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S J Knechtle

Publications and source records attributed to S J Knechtle.

At least 73 records · Page 4Linked to original sources
PubMed1997

Increased beta 2-microglobulin (B2M) is useful in the detection of post-transplant lymphoproliferative disease (PTLD).

This study examines whether changes in beta 2-microglobulin (B2M) serum levels are useful in the early detection of post-transplant lymphoproliferative disease (PTLD). Serum B2M is monitored daily post-transplant at our center as a marker of change in lymphocyte activation. We identified 16 cases (16/1359; 1.2%) of PTLD from among 1359 kidney and kidney-pancreas transplants. Those with CNS lymphoma (two patients) and titer change only (one) were not included in this review. Thirteen patients had serum titer and clinical evidence of EBV activity; 12 of these patients had histological evidence of PTLD (lymph node 6, kidney 3, and generalized disease 3). Three patients died with disseminated PTLD infection. Nine are alive but only two have the original transplant kidney. All patients received quadruple immunosuppression for induction, and 11 were subsequently treated with OKT3 or ALG for rejection. The mean number of days of induction ALG therapy was 14.8 d (20 mg/kg/d). The mean number of days of OKT3 therapy for rejection was 14.4 d (5 mg/d). During rejection the highest mean creatinine level was 6.8 mg/dL, and the highest mean B2M level was 16.4. With PTLD, the highest mean creatinine level was 7.0 mg/dL and the highest mean B2M level was 32.3 mg/L. The difference in creatinine levels was not significant, but the difference in B2M levels was significant (p < 0.01). We conclude that B2M levels are useful markers in differentiating rejection from PTLD.

Adult↗
PubMed1997

Clostridial infection of a liver transplant treated with retransplantation.

Clostridial infection of a liver transplant is reported and was treated successfully with immediate retransplantation and antibiotics. This strategy may salvage patients who otherwise have a fulminant course and certain death. This case supports the general principle that infection localized to the liver can be successfully treated with retransplantation when appropriate.

Adult↗
PubMed1997

Advances in pancreas transplantation: the University of Wisconsin experience.

The data show that with careful surgical technique, modern immunosuppression with MMF and FK506, and pancreatic allograft biopsy, it should be possible to achieve: 1) a low rate of technical complications, 2) improved long-term graft survival, particularly in solitary pancreas recipients improving the risk/benefit ratio of this option for nonuremic diabetics, 3) a high safety profile with combined MMF and FK506 immunosuppression, 4) safe transplantation using enteric drainage without increased risk of rejection, infection or graft loss, and 5) successful pancreas transplantation without induction therapy.

Adolescent↗
PubMed1996

Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys: HLA-DR3 as a risk factor for the development of posttransplant hepatitis.

BACKGROUND: Exposure to hepatitis C virus (HCV) and subsequent infection after renal transplantation lead to significant clinical hepatitis in approximately 50% of graft recipients. METHODS: One hundred thirty-two consecutive renal allotransplant patients, who underwent transplantation of kidneys from HCV-positive cadaveric donors, were studied to investigate the relationship between donor and recipient HLA type and the risk of developing clinical hepatitis. Specific attention was directed toward the DR3 and DR4 alleles, as these had previously been associated with worse prognoses in autoimmune and viral hepatitis. RESULTS: Overall, 42% of patients receiving kidneys from donors seropositive for HCV developed clinical hepatitis. This was unrelated to preoperative recipient HCV serum reactivity (P=0.65). Patients receiving kidneys from seropositive donors with HCV RNA as detected by PCR were more likely to develop hepatitis than those receiving kidneys from PCR-negative donors (56% vs. 11%; P=0.005). The presence of the DR3 allele was associated with a significant risk of clinical hepatitis (P=0.025); 80% of DR3-positive recipients (n=34) progressed to hepatitis compared with 42% of DR3-negative patients. No other recipient HLA type was significantly related to prognosis. All patients receiving a donated kidney that expressed the B41 allele developed hepatitis, compared with 55% of recipients of non-B41 grafts (P=0.039). No association between the development of clinical hepatitis and HLA compatibility was found. CONCLUSIONS: These results suggest that both HLA type and viral presence as assayed by polymerase chain reaction, influence the risk of disease progression after transplantation of HCV-positive kidneys. Application of these associations may decrease the relative risk of a recipient contracting HCV hepatitis after cadaveric renal transplantation.

Alleles↗
PubMed1996

Adenovirus-mediated gene transfer into rat cardiac allografts. Comparison of direct injection and perfusion.

With the ultimate goal of modulating the host immune response in organ transplantation, gene therapy studies have demonstrated that direct plasmid DNA injection into transplanted myocardium can result in detectable levels of transgene expression. However, the restricted distribution and low level of transgene expression evident in these studies have limited its application. Recently, replication-defective adenovirus vectors have been shown to be an efficient gene-transfer vehicle in vivo whose infection does not require target-cell proliferation. In the present study, adenovirus vectors encoding reporter genes were delivered into transplanted hearts by either direct injection into the myocardium or perfusion via aorta of the donor hearts. The efficacy and stability of the transgene expression by perfusion and by direct injection were examined and compared. Using the adenovirus vector encoding the firefly luciferase gene, we found that a higher level of transgene expression was achieved by direct injection, but that more evenly distributed transgene expression was observed in hearts perfused with viral vector. These results were further confirmed by 5-bromo-4-chloro-3-indolyl-beta-d-galactoside histochemical staining of another adenoviral vector encoding beta-galactosidase. The transgene expression was not stable and decreased within 1 month with either delivery method. Nevertheless, these results indicate that adenovirus-mediated gene transfer can result in short-term expression of the gene throughout the heart and may be useful as a gene vector in organ transplantation.

Adenoviridae↗
PubMed1996

Determinants of graft survival after renal transplantation.

We studied multiple determinants of graft survival at a single center and the effects of nonimmunologic graft loss on transplant survival. This retrospective study examined the results of 589 cadaver donor transplants performed between 1986 and 1992. Graft survival rates were calculated using Kaplan-Meier estimates for both overall graft survival (all causes of graft loss) and immunologic graft survival (function lost due to acute or chronic rejection and noncompliance). Cadaver graft survival was significantly poorer with an increasing degree of DR mismatch (P=0.02). An analysis of pretransplant variables showed graft loss risk was highest with greater DR mismatches, two B-antigen mismatch, higher donor serum creatinine, and younger recipient age. After transplantation, acute rejection was the most significant factor associated with long-term graft survival. Our data demonstrate a significant advantage for zero DR and one DR mismatch cadaver donor transplants, with excellent immunologic graft survival. This study suggests that a combination of immediate graft function, prevention of acute rejection by appropriate early immunosuppressive therapy, and acceptable DR match enhances cadaveric graft survival.

Adult↗
PubMed1996

Immunosuppressive effects of an HLA class I-derived peptide in a rat cardiac allograft model.

B7.75-84, a 10-amino-acid peptide derived from the HLA-B7 molecule, prolongs rat heterotopic cardiac allograft survival time (GST) when used with cyclosporine in the Lewis-to-ACI strain combination. We evaluated the ability of B7.75-84 to prolong GST in other strain combinations without cyclosporine and studied the effect of B7.75-84 on the immune response in the Wistar-Furth (WF)-to-ACI strain combination. GST was markedly prolonged in most low-responder (ACI) recipients but only slightly prolonged in the high-responder (Lewis) recipient. Cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) limiting dilution assays (LDA) were performed 10 days after cardiac allografts from WF donors were placed in ACI recipients treated with B7.75-84. HTL-LDA assays at 10 days posttransplant showed a slight decrease in HTL precursor frequency and a decrease in their IL-2 production in B7.75-84 treated recipients with prolonged GST in response to donor antigen as well as third-party (Lewis) antigen. CTL-LDA assays at day 10 showed no difference in CTL precursor frequency among treated recipients but did show a significant decrease in CTL killing activity against donor cells in recipients with prolonged GST. No significant difference in CTL killing activity was seen against third- party cells. Antibody analysis was performed at day 8 in treated recipients. Serum from B7.75-84-treated recipients with prolonged graft survival generally showed no detectable IgG antibody response against donor MHC class I antigen. All B7.75-84 treated recipients showed a strong IgM response against donor antigen regardless of allograft outcome. Our results suggest that the immunosuppressive effect of B7.75-84 in rats is greater using a low-responder RT1 haplotype. Furthermore, B7.75-84 induces a nonspecific decrease in HTL function while producing a donor-specific decrease in CTL function and a diminished antidonor MHC class I IgG response.

Animals↗
PubMed1996

Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3.

PURPOSE: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. METHODS AND MATERIALS: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. RESULTS: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months)> CONCLUSION: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant.

Cohort Studies↗
PubMed1996

The influence of native nephrectomy on the incidence of recurrent disease following renal transplantation for primary glomerulonephritis.

Factors influencing the incidence of recurrent glomerulonephritis following renal transplantation are poorly understood. Bilateral pretransplant native nephrectomy has been advocated to reduce the likelihood of recurrence after renal transplant. However, there is significant morbidity of native nephrectomy in the uremic population. Therefore, we sought to determine the effect of pretransplant native nephrectomy on the incidence of recurrent primary glomerulonephritis and the attendant risk of graft failure due to recurrent disease. Three hundred sixty-four consecutive cadaveric (n = 214), living-related (n = 137), and living-unrelated (n = 13) renal transplants were performed in 319 patients with a diagnosis of primary glomerulonephritis. Specific diagnoses included were focal segmental glomerulosclerosis (FSGS), rapidly progressive glomerulonephritis/idiopathic crescentic glomerulonephritis (RPGN/ICG), IgA nephropathy (IgA), mesangioproliferative glomerulonephritis, type I and II (MPG), anti-glomerular basement membrane nephritis (anti-GBM), and membranous glomerulonephritis (MGN). Rates of recurrence and graft loss were compared between patients treated with bilateral native nephrectomy (n = 61) and those who were not (n = 303). Bilateral nephrectomy did not prevent or delay the onset of recurrent glomerulonephritis in the renal allograft. In fact, there was a significantly increased five- and ten-year risk of recurrence in patients undergoing pretransplant nephrectomy vs. no nephrectomy (25.2% and 42% vs. 13.9% and 19.4%, P < 0.02, respectively). The increased rate of recurrence was evident in the CAD/LUD recipients, but not in recipients of LRD transplants. Of the specific diseases, FSGS and MGN recurred more commonly (20.2% and 20.3%, respectively). A detrimental effect of pretransplant nephrectomy on recurrence rates and incidence of graft loss due to recurrent disease independent of other variables could be demonstrated only for FSGS patients. Based on these findings, we no longer recommend native nephrectomy in the prospective renal transplant recipient at high risk for developing recurrent glomerulonephritis.

Adolescent↗
PubMed1996

Impact of improving immunosuppressive treatment on outcome in cadaveric kidney transplantation.

BACKGROUND: Since the advent of cyclosporine-based immunosuppression for cadaveric kidney transplants in 1983, several changes have been made in immunosuppressive management at the University of Wisconsin. Since 1986, OKT3 has been available to treat steroid-resistant rejection; since 1992, OKT3 has been used as an induction agent replacing antilymphocyte globulin; and since 1993, mycophenolate mofetil has been used in 104 patients. METHODS: The impact of different immunosuppressive strategies on overall and immunologic graft survival (defined as graft loss caused by rejection) was evaluated in 1210 primary cadaveric renal transplants at the University of Wisconsin. Covariables, including degree of human leukocyte antigen matching, age, gender, cause of kidney failure, and early graft dysfunction, were evaluated. The series was subdivided into four eras according to immunosuppressive regimen, and the results were analyzed by era. RESULTS: Our principal findings are that immunologic graft survival has improved significantly during this series whereas overall graft survival has not. Mycophenolate was associated with a significant decrease in acute rejection. For a given patient, graft loss from rejection becomes less likely over time. Late rejection poses a greater risk than early rejection for graft loss. CONCLUSIONS: Improving outcomes may be related to improving immunosuppressive treatment, increasing degree of human leukocyte antigen matching, and better early graft function.

Adult↗
PubMed1996

Risk factors for renal allograft loss in patients with systemic lupus erythematosus.

Controversy exists regarding the risk factors for renal allograft loss in patients with systemic lupus erythematosus (SLE). This study is a retrospective evaluation of each of these independent risk factors in 80 renal transplants for ESRD secondary to SLE done at our institution between 1971 and 1994. Our entire non-diabetic cohort of 1,966 renal transplants is used as a comparison group. Our results showed equivalent graft survival rates between lupus patients and the cohort at 1, 5 and 10 years (P = 0.56). However, an analysis of cyclosporine-era cadaver grafts revealed that the lupus group had poorer 5-year graft survival than the cohort (41% vs. 71%, P = 0.02). Evaluation of cyclosporine-era lupus graft survival showed significantly improved outcome in living-related lupus recipients over cadaver grafts at five years (89% vs. 41%, P = 0.003). The majority of grafts lost in the lupus cadaver recipients were due to chronic rejection. Rejection was increased in lupus recipients: 69% of lupus patients experienced rejection in the first year compared to 58% of controls (P = 0.01). Stratified for age, sex, race and cyclosporine use, this difference remained significant (P = 0.003, relative risk 1.7). Nephrectomy, splenectomy and 3 to 6 months of pretransplant dialysis did not improve graft survival. A dialysis duration of greater than 25 months predicted worse graft survival (P = 0.01). Among lupus patients, PRA did not correlate with graft outcome (P = 0.5), and HLA-identical cadaver grafts had improved outcomes compared to cadaver grafts. We conclude that acute and chronic rejection are the major risk factors for graft loss in lupus patients. The superior outcome of living-related over cadaver grafts in lupus patients suggests an increased role for living-related grafts. Pretransplant dialysis, nephrectomy and splenectomy are not indicated.

Adult↗
PubMed1996

Preliminary experience with split liver transplantation.

BACKGROUND: The purpose of split liver transplantation is to alleviate the organ shortage for patients with end-stage liver disease. The procedure, however, has not gained wide acceptance. This is related not only to the complexity of the procedure but also to poorer results and the complications reported to be associated with the technique. STUDY DESIGN: We report 12 split liver transplantation procedures, seven in children and five in adults. Selection criteria were the same as those for whole-size liver transplantation. Patient and graft survival as well as complications were analyzed. Results were analyzed by Wilcoxon life tables. RESULTS: Patient and graft survival rates are 91.6 and 75 percent, respectively. One patient died at 2.5 months after transplantation because of lymphoproliferative disease. Another had acute vanishing bile duct syndrome and required retransplantation at 1.5 months. One patient had retransplantation because of hepatic artery thrombosis. Bile leaks occurred in two patients and hemothorax in one patient. CONCLUSIONS: Our results indicate that split liver transplantation has become a more acceptable method of hepatic transplantation and should be encouraged. Several guidelines can enhance success rates.

Adult↗