetes; CD risk factors correlated (P < 0.015) with hypertension and PVD. Recipient age (> or = 45) influenced the technical failure rate only in SPK recipients, with a relative risk (RR) of 2.13 (P = 0.08). Recipient age influenced Px graft and patient survival rates in both SPK and PAK recipients; for those > or = 45, the RR of graft loss was 1.73 and 1.76, respectively (P < or = 0.25), and the RR for ultimately dying was 3.07 in PAK (P = 0.02) and 5.86 in SPK (P = 0.17) recipients. SPK recipients with CD factors were at higher risk to ultimately die (RR = 3.78, P = 0.009), independent of age. Px re-Txs were not at higher risk to fail in PTA, but were in PAK recipients (RR = 1.86, P = 0.09); the risk for technical failure was higher for re-Txs only in SPK recipients (RR = 2.11, P = 0.24). Blindness, hypertension, PVD, and duration of diabetes did not negatively influence patient and graft outcome in any recipient category.(ABSTRACT TRUNCATED AT 400 WORDS)
Products of inflammation, such as interleukin-1 beta (IL-1 beta) and nitric oxide (NO), may impair early function of pancreatic islet grafts. In in vitro studies, freshly isolated rat islets of Langerhans cultured for 24 hr (10 islets/well) in the presence of 20 IU/ml of IL-1 beta released 57% less insulin (mean +/- S.E. of 151 +/- 61 microU) on the average than control (385 +/- 89 microU) cultures (n = 9, P = 0.08). Nitrite levels in the medium (indirect measure of NO) after islets were cultured for a 24-hr period were nearly 3-fold greater in IL-1 beta-exposed islets than control islet cultures (5.8 +/- 1.0 microM vs. 2.2 +/- 0.3 microM, P = 0.03). Production of nitrite by islet cells in the presence of IL-1 beta was inhibited in cultures also containing 2 mM L-NG-monomethyl-Arginine (L-NMMA) (3.4 +/- 0.4 microM, n = 9, P = 0.09 vs. control). When islets were maintained for 1 hr in 30 mg/dl glucose followed by 300 mg/dl for 1 hr, insulin release (stimulated) increased 6-fold (from 7 +/- 2 to 45 +/- 11 microU) in control cultures but only 3-fold (from 4 +/- 2 to 12 +/- 4 microU) in IL-1 beta-exposed cultures (n = 9, P = .01). Addition of 2 mM L-NMMA to islet cultures in the presence of IL-1 beta (20 IU/ml) (n = 9) restored insulin release to normal (from 6 +/- 2 to 38 +/- 9 microU, P > or = 0.6), suggesting that NO mediates the inhibitory effect of IL-1 beta on beta-cell function. In in vivo studies, rats with streptozotocin-induced diabetes (blood glucose > 400 mg/dl) received minimal (750 hand-picked islets) intraportal beta cell mass isografts with (n = 5) or without (n = 9) treatment with 100 mg/7 days of L-NMMA from 3 days before transplantation to 4 days after transplantation (POD -3 to +4). L-NMMA-treated rats became euglycemic (glucose < 200 mg/dl) earlier than nontreated rats (mean +/- SD of 6.4 +/- 2.5 vs. 16.7 +/- 4.7 days posttransplant, P = 0.001). These findings support the hypothesis that NO is a mediator of beta cell dysfunction after intraportal transplantation of freshly isolated islets of Langerhans.
Clinical observations suggest that recipients of multiorgan transplants from the same donor can have disparate immunological reactions to each organ. We studied this phenomenon in 36 diabetic (streptozotocin-induced), bilaterally nephrectomized, immunosuppressed (cyclosporine, azathioprine, prednisone) pig recipients of simultaneous (same donor) pancreas (bladder drained) and kidney allografts by grading the histological intensity of rejection in biopsies of each organ at defined intervals posttransplant. Graft function was monitored by plasma glucose (PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr) for the kidney. Interstitial rejection was graded as absent, mild, moderate, and severe in, respectively, 8%, 25%, 42%, and 25% of pancreas vs. 4%, 12%, 27%, and 57% of kidney biopsies at 1 week; and 0%, 43%, 29%, and 29% of pancreases vs. 10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of grades was similar in the two organs (P > 0.1), the grade of rejection for each pair at 1 week (n = 24) was discordant in 75% (42% differed by one and 33% by > or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2 grades). The inability to use the severity of interstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interstitial rejection at one week, the corresponding kidney showed moderate or severe rejection, and for the 1 kidney without rejection the corresponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution for the pancreas (57%, 30%, 9%, 4%) vs. kidney (50%, 38%, 0%, 12%) at 1 week, and at 2 weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11 for the kidney) (P > or = 0.64). However, the grading of vascular rejection in organ pairs was dyssynchronous in 54% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No vascular rejection in the pancreas with rejection in the kidney was seen in 5 pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%).(ABSTRACT TRUNCATED AT 400 WORDS)
Living unrelated donor (LURD) transplants have immunologic barriers similar to cadaver transplants, yet the outcome is better (1-year graft survival = 96%). One advantage of LURD transplants is that, with the extremely short preservation time, the kidney functions immediately. We studied whether the quality of initial renal function affects the outcome of primary cadaver transplants. We divided 301 non-6-antigen-matched recipients transplanted between 1/1/86 and 8/1/92--who had no graft loss due to hyperacute rejection, primary nonfunction, or technical reasons--into 5 groups based on the quality of initial renal function (serum creatinine level in the first week). We determined patient and graft survival rates for each group. We found that the quality of initial function had a significant effect on patient and graft survival rates. Recipients whose serum creatinine level was < 3 mg/dl on posttransplant day 5 (groups 1 and 2) had better patient and graft survival than either those whose serum creatinine level was > 3 mg/dl on day 7 (group 4) or those who required dialysis (group 5). Because some early dysfunction may be immunologic, we reanalyzed the data excluding patients with percent reactive antibody > or = 15; the quality of initial function in this group had a significant impact on outcome. Similarly, when patients with graft loss due to "death with function" were excluded, the quality of initial function had a significant impact on survival rates. We conclude that the quality of early posttransplant function is an important predictor of long-term outcome. Cadaver recipients with immediate good function have outcomes similar to living donor recipients. Our data suggest that increased effort should be made to improve immediate posttransplant function.
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The waiting list for cadaver kidney transplantation continues to grow. Yet there has been little increase in the number of living-donor transplants. At many centers, willing relatives are turned down as potential donors because of poor HLA ABDR matching with the recipient. It has been our policy to accept the 0-haplotype-match (0-HTM) living-related donor. We studied long-term (6-year) outcome of 0-HTM transplants compared with the outcome of transplants from 1- and 2-HTM recipients and from cadaver donors. Since 1984, 352 adults have received primary living-related renal transplants, and had a minimum of 1 year of follow-up: 92 2-HTM, 216 1-HTM, and 44 0-HTM. In the same period and with the same follow-up, 362 adults have received primary cadaver (CAD) renal transplants. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone (triple therapy) for living-donor and sequential therapy for CAD recipients. ABDR match (mean +/- SD) for 0 HTM was 1.3 +/- 8; CAD, 2.0 +/- 1.6; % peak panel-reactive antibodies (PRA) for 0 HTM was 1.2 +/- 5.3; 1 HTM, 6.7 +/- 20; 2 HTM, 7.5 +/- 21; CAD, 15.5 +/- 30. The percentage of PRA at the time of transplant for 0 HTM was .7 +/- 4.4; 1 HTM, 4.1 +/- 1.6; 2 HTM, 6 +/- 18; CAD, 7.2 +/- 20. While the number of ABDR matches was significantly fewer for 0 HTM than for the other groups, the % PRA at transplant and the peak % PRA were less in the 0-HTM group. Other demographics were not significantly different. Patient survival was significantly lower in the CAD group vs. 2-HTM recipients (P < .05). The living-related grafts had significantly greater survival than the CAD grafts (P < .05), but there was no significant difference between 0-, 1-, and 2-HTM graft survival. The most common causes of graft loss in all groups were death and chronic rejection. In our experience, the long-term graft survivals of 0-HTM and 1-HTM transplants are the same, and both are superior to CAD results, using 0-HTM living-related donor transplants should be continued and encouraged.