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Bryan N Becker

Publications and source records attributed to Bryan N Becker.

At least 37 records · Page 2Linked to original sources
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

The type 1 angiotensin II receptor tail affects receptor targeting, internalization, and membrane fusion properties.

Endocytosis modulates cell responses by removing and recycling receptors from the cell surface. Type I angiotensin II receptors (AT1R) are somewhat unique in that they are expressed at apical (AP) and basolateral (BL) membranes in proximal tubule cells and both receptor sites undergo endocytosis. We analyzed AT1R cytoplasmic (-COOH) tail deletion mutants to determine whether classic AT1R endocytosis motifs functioned similarly in polarized cells and simultaneously altered receptor properties. Serially truncating the AT1R tail had little effect on AP/BL AT1R distribution as determined by 125I-angiotensin II binding in LLCPK(Cl4) cells transfected with an AT1R transcript. AP AT1R expression required the proximal 12 amino acids in the AT1R-COOH tail. Deleting all but the proximal 12 aa of the AT1R-COOH tail (T316L mutant) decreased AP AT1R internalization at 20 min (17 +/- 6%; p < 0.05 versus full-length; n = 5) and inhibited AP AT1R-stimulated arachidonic acid release (counts released per milligram of protein at 20 min: full-length, 18,762 +/- 4018; T316L, 2430 +/- 1711; n = 4; p < 0.02). Endosomal fusion assays were performed using peptide sequences of regions in the AT1R tail involved in endocytosis (YFLQLLKYIPP [LL] and LSTKMSTLSY [STL]). Peptide STL significantly inhibited endosomal fusion (22 +/- 10% of control; n = 5; p < 0.05 versus positive control). Peptide LL had no significant inhibitory effect. AT(1)R in polarized cells contain dominant endocytosis signals but these motifs do not correlate with AP or BL AT1R expression. Moreover, peptide sequences within the AT1R-COOH tail necessary for endocytosis also modulate endosomal fusion properties.

Amino Acid Sequence↗
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

Increasing hematocrit reduces early posttransplant cardiovascular risk in diabetic transplant recipients.

BACKGROUND: Cardiovascular disease remains epidemic in transplant recipients, despite aggressive treatment of cardiovascular risk factors. Thus, novel risk factors could play a role in the genesis of cardiovascular events in this population. METHODS: We evaluated the impact of early posttransplant anemia on cardiovascular events. We examined rolling average hematocrit values at 30-day intervals and determined the effect of increasing hematocrit on the risk for cardiovascular (CV) events in a single-center population of 404 type 1 diabetic end-stage renal disease patients who underwent either cadaveric kidney transplantation alone or simultaneous pancreas-kidney transplantation. RESULTS: Greater than 60% of the individuals in the study cohort had hematocrit less than or equal to 30% at least once during the first 30 days posttransplant. Forty-two individuals (10.4% of the study population) had at least one 30-day rolling hematocrit less than or equal to 30% and a CV event (myocardial infarction, CV death, angina, congestive heart failure) during the first 26 weeks of the posttransplant course. Increasing hematocrit (>30%) led to a reduction in the risk ratio (RR) for a CV event compared with hematocrit less than or equal to 30% (RR, 0.237; P=0.015). The association between anemia and CV events remained statistically significant in a multivariate analysis (RR, 0.65; P=0.022) that also included age and a history of pretransplant ischemic heart disease. CONCLUSIONS: These data suggest that anemia is an important risk factor for early posttransplant CV events in a high-risk population. Prospective studies of anemia management therapy in this setting are warranted to determine whether this will reduce early posttransplant CV risk.

Adult↗
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

L-carnitine treatment of anemia.

Recombinant human erythropoietin (rHuEPO) and iron supplementation have had a profoundly positive impact on the anemia of patients with chronic kidney disease. However, a significant number of patients remain hyporesponsive to rHuEPO, with hemoglobin values less than target levels. A suboptimal response to rHuEPO is associated with complications that can reduce quality of life and increase morbidity, mortality, and costs. There are a number of other metabolic derangements associated with uremia that can impact on the production and survival of red blood cells. Dialysis-related carnitine disorder is a functional metabolic deficiency, common in chronic dialysis patients, that can have a negative impact on erythrocyte production and survival. This article reviews the role of L-carnitine in the pathogenesis and adjunctive treatment of anemia associated with kidney failure. After a comprehensive database search, primary and secondary reports were analyzed. Laboratory studies examining the influence of carnitine on red blood cell function and clinical trials of L-carnitine in dialysis patients support the use of L-carnitine in the setting of rHuEPO hyporesponsiveness. Consensus groups, including the National Kidney Foundation-Kidney Disease Outcome Quality Initiative (K/DOQI), consider the use of L-carnitine for hyporesponsive rHuEPO-dependent anemia a promising application of this therapy, recommending an empiric trial of L-carnitine in these patients.

Anemia↗
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

Disease progression and outcomes in chronic kidney disease and renal transplantation.

BACKGROUND: It is unknown whether renal transplant recipients (RTR) have better outcomes and disease progression rates compared to patients with chronic kidney disease (CKD) when matched for the level of kidney function. METHODS: We analyzed data on 1762 patients with CKD (N = 872) and RTR (N = 890) over 16 years, applying the new Kidney/Disease Outcomes Quality Initiative (K/DOQI) staging system for CKD in a single center retrospective study. Patients were further divided based their native kidney disease. We determined disease progression by the slope of creatinine clearance decline and patient and kidney survival rates adjusted for age, gender and stage of kidney function, using Cox proportional hazards models. RESULTS: The overall rate of creatinine clearance decline in patients with CKD was -6.6 +/- 8.7 mL/min/year compared to -1.9 +/- 4.7 mL/min/year in RTR (P < 0.0001). The rate of decline per stage of CKD was also significantly lower in RTR. Whereas overall kidney survival was higher in RTR compared to patients with CKD (49.6% vs. 17.2%, respectively, P < 0.001), patient survival was not statistically different between the two groups (74.7% vs. 80.3%, respectively, P = 0.25). CONCLUSION: RTR had similar mortality rates compared to patients with CKD despite enjoying slower rates of disease progression and better kidney survival rates. These data suggest that RTR are a unique subset of patients with CKD whose comorbid conditions likely offset the potential benefits of slower rates of progression.

Adult↗
PubMed2002

Vitamin D as immunomodulatory therapy for kidney transplantation.

Vitamin D (1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)]) has been studied in the past for its immunosuppressive properties, and, in that context, it may also have potential utility as an immunomodulatory agent for transplantation. A number of studies have demonstrated that 1alpha,25-(OH)(2)D(3) or its analogs regulate immune cell proliferation, differentiation, and responsiveness. A burgeoning number of studies have also explored using 1alpha,25-(OH)(2)D(3) and its analogs directly as therapy in animal models of kidney transplantation with success in prolonging allograft function and preventing acute rejection. Some of these in vivo effects may well be caused by alterations in immune cell function, but it is also possible that exogenous 1alpha,25-(OH)(2)D(3) and its analogs are altering the intragraft milieu as well, specifically through changes in the TGF-beta signaling cascade. Such provocative data and the availability of newer 1alpha,25-(OH)(2)D(3) analogs that may limit side effects (e.g. hypercalcemia) have created interest in examining this secosteroid clinically in kidney transplantation.

Adjuvants, Immunologic↗
PubMed2002

Diabetic kidneys can safely expand the donor pool.

BACKGROUND: The demand for organs has increased exponentially with a new name added to the United States waiting list every 16 min. As such, kidneys from medically marginal donors are being considered for transplantation more frequently, including kidneys from individuals already at risk for renal disease, e.g., diabetic donors. METHODS: We compared outcomes when using kidneys from donors with type 1 diabetes mellitus (D1) or type 2 diabetes mellitus (D2) at our center as a function of time. All patients with available data who underwent renal transplantation were evaluated (n=2013). RESULTS: Forty-two individuals were recipients of D1 or D2 donor kidneys. Thirty of these individuals did not have diabetes (R0). All patients received quadruple sequential immunosuppression with cyclosporine (CsA) or tacrolimus (FK506). Donor serum creatinine (Scr) values were not significantly different. D2 kidneys came from older donors (mean age, 56+/-10.4 years; P< or =0.01 vs. D1 and D0 donors). Mean discharge Scr was greater in nondiabetic D2 recipients (D2/R0, 2.45+/-1.3 mg/dl; P=0.0016 vs. D0/R0), and transplantation of D1 or D2 kidneys was associated with a significantly increased frequency of posttransplant proteinuria (P=0.0089). Interestingly, R0 recipients of D1 or D2 kidneys were more likely to initiate oral hypoglycemic therapy after transplant (P=0.04). However, rejection episodes were not significantly different among groups, and long-term graft survival and patient survival were similar among groups. CONCLUSIONS: These data suggest that diabetic kidneys can be safely used without risk to patient or graft survival. Preexisting diabetic injury in the donor may increase the risk for proteinuria, compromised renal function, and posttransplant glucose intolerance.

Adult↗
PubMed2002

Reassessing the impact of cytomegalovirus infection in kidney and kidney-pancreas transplantation.

New antiviral agents and practice guidelines have been implemented to address cytomegalovirus (CMV) infection in organ transplantation. We hypothesized that such measures would reduce rates of symptomatic CMV infection, CMV disease, and CMV seroconversion and associated complications in renal transplant and simultaneous pancreas-kidney transplant recipients. We analyzed the impact of CMV in 1,424 renal transplant and simultaneous pancreas-kidney transplant recipients, transplanted at our center between January 1, 1994 and June 30, 1999. Most patients received quadruple sequential immunosuppression with high-dose acyclovir (800 mg four times daily) for 12 weeks as prophylaxis. High-risk patients (donor CMV-positive/recipient CMV-negative) received ganciclovir (500 to 1,000 mg three times daily) beginning in 1998, again for 12 weeks. One hundred and one renal transplant (9.0%) and 40 simultaneous pancreas-kidney transplant (13.4%) recipients experienced symptomatic CMV infection or CMV disease. Donor CMV-positive/recipient CMV-negative patients had the greatest rates of CMV infection or CMV disease (25.2%; P = 0.0001 versus all other categories). The impact of CMV on outcomes was evaluated in a proportional hazards model. Symptomatic CMV infection or CMV disease increased the risk for subsequent rejection (relative risk, 2.11; P = 0.003) and non-CMV infection (relative risk, 2.24; P = 0.001). To determine if the effects of ganciclovir were masked by pre-1998 data, CMV infection and CMV disease rates for ganciclovir-treated patients (n = 62) were censored at 1 year and compared with acyclovir-treated patients (n = 287). Ganciclovir was associated with trends toward lower rates of infection and disease. It also delayed the time to infection or disease. Serologic testing in high-risk patients also showed late seroconversion, with 20% of patients seroconverting by 6 months, 12 weeks after the prophylaxis period. These data suggest that despite better prophylaxis strategies, CMV remains an important pathogen in renal transplant and simultaneous pancreas-kidney transplant recipients. This finding may require reassessment of prophylaxis strategies and the development of alternative or novel anti-CMV regimens.

Acyclovir↗
PubMed2002

A novel method for regional citrate anticoagulation in continuous venovenous hemofiltration (CVVHF).

BACKGROUND: Continuous renal replacement therapy (CRRT) is increasingly used in managing acute renal failure (ARF) as it offers hemodynamic stability and significant solute clearance in this setting. However, it also requires anticoagulation. Traditionally, heparin has been the anticoagulant of choice but this increases hemorrhagic risk in already high-risk ARF patients. Regional citrate anticoagulation offsets this risk. However, it can be difficult to manipulate regional anticoagulation in CRRT. Moreover, citrate CRRT has been plagued by short optimal filter patency times. METHODS: We designed a novel citrate-based anticoagulation schema for continuous venovenous hemofiltration (CVVHF). We implemented this schema prospectively in caring for 24 individuals admitted to the intensive care unit with ARF requiring CRRT. Each individual had a contraindication to systemic anticoagulation. We evaluated filter patency using Kaplan-Meier methodology, comparing the effect of this citrate-CVVHF system to historical, saline-flush control CVVHF systems. RESULTS: 58 filters ran for a total of 2637.5 h. Average filter patency time was 45.4 +/- 25.5 h. At 48 h, 70% of the CVVHF-citrate system filters remained patent compared to only 16% of historical control saline-flush systems (p = 0.0001). The average filtered urea nitrogen/blood urea nitrogen ratio was 0.84 +/- 0.06 with an average urea clearance of 28.5 +/- 4.1 mL/min for CVVHF-citrate-treated individuals. Only three patients experienced transient complications related to CVVHF-citrate with resolution of these complications within 24 h. Ultimately, 58.3% of the CVVHF-citrate-treated patients survived to ICU discharge. CONCLUSIONS: This novel CVVHF-citrate system achieved excellent clearance and dramatically improved filter patency compared to saline-flush systems. Moreover, it did so with minimal toxicity.

Acute Kidney Injury↗
PubMed2002

Erythropoietin therapy may retard progression in chronic renal transplant dysfunction.

BACKGROUND: Recent data suggests that erythropoietin therapy may actually retard the progression of chronic kidney disease (CKD). Transplant recipients with evidence of chronic allograft dysfunction could respond in a similar manner to erythropoietin. METHODS: We evaluated 166 individuals who initiated erythropoietin therapy after at least 18 days of transplant function. One hundred and nine individuals received erythropoietin between days 18 and 294 of transplant function (group 1-early epoietin alfa) while 57 individuals received erythropoietin on or after day 294 of transplant function (group 2-late epoietin alfa). The slope of serum creatinine (Scr) (Deltaslope Scr) prior to and following the start of erythropoietin therapy and calculated glomerular filtration rates (GFR) were used to assess renal function over time. RESULTS: The average haematocrit rose 6.6% in group 1 patients and 2.1% in group 2 patients during the first 100 days of erythropoietin therapy. The Deltaslope Scr was not significantly altered in group 1 patients. However, for group 2 individuals who continued to have graft function (n=35), the Deltaslope Scr became negative during erythropoietin treatment. This indicated a deceleration in the rate of loss of renal function (day 200 Deltaslope Scr -0.0033, P=0.00091; day 300 Deltaslope Scr -0.0014, P=0.05; day 400 Deltaslope Scr -0.0066, N.S., P=0.066). GFR remained stable in both cohorts. Finally, group 2-late epoietin alfa patients treated with erythropoietin demonstrated a marked trend towards longer graft survival than a group of similar control patients (N.S., P=0.064). CONCLUSIONS: The data in a group of renal transplant recipients with chronic allograft dysfunction reinforce data from the CKD realm suggesting that erythropoietin may be of benefit in slowing the rate of loss of function over time. However, this renal response is not evident in all patients. Prospective studies of erythropoietin or erythropoietin-like medications are warranted in this population to better discriminate those who may respond well to administration of these drugs.

Adult↗
PubMed2002

Long-term follow-up of patients with tertiary hyperparathyroidism treated by resection of a single or double adenoma.

OBJECTIVE: To determine whether patients with tertiary hyperparathyroidism due to single- or two-gland disease undergoing limited resection have similar long-term outcomes compared with patients with hyperplasia undergoing subtotal or total parathyroidectomy. SUMMARY BACKGROUND DATA: Tertiary hyperparathyroidism occurs in less than 2% of patients after renal transplantation. Approximately 30% of these cases are caused by one or two hyperfunctioning glands. Nevertheless, the standard operation for this disease has been subtotal or total parathyroidectomy with autotransplantation. METHODS: Seventy-one patients underwent surgery for tertiary hyperparathyroidism. At the time of surgery, 19 patients who had a single or double adenoma underwent limited resection of the enlarged glands only (adenoma group). The remaining 52 patients with three- or four-gland hyperplasia had subtotal or total parathyroidectomy with implantation (hyper group). Long-term cure rates between the two groups were compared. RESULTS: In the adenoma group, 7 patients had a single adenoma and 12 underwent resection of a double adenoma. In the hyper group, 49 patients had subtotal and 3 had total parathyroidectomies. After surgery, 70 of 71 patients (99%) were cured of their hypercalcemia. The incidence of postoperative transient hypocalcemia was significantly higher in the hyper group (27% vs. 5%). No patients in either group had permanent hypocalcemia requiring long-term supplementation. With up to 16 years of follow-up, there have been no recurrences in the adenoma group, whereas three patients (6%) in the hyper group have had recurrent or persistent hyperparathyroidism. CONCLUSIONS: Patients with tertiary hyperparathyroidism who underwent limited resection of a single or double adenoma only had equivalent long-term cure rates compared with patients undergoing more extensive resections. Therefore, the authors recommend in patients with tertiary hyperparathyroidism and enlargement of only one or two parathyroid glands that the resection be limited to these abnormal glands only.

Adenoma↗
PubMedDate not supplied

Life after transplantation: new transitions in quality of life and psychological distress.

Individuals with kidney failure often elect to undergo kidney transplantation because they believe that they will be more active and return a sense of normality to their lives with a functioning transplant. Therefore it is important to assess whether these objectives are being met. To do so, we can examine health-related quality of life (HRQOL) in transplant recipients. A number of tools have been used for this purpose, including general HRQOL instruments such as the 36-item short-form health survey (SF-36) and transplant-specific surveys such as the Kidney Transplant Questionnaire. In general, HRQOL assessments improve with transplantation in functional and physical domains. However, many factors actually influence HRQOL in a negative way, including comorbid conditions, kidney function per se, rejection episodes and hospitalizations, employment status, and adverse effects of medications. Perceived physical appearance, issues related to sexuality, stress, anxiety, and even guilt complicate the emotional and psychological landscape after transplantation. This constellation of factors may be predictive of posttransplant life events, such as resumption of employment. Posttransplant HRQOL may be exceedingly important in understanding the issues related to adherence with treatment regimens, especially in the pediatric and adolescent transplant populations. HRQOL is now established as an important issue after transplantation. Nonetheless, shortcomings still exist in our ability to address HRQOL after transplantation. In particular, more study of patient-centered interventions is needed. The use of standardized methodologies for patient assessment could improve our ability to identify if such patient-centered interventions actually succeed across populations, and help us further address the panoply of factors encompassed within posttransplant HRQOL.

Comorbidity↗