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Hans W Sollinger

Publications and source records attributed to Hans W Sollinger.

At least 19 recordsLinked to original sources
PubMed2006

The emerging role of rituximab in organ transplantation.

Long-term acceptance of solid organ allografts remains a challenge. While many acute rejection episodes can be treated, new mechanisms of allograft damage are now being defined especially in kidney transplantation. Unexpected clusters of CD20(+) cells have been discovered in renal biopsies performed for clinical rejection. C4d deposition is now routinely seen in refractory rejection. Despite the rapid introduction of new immunosuppressive agents in transplantation, the search for an efficacious anti-B-cell agent remains. With novel mechanisms of allograft damage now being defined, it is important to consider how an anti-B-cell agent might fit into an immunosuppressive regimen. Rituximab is a high-affinity CD20 specific antibody that depletes the B-cell compartment by inducing cellular apoptosis. Thus, it is a rational choice for therapy in transplantation to abrogate B-cell mediated events. In this review, we will discuss the mechanisms of action of rituximab, and its use in for a variety of indications in solid organ transplantation. There are emerging case reports that show that rituximab may be an effective agent to treat antibody-mediated rejection, and post-transplant lymphoproliferative disorder. Rituximab has been frequently cited as an important adjunct therapy in desensitization protocols for highly sensitized transplant recipients as well as recipients of ABO incompatible transplants. Rituximab demonstrates promise in this regard and warrants additional consideration in prospective clinical trials.

Animals↗
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

Validation of large particle flow cytometry for the analysis and sorting of intact pancreatic islets.

BACKGROUND: Accurate quantification of total islet yield is an essential step prior to transplantation and for research. The standard method of manually determining an islet equivalent (IEQ) count is subjective and prone to error. We evaluated Complex Object Parametric Analyzer and Sorter (COPAS) large particle flow cytometry for the determination of islet equivalent counts and purities of islet preparations. METHODS: Initial validation of the sensitivity and accuracy of the COPAS flow cytometer was performed by analysis and sorting of uniform polystyrene microspheres with sizes similar to islets. Human and Rhesus monkey islets were stained with the zinc-specific fluorescent dye Newport Green to discriminate islet from nonislet tissue. Islet sizes were extrapolated from standard curves obtained using microspheres from which individual islet volumes were calculated. IEQ counts on six islet preparations were performed by the standard manual method and compared with results obtained by automated COPAS flow cytometry. RESULTS: The COPAS flow cytometer was highly accurate in the detection and measurement of both polystyrene microspheres and islets. IEQ counts determined by COPAS flow cytometry were consistent with manual counts although subject to error when assessing preparations with significant numbers of islets embedded within acinar tissue. Size-specific islet sorting with retention of morphology and dithizone staining was also shown using the COPAS flow cytometer. CONCLUSIONS: COPAS large particle flow cytometry provides a novel automated approach for quantification of intact islets and determination of islet equivalent yield. In addition, the ability to analyze and sort islets based upon user defined criterion opens unique avenues for experimentation.

Animals↗
PubMed2005

Liver transplantation for HELLP syndrome.

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a rare complication of pregnancy that is associated with preeclampsia and may result in rupture of the liver. Although there have been case reports of liver transplantation for HELLP syndrome, the outcomes of transplantation for this rare indication have not been reported. Furthermore, the optimal management of complicated HELLP syndrome and indications for liver transplantation are unclear. Our objective was to review the national experience with liver transplantation for HELLP syndrome and to develop a comprehensive algorithm for the management of liver complications of HELLP syndrome, including indications for transplantation. A recent case from our institution is reported and the literature is reviewed. The results of liver transplantation for HELLP syndrome were analyzed from the United Network for Organ Sharing database. Between October 1987 and November 2003 there have been 8 deceased donor liver transplants performed for complications related to HELLP syndrome. As of the most recent follow-up, 6 of the 8 patients are alive, with both deaths occurring within 1 month of transplantation, and 2 patients have required retransplantation. This review supports that good results can be obtained with liver transplantation for patients with complicated HELLP syndrome that have either ongoing, uncontrolled hemorrhage or liver necrosis and failure. Patients with complicated HELLP syndrome are best managed at a center with expertise in liver transplantation.

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

Donation after cardiac death: the University of Wisconsin experience with liver transplantation.

OBJECTIVE: To determine whether the outcomes of liver transplantation (LTx) from donation after cardiac death (DCD) donors are equivalent to those from donation after brain death (DBD) donors. SUMMARY BACKGROUND DATA: Because of the significant donor organ shortage, more transplant centers are using livers recovered from DCD donors. However, long-term, single-center outcomes of liver transplantation from DCD donors are limited. METHODS: From January 1, 1993, to July 31, 2002, 553 liver transplants were performed from DBD donors and 36 were performed from DCD donors. Differences in event rates between the groups were compared with Kaplan-Meier estimates and the log-rank test. Differences in proportion and differences of means between the groups were compared with Fisher exact test and the Wilcoxon rank sum test, respectively. RESULTS: Mean warm ischemic time at recovery in the DCD group was 17.8 +/- 10.6 minutes. The overall rate of biliary strictures was greater in the DCD group at 1 year (33% versus 10%) and 3 years (37% versus 12%; P = 0.0001). The incidence of hepatic artery thrombosis, portal vein stenosis/thrombosis, ischemic-type biliary stricture (ITBS), and primary nonfunction were similar between groups. However, the incidence of both hepatic artery stenosis (16.6% versus 5.4%; P = 0.001) and hepatic abscess and biloma formation (16.7% versus 8.3%; P = 0.04) were greater in the DCD group. Trends toward worse patient and graft survival and increased incidence of ITBS were seen in DCD donors greater than 40 years compared with DCD donors less than 40 years. Overall patient survival at 1 year (DCD, 80%; versus DBD, 91%) and 3 years (DCD, 68%; versus DBD, 84%) was significantly less in the DCD group (P = 0.002). Similarly, graft survival at 1 year (DCD, 67%; versus DBD, 86%) and 3 years (DCD, 56%; versus DBD, 80%) were significantly less in the DCD group (P = 0.0001). CONCLUSIONS: Despite similar rates of primary nonfunction, LTx after controlled DCD resulted in worse patient and graft survival compared with LTx after DBD and increased incidence of biliary complications and hepatic artery stenosis. However, overall results of LTx after controlled DCD are encouraging; and with careful donor and recipient selection, LTx after DCD may successfully increase the donor liver pool.

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↗
PubMed2005

Prevention of chronic allograft nephropathy with vitamin D.

Chronic allograft nephropathy (CAN) is the leading cause of late allograft loss in kidney transplantation. Interstitial fibrosis and glomerulosclerosis are characteristic of CAN. Transforming growth factor beta-1 (TGFbeta-1) is associated with both of these histologic findings in the transplant setting. Recent studies have suggested that vitamin D signaling pathways may interact with and regulate TGFbeta-1 mediated events. We examined the efficacy of 1,25-dihydroxyvitamin D(3), the active metabolite of vitamin D [1,25-(OH)(2)D(3)], the active metabolite of vitamin D, as monotherapy to prolong allograft survival and preserve renal function in a rat model of CAN, the Fisher 344 to Lewis model. Recipients went without treatment or were treated with cyclosporine A (CSA; 10 days) or 1,25(OH)(2)D(3) (1000, 500 or 250 ng/kg/day). Grafts were harvested at the time of rejection or at 24 weeks post-transplant. A portion of the graft was processed for histology and immunohistochemistry and a second portion was analyzed for protein expression by western blotting. Not only did 1,25-(OH)(2)D(3) treatment significantly prolong graft survival, but it also prevented histological changes associated with CAN. 1,25-(OH)(2)D(3) treatment significantly decreased Smad 2 expression. This TGFbeta signaling molecule is likely involved in fibrosis. Moreover, 1,25-(OH)(2)D(3) treatment increased Smad 7 expression, an important feedback molecule in the TGFbeta-1 signaling pathway. This suggests that 1,25-(OH)(2)D(3) interacts with TGFbeta-1 in limiting histological injury in this model of CAN. Furthermore, 1,25-(OH)(2)D(3), treatment increased expression of matrix metalloproteinase 2 (MMP-2), thus directly affecting levels of another important matrix molecule. Taken together our data suggests that 1,25-(OH)(2)D(3) mitigates CAN in this model by altering TGFbeta-1 and matrix-regulating molecules.

Animals↗
PubMed2005

Campath-1H use in pediatric renal transplantation.

Campath-1H is a humanized, monoclonal antibody directed against CD52 determinants on the surface of human B- and T-cells and monocytes. Reports of Campath-1H use as induction in adult renal transplantation have been encouraging with low rejection rates and minimal adverse events. We report four high risk pediatric kidney transplant patients who received Campath-1H for unique indications with variable results. Children ranged in age from 20 months to 16 years. Immunosuppression regimens varied. Three of four patients experienced acute rejection, two of which were C4d positive. Serial flow cytometry was performed on all four patients. The patient who received only Campath-1H has an absolute lymphocyte count that remains less than 50% of baseline at 12-months post-transplant. In addition, in this patient CD3, CD4, CD8 and CD20 remain less than 50% of baseline. From this initial experience using Campath-1H in pediatric renal transplantation we conclude that; (1) the use of Campath-1H does not prevent recurrence of FSGS, (2) as seen in adults, lack of calcineurin inhibition when using Campath-1H may increase the risk of antibody-mediated rejection and (3) prolonged lymphocyte depletion remains even after a single dose of Campath-1H in children.

Adolescent↗
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

Correlation between human leukocyte antigen antibody production and serum creatinine in patients receiving sirolimus monotherapy after Campath-1H induction.

BACKGROUND: In this study, we determined whether Campath-1H induction followed by sirolimus monotherapy inhibited alloantibody production in renal transplantation. Second, we evaluated the correlation between human leukocyte antigen (HLA) antibody production and serum creatinine levels. METHODS: Sera were taken 1 to 24 months after transplantation from 24 patients treated with Campath-1H and sirolimus and tested for serum creatinine and HLA-specific antibody by using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: Ten (42%) of the 24 patients treated with Campath-1H and sirolimus produced HLA antibodies. Six of these 10 developed both donor-specific antibodies (DSAs) and non-donor-specific antibodies (NDSAs), whereas only NDSAs were detected in the other four patients. In patients with biopsy-diagnosed humoral rejection (C4d+), serum levels of both DSA and NDSA significantly correlated with patient serum creatinine levels. Rejection treatment successfully reduced both DSAs and NDSAs and reversed humoral rejection. CONCLUSIONS: The numeric relationship between serum creatinine and DSA levels suggests a causal relationship between alloantibody and transplant rejection.

Alemtuzumab↗
PubMed2004

Advances in pancreas transplantation.

Despite early obstacles impacting the success of pancreatic transplantation, the introduction of new procedures and new immunosuppressive therapies during the past 2 decades has improved outcomes for pancreatic transplant recipients. For example, the use of bladder drainage and better human leukocyte antigen matching has helped overcome some of the early obstacles of pancreatic transplantation. In addition, the introduction of tacrolimus in 1994 and mycophenolate mofetil in 1996 has helped lower rates of acute rejection and increase graft survival, with less nephrotoxicity than treatment with cyclosporine. Regimens allowing the tapering of corticosteroids have also helped reduce the rates of acute pancreas rejection. To further improve therapeutic options for patients with type 1 diabetes or end-stage renal disease, pancreatic islet transplantation and organ and islet xenotransplantation should be further explored.

Diabetes Mellitus, Type 1↗
PubMed2004

Modified technique of ureteroureterostomy in rat kidney transplantation.

Different strain combinations of rats are available to study immunological and transplant-related problems in the models of kidney transplantation. Although numerous modifications of surgical techniques for ureteric reconstruction are evaluated in order to reduce complications and to extend long-term survival, ureteric complications still occur frequently, especially when the difference in diameter of both donor and host ureters is disproportionate. Instead of using the current nonsplinted ureteroureterostomy (method A), a versatile and rapid technical modification (method B) was developed to perform reconstruction of ureters with disproportionate diameters. The overall incidence of ureteric complications was 80% (8/10) using method A, whereas this rate was significantly reduced to 15% (3/20) using method B (P < 0.001). Our modification proves the feasibility of nonsplinted ureteroureterostomy in a technical, highly demanding rat model of kidney transplantation with an acceptable rate of ureteric complication, considering the disproportionate difference in diameter between the host and donor ureters.

Anastomosis, Surgical↗
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

Mycophenolates in transplantation.

The discovery of mycophenolic acid (MPA) as a potent immunosuppressant, able to inhibit B- and T-cell proliferation by blocking production of guanosine nucleotides required for DNA synthesis, allowed its potential in the field of transplantation to be realized. Mycophenolate mofetil (MMF), an MPA prodrug, has been shown to be an effective immunosuppressant in transplant therapy. Clinical trials in renal, heart, and liver transplant recipients have demonstrated that, in combination with cyclosporine and steroids, MMF therapy can reduce the incidence and severity of acute rejection episodes and improve graft and patient survival as well as graft function. Although MMF is generally well tolerated, optimal therapy may be limited by associated side effects, in particular gastrointestinal (GI) toxicity, which may occur in over 40% of patients. Dose changes resulting from GI side effects may potentially lead to sub-therapeutic dosing and impaired clinical outcomes. An enteric-coated formulation delivering MPA - enteric-coated mycophenolate sodium (EC-MPS) has been developed to improve MPA-related upper GI adverse events. EC-MPS delays the release of MPA, consistent with a functional enteric-coating. Recent clinical trials have demonstrated that EC-MPS is as effective and safe as MMF in both de novo and maintenance renal transplant patients.

Gastrointestinal Tract↗
PubMed2004

Immune regulation and graft survival in kidney transplant recipients are both enhanced by human leukocyte antigen matching.

We hypothesized that donor/recipient sharing of the human leukocyte antigen (HLA) involved in allopeptide presentation to the T regulatory cell increases the incidence of immune regulation, thus contributing to long-term graft survival. Peripheral blood mononuclear cells (PBMC) were obtained from 40 living related donor (LRD) and 31 cadaver renal transplant recipients. The trans vivo delayed type hypersensitivity (DTH) assay was used to assign patients to regulator, nonregulator, and sensitized categories. In a large cohort (n=1934 patients), primary graft survival and rejection episodes were analyzed using a log rank test for comparison with the DTH results. The highest incidence of regulated anti-donor DTH was observed in the LRD HLA-identical group (6/6; 100%) followed by the LRD HLA 1 haplotype matched group (18/27; 67%). Within the cadaver population, two DR-matched recipients had a higher frequency of regulated anti-donor DTH (6/11; 55%) than 1 & 0 DR-matched recipients (3/18; 17%). In a multivariate model, matching for HLA-DR alone, or for DR plus DQ was significantly (p=0.045, p=0.041) correlated with DTH regulation. The better HLA-matched groups showed the highest incidence of DTH regulation and, in a larger retrospective analysis, displayed better graft survival and freedom from acute rejection (p<0.0001). HLA matching, and HLA-DR matching in particular, correlates with the incidence of immune regulation after kidney transplantation.

Adult↗