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John D Pirsch

Publications and source records attributed to John D Pirsch.

At least 19 recordsLinked to original sources
PubMed2006

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation.

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.

Adult↗
PubMed2005

Simultaneous pancreas-kidney transplantation from donation after cardiac death: successful long-term outcomes.

OBJECTIVE: The outcomes of simultaneous pancreas-kidney (SPK) transplantation with donor organs procured from donation after cardiac death (DCD) are compared with transplants performed with donor organs recovered from donation after brain death (DBD). SUMMARY BACKGROUND DATA: Concerns exist regarding the utilization of pancreata obtained from DCD donors. While it is known that DCD kidneys will have a higher rate of DGF, long-term functional graft survival data for DCD pancreata have not been reported. METHODS: A retrospective review of all DCD SPK transplants performed at a single center was undertaken. RESULTS: Patient, pancreas, and kidney survival at 5 years were similar between DCD and DBD organs. Pancreas function and outcomes were indistinguishable between the 2 modes of procurement. As expected, the DCD kidneys had an elevated rate of DGF, which had no significant long-term clinical impact. CONCLUSION: SPK transplantation using selected DCD donors is a safe and viable method to expand the organ pool for transplantation.

Adult↗
PubMed2005

Influence of kidney function to the impact of acute rejection on long-term kidney transplant survival.

In kidney transplantation, timing of an initial acute rejection (AR) is correlated with a variable risk of graft loss. However, it is unknown whether the increased risk for graft loss because of AR is conditioned by impaired graft function. A total of 730 cadaveric kidney transplant recipients were retrospectively evaluated from 1994 to 2001. When AR occurred, the risk ratio (RR) for graft loss was strongly time-dependent and increased, the later the rejection episode occurred. Compared with the reference group (no rejection) having an AR within 0-30, 31-365, or >365 days post-transplant conferred a 3.1-, 9.1- and 49.3-fold risk for subsequent graft loss (P < 0.001). By including serum creatinine as an indicator for graft function at the time of rejection RR decreased to 2.4-, 7.1- and 21.8-fold, but remained still significant (P = 0.023). In conclusion, the higher risk of graft loss after late AR is not fully explained by impaired graft function measured by serum creatinine.

Acute Disease↗
PubMed2004

Association of cytomegalovirus disease and acute rejection with graft loss in kidney transplantation.

BACKGROUND: Cytomegalovirus (CMV) and acute rejection (AR) alone have been associated with an increased risk of graft loss in kidney transplantation. However, little is known about their association with graft loss when both affect the transplant recipient. METHODS: By using the dynamic time-varying covariate approach to the Cox-proportional hazards model, we retrospectively analyzed the strength of association of AR and CMV disease on graft loss in a single-center kidney and simultaneous pancreas-kidney transplant population. RESULTS: Between January 1990 and December 2000, 2,740 kidney and simultaneous pancreas-kidney transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven AR and CMV disease was 45.8% (n=1,254) and 15.3% (n=420), respectively. The risk ratio (RR) for graft loss was increased by the presence of AR (RR=3.7; P<0.0001), CMV disease (RR=1.9; P=0.0007), AR following CMV disease (RR=6.6; P<0.0001), and CMV disease following AR (RR=3.3; P<0.0001). In patients with AR and CMV disease the average time until AR occurred was longer (441 days) when AR followed CMV disease in comparison with when AR preceded CMV disease (47 days). After adjusting for time-dependent risk of AR for kidney graft loss, the order of AR and CMV disease had no association with graft loss (RR=1.2; P=0.5055). CONCLUSIONS: These results demonstrate the strength of AR and CMV disease as prognosticators of impeding kidney graft loss in transplant recipients. Although AR usually precedes CMV disease, the order of AR and CMV disease has no impact on kidney graft loss in kidney and simultaneous pancreas-kidney transplant recipients.

Acute Disease↗
PubMed2004

Campath-1H in renal transplantation: The University of Wisconsin experience.

BACKGROUND: Immune cell depletion is known to prevent renal allograft rejection and injury. We evaluated the humanized monoclonal antibody Campath-1H (alemtuzumab; ILEX Oncology, San Antonio, Texas) in renal transplant recipients for its safety and efficacy in preventing rejection when used in combination with a calcineurin inhibitor, mycophenolate mofetil, and low-dose steroid therapy. METHODS: One hundred twenty-six consecutive renal allograft recipients received 2 doses of Campath-1H antibody on days 0 and 1. Outcomes were compared to patients who received an anti-CD25 antibody (n=799), Thymoglobulin (n=160), or other antibody treatment (n=156) in combination with a calcineurin inhibitor, mycophenolate mofetil, and higher dose steroids. RESULTS: The Campath-1H group overall experienced less rejection than the other 3 groups (P=.037). Patients with delayed graft function experienced less rejection with Campath-1H than control groups (P=.0096) and improved graft survival (P=.0119). There was no difference in infection or malignancies between the 4 groups. CONCLUSIONS: Campath-1H was well tolerated in renal transplant patients and led to significant reductions in incidence of rejection. Patients with delayed graft function experienced significantly improved graft survival.

Adult↗
PubMed2004

Superior long-term results of simultaneous pancreas-kidney transplantation from pediatric donors.

The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation has prompted the use of cadaveric organs from pediatric donors. The long-term outcome and its impact on overall long-term survival are unknown. A total of 680 recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation from pediatric and adult donors between July 1986 and September 2001 were analyzed and compared. Ten-year kidney and pancreas graft survival for SPK transplantation from donors aged <18 years (n = 142) were 80% and 72%, respectively, compared to 61% pancreas and kidney graft survival from donors > or =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post-transplant, blood glucose, HbA1c and creatinine clearance were significantly better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and 65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1 +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002, respectively). Causes of graft failure for kidney and pancreas transplants were similar between the two groups. No statistically significant difference was observed in patient survival between recipients from pediatric donors compared to adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric donors were stratified according to age (3-11 years and 12-17 years) and compared, no difference in kidney or pancreas graft survival was observed (kidney 76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively). Pediatric donors represent a valuable source of organs, providing excellent short- and long-term outcomes. Wide utilization of pediatric organs will substantially increase the donor pool.

Adolescent↗
PubMed2004

Kidney and pancreas transplantation.

Data from the Scientific Registry of Transplant Recipients offer a unique and comprehensive view of US trends in kidney and pancreas waiting list characteristics and outcomes, transplant recipient and donor characteristics, and patient and allograft survival. Important findings from our review of developments during 2002 and the decade's transplantation trends appear below. The kidney waiting list has continued to grow, increasing from 47,830 in 2001 to 50,855 in 2002. This growth has occurred despite the increasing importance of living donor transplantation, which rose from 28% of total kidney transplants in 1993 to 43% in 2002. Policies and procedures to expedite the allocation of expanded criteria donor (ECD) kidneys were developed and implemented during 2002, when 15% of deceased donor transplants were performed with ECD kidneys. Unadjusted 1- and 5-year deceased donor kidney allograft survivals were 81% and 51% for ECD kidney recipients, and 90% and 68% for non-ECD kidney recipients, respectively. Although more patients have been placed on the simultaneous kidney-pancreas waiting list, the number of these transplants dropped from a peak of 970 in 1998 to 905 in 2002. This decline may be due to competition for organs from increasing numbers of isolated pancreas and islet transplants.

Age Distribution↗
PubMed2004

Rituximab as treatment for refractory kidney transplant rejection.

Recent studies have shown that a high density of CD 20+ cells are seen in patients who have steroid-resistant rejection episodes. Rituximab is a high-affinity CD-20 specific antibody that inhibits B-cell proliferation while inducing cellular apoptosis. Thus, it is a rational choice for therapy in transplantation to abrogate B-cell-mediated events. Twenty-seven patients were diagnosed with biopsy-confirmed rejection manifested by thrombotic microangiopathy and/or endothelialitis between 2/99 and 2/02 at our institution. These individuals were treated with a single dose of rituximab, in addition to other therapies, in an effort to reverse their rejection episodes. Twenty-four received additional steroids while 22 of the 27 patients were also treated with plasmapheresis and antithymocyte globulin (ATG). Only three patients experienced graft loss not associated with patient death during the follow-up period (605 +/- 335.3 days). In the 24 successfully treated patients, the serum creatinine at the time of initiating rituximab therapy was 5.6 +/- 1.0 mg/dL and decreased to 0.95 +/- 0.7 mg/dL at discharge. The addition of rituximab may improve outcomes in severe, steroid-resistant or antibody-mediated rejection episodes after kidney transplantation.

Adolescent↗
PubMed2004

Donation after cardiac death: the University of Wisconsin experience.

OBJECTIVES: The objective of this analysis was to compare the results of transplantation of livers, pancreases, kidneys, and lungs from donation after cardiac death (DCD) donors to organs transplanted from donation after brain death (DBD) donors. METHODS: From January 1984 through July 2000, outcomes of 382 DCD kidneys were compared to 1,089 kidneys (SPK) transplants and 36 liver transplants from DCD donors were compared to 455 SPK and 510 liver transplants from DBD donors. Likewise, 31 simultaneous pancreas-kidneys transplants from DBD donors. RESULTS: The rate of delayed graft function (DGF) was higher in kidneys transplanted from DCD donors (27.5% versus 21.3%, p=0.01). Likewise, discharge creatinines were higher in recipients of DCD kidneys (1.9 mg/dL versus 1.7 mg/dL, p=0.001). There was no difference in 10-year graft survival between DCD and DBD recipients (45.0% versus 48.0%, p=0.054). No difference in 5-year pancreatic and renal allograft survival was seen after SPK from DCD or DBD donors. After liver transplantation, biliary strictures were higher in recipients of DCD livers (13.9% versus 8.0%, p=0.03). Likewise, 3-year patient and graft survivals were lower for recipients of DCD livers (65.8% versus 84.9%, p=0.01; and 58.6% versus 76.9%, p=0.006). CONCLUSIONS: This large experience with transplantation from DCD donors demonstrates that similar patient and graft survivals can be expected when compared to recipients of organs from DBD donors.

Brain Death↗
PubMed2003

Chronic allograft nephropathy uniformly affects recipients of cadaveric, nonidentical living-related, and living-unrelated grafts.

BACKGROUND: Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The authors retrospectively compared the development of CAN in recipients of cadaveric (CAD), living-related donor (LRD), and living-unrelated donor (LURD) transplants at their center. METHODS: The authors retrospectively examined the impact of various factors on the incidence of CAN using univariate and multivariate proportional hazards analysis in a single-center kidney transplant population. RESULTS: Between 1 January 1990 and 31 May 2000, 2,140 kidney-alone transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven CAN was 12.2% (n=203). Risk factors for CAN included the number of transplants (P=0.0001), acute rejection (P=0.0001), panel reactive antibody (P=0.0001), discharge creatinine (P=0.0001), 1-year creatinine (P=0.0015), delayed graft function (P=0.007), total human leukocyte antigen (HLA)-B and -DR mismatches (P=0.0005), recipient age (P=0.003), black donor race (P=0.001), black recipient race (0.0457), donor age (P=0.0053), cold storage time (P=0.019), and cytomegalovirus infections (P=0.002). Interestingly, although the LRD HLA-identical recipients had a significantly lower incidence of CAN (P=0.0015), the incidence of CAN in CAD and HLA-nonidentical LRD recipients did not differ. Graft survival was significantly worse in CAD recipients compared with all other groups (P<0.001). CONCLUSIONS: These results demonstrate the importance of immunologic and nonimmunologic factors on the development of CAN. The disparities in overall graft survival, despite the similarities in CAN rates, suggests that other factors, in addition to CAN, influence the increase in graft loss in CAD transplant recipients.

Adult↗
PubMed2003

Underutilization of pancreas donors.

BACKGROUND: Transplantation of the pancreas has become the treatment of choice for selected patients with type 1 diabetes mellitus. With the current shortage of cadaver donors and the increasing number of diabetic patients on the transplant waiting list, there is a critical need to optimally use all available pancreas grafts for transplantation. We have therefore explored the use of traditionally "less-than-ideal" pancreas donors, including pediatric (4-10 years), older (>or=45 years), obese (weight >or=200 lb), and non-heart-beating donors and donors with an elevated amylase (75% greater than normal values). METHODS: A total of 620 primary simultaneous pancreas-kidney transplantations were performed at our center. We analyzed the ratio of livers to pancreata transplanted at our center and compared this to the United Network for Organ Sharing database. Using univariate and multivariate analyses, we then assessed the impact of these less-than-ideal donors on patient survival, graft survival, and postsurgical complications after simultaneous pancreas-kidney transplantation. RESULTS: A substantial nationwide underutilization of pancreata from donor procurements is demonstrated in the United Network for Organ Sharing database. By using these less-than-ideal donors, the ratio of liver to pancreata procured can be reduced to 1.25:1. Graft survival was not significantly different in patients receiving transplants from obese, non-heart-beating, pediatric, or hyperamylasemic donors compared with grafts from ideal donors. However, grafts from donors 45 years of age or older had significantly lower 1- and 5-year graft survival rates (76% and 65% vs. 90% and 80%, P=0.006). CONCLUSIONS: This study demonstrates that utilization of pancreas grafts from selected, less-than-ideal donors results in good overall outcomes and could potentially expand the organ donor pool.

Adolescent↗
PubMed2003

Outcomes in kidney transplantation.

It is estimated that there are greater than 100000 kidney transplant recipients with a functioning graft in the United States. Recent advances in immunosuppression have improved short-term graft survival rates and decreased early mortality by decreasing the incidence and therapy for acute rejection episodes. For those accepted on the waiting list, transplant prolongs patient survival compared with remaining on dialysis. During the 1990s, 3 new immunosuppressive drugs were introduced in clinical kidney transplantation. All were approved for use by the Food and Drug Administration after large, controlled, randomized trials. Mycophenolate mofetil (MMF), when combined with cyclosporine (CSA) and prednisone, lowered acute rejection rates by nearly 50% compared with control. Tacrolimus compared with CSA also significantly reduced acute rejection rates in kidney transplant recipients, but was associated with a significant increase in posttransplant diabetes mellitus (PTDM) in the early trials. When evaluated in combination with MMF, the incidence of PTDM was much lower. At the end of the decade, sirolimus was shown in several randomized trials to lower acute rejection rates and is believed to be less nephrotoxic compared with calcineurin inhibitors. All of the randomized trials were not statistically powered to assess long-term superiority. Registry analyses have been performed that appear to show some long-term benefit of immunosuppressive therapy with MMF. Other outcome assessments in kidney transplant recipients include risk factors for chronic allograft nephropathy, hypertension, hyperlipidemia, and bone disease. Although there are few randomized trials, understanding of the significance of these common complications has progressed and strategies for therapy and intervention have been developed. This article focuses on the randomized trials of immunosuppressive therapy and complications associated with use of these drugs. In addition, we review the current management and intervention for the comorbidities associated with the long-term clinical management of the kidney transplant recipient.

Comorbidity↗
PubMed2003

Determinants of quality of life changes among long-term cardiac transplant survivors: results from longitudinal data.

BACKGROUND: Cross-sectional analyses have identified significant associations between quality of life (QOL), and comorbidities and adverse effects in cardiac transplant recipients. However, little is known about factors that influence changes in QOL over time. This study examines both cross-sectional and longitudinal data from long-term survivors to identify factors that affect differences in QOL among recipients and individual changes in QOL during a 1-year period. METHODS: Self-selected enrollees completed questionnaires, including QOL scales, at 3-month intervals. Repeated measures multiple regression analysis was used to examine the association between the QOL scales and comorbidities, adverse effects, and compliance measures, controlling for other factors. RESULTS: We included 569 participants in the analysis, with a mean time since transplantation of 8.6 years. Cross-sectional results showed that the number of comorbidities, treatment non-compliance, and several adverse effects were associated with low QOL. In longitudinal results, waiting to take medications and taking less medication because of lifestyle restrictions were associated with decreases in QOL over time. Hair loss, changes in face shape, and decreased sexual interest or ability also had the largest adverse effects on changes in QOL. CONCLUSIONS: These findings provide new opportunities for interventions to address factors related to decreases in QOL. Clinicians should actively solicit information about compliance with medication regimens. In addition, information about the adverse effects of medications should be considered when making therapeutic decisions.

Adult↗
PubMed2003

Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study.

Campath-1H, an anti-CD52 monoclonal antibody, was used as induction therapy (40 mg i.v. total dose) in 29 primary human renal transplants, and the patients were maintained on rapamycin monotherapy (levels 8-15 ng/mL) post-transplant. Campath-1H profoundly depletes lymphocytes long-term and more transiently depletes B cells and monocytes. All patients are alive and well at 3-29 months of follow up. One graft was lost because of rejection. There have been no systemic infections and no malignancies. Eight of 29 patients have experienced rejection, which was successfully treated in seven of eight patients. Five of these patients had pathological evidence of a humoral component of their rejection. Seven of the 29 patients were converted to standard triple therapy on account of rejection. Rapamycin was generally well tolerated in that there were no significant wound-healing problems; two lymphoceles required surgical drainage; and most patients were treated with a lipid-lowering agent. Flow crossmatch testing post-transplant revealed evidence of alloantibody in two patients tested with previous combined cellular and humoral rejection. Biopsies have shown no chronic allograft nephropathy to date. In view of the relatively high incidence of early humoral rejection, we plan to modify the immunosuppressive regimen in subsequent pilot studies. This clinical trial provides insight into the use of Campath-1H induction in combination with rapamycin maintenance monotherapy.

Adolescent↗
PubMed2003

Surgical repair of transplant renal artery stenosis with preserved cadaveric iliac artery grafts.

OBJECTIVE: To review the authors' experience with ABO-matched, preserved, cadaveric, iliac artery grafts for treatment of transplant renal artery stenosis (TRAS). SUMMARY BACKGROUND DATA: TRAS is an important and treatable cause of hypertension and graft dysfunction in renal allograft recipients. Surgical treatment is reserved for lesions that are not amenable to percutaneous transluminal angioplasty (PTA) or for recurrence after PTA. Various surgical options for reconstruction of the transplant renal artery exist, although no single technique has been demonstrated to be superior. The authors have used preserved, blood type-matched, iliac artery grafts procured from cadaver organ donors to reconstruct transplant renal arteries in patients with specific lesions and following unsuccessful PTAs. METHODS: Between 1991 and 2001, 21 patients underwent reconstruction of allograft renal arteries using cadaveric iliac artery as conduit. Charts, operative notes, and imaging studies of all patients were reviewed. A successful intervention for TRAS was defined as technical success as well as a decrease in serum creatinine and/or blood pressure 6 weeks after the procedure. Development of a hemodynamically significant lesion following renal artery reconstruction was considered a recurrence. RESULTS: In patients treated with surgical reconstruction, hemodynamically significant TRAS occurred at or within 1 to 2 mm of the anastomosis in 13 patients, in the middle of the renal artery in 4, and secondary to a kink in 2 patients. Surgical treatment was undertaken in seven patients following unsuccessful PTA. Two patients had aneurysms of the iliac artery. Reconstruction using cadaveric iliac artery was successful in 19 of 21 (90%) patients, and only 1 these patients (4.8%) failed due to recurrence, with a median follow-up of 42 months. Graft loss secondary to TRAS occurred in two patients. The authors have not seen any long-term complications related to cadaveric iliac artery grafts, and the majority of the allografts continue to function well. CONCLUSIONS: Surgical reconstruction of the transplant renal artery with blood type-matched iliac artery grafts should be considered a viable option for patients with specific anatomic lesions, those who have had an unsuccessful PTA, and those with recurrence following PTA.

Adult↗
PubMed2003

Long-term outcomes in simultaneous pancreas-kidney transplantation: lessons relearned.

We analyzed 752 simultaneous pancreas kidney transplants performed at the University of Wisconsin from December 1985-February 2003. Patient survival rates at 5 and 10 years were 88% and 77%. The 5- and 10-year pancreas survival rates were 78% and 61% and the corresponding kidney survival rates were 80% and 59%. In this limited retrospective analysis of outcomes after simultaneous pancreas-kidney transplantation, the importance of donor selection is re-emphasized. Donor age and donor BMI significantly impact on graft and recipient survival. Furthermore, complications following SPK transplantation negatively impact on outcomes.

Adolescent↗
PubMed2002

Life satisfaction and adverse effects in renal transplant recipients: a longitudinal analysis.

INTRODUCTION: Previous cross-sectional analyses have identified significant associations between quality of life (QOL), comorbidities and adverse effects in renal transplant recipients. This report examines the longitudinal relationship between adverse effects and QOL, with particular attention to the relative impact of adverse effects associated with immunosuppression. METHODS: The Transplant Learning Center (TLC) is a program designed to improve QOL and preserve graft function in transplant recipients. Self-selected enrollees filled out questionnaires at roughly 3-month intervals. Each questionnaire included QOL scales developed for the program. Repeated measures multiple regression analysis was used to examine the relationship between the QOL scales, comorbidities, adverse effects, adjusting for other factors. RESULTS: A total of 4247 TLC enrollees were included in the analysis, with a mean time since transplant of 5.1 yr. Comorbidities and adverse effects were common, with high blood pressure reported by 87% of respondents and unusual hair growth reported by 69.6%. In bivariate analysis, emotional/psychological problems and headaches had the largest impact on QOL. In multivariate analysis, emotional/psychological problems decreased sexual interest or ability, and headache had the largest adverse QOL effect. CONCLUSIONS: We have identified QOL issues that have been previously underemphasized in transplant recipients. These findings open new areas of research to further explore and define these issues. They provide new opportunities for interventions to address factors adversely impacting QOL and to develop strategies to improve QOL in these patients. Clinicians should actively solicit information about adverse effects of medications, particularly information about sexual and relationship issues, when evaluating renal recipients. These issues should be taken into account when making therapeutic decisions.

Comorbidity↗