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Bruce Kaplan

Publications and source records attributed to Bruce Kaplan.

At least 19 recordsLinked to original sources

Successful rescue of refractory, severe antibody mediated rejection with splenectomy.

Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.

Adult↗

Why hasn't eliminating acute rejection improved graft survival?

Although patients with end-stage renal disease can be maintained with dialysis therapy, the superiority of patient survival with renal transplantation makes transplantation the preferred method of renal replacement. Potent immunosuppressive therapies, particularly calcineurin inhibitors, have greatly reduced the incidence of acute rejection. However, long-term allograft survival remains limited. We discuss the impact of acute rejection on long-term allograft survival and discuss other factors leading to late allograft loss, including calcineurin inhibitor toxicity, chronic allograft nephropathy, and BK virus nephropathy, as well as donor and recipient factors associated with long-term allograft loss.

Delayed Graft Function↗

The expectancies of living kidney donors: do they differ as a function of relational status and gender?

BACKGROUND: While two-thirds of the living kidney donors continue to be genetically related to the recipient, there has been a 300% increase in unrelated living donors over the last 10 years. Also, women continue to represent more than half of all the living kidney donors. This study examined whether donor expectancies varied as a function of relational status or gender. METHODS: 362 kidney donor candidates (232 related, 130 unrelated) completed the Living Donation Expectancies Questionnaire (LDEQ). A 2 (relational status: related or unrelated) x 2 (gender: male or female) multivariate analysis of variance was conducted to examine main and interaction effects across the six domains of the LDEQ: interpersonal benefit (IB), personal growth (PG), spiritual benefit (SB), quid pro quo (QPQ), health consequences (HC) and miscellaneous consequences (MC). RESULTS: The highest expectancies were for PG (54.1%) and IB (29.8%), followed by expectations of MC (18.2%), SB (16.9%), HC (14.4%), and QPQ (4.4%). Multivariate analyses showed a relational main effect [F = 4.18, P = 0.02] and a gender main effect [F = 5.09, P = 0.01]. Subsequent univariate analyses showed significant effects (P<0.05) for IB (related>unrelated), QPQ (men>women), HC (unrelated>related, men > women) and MC (unrelated > related). CONCLUSION: Overall, donor candidate expectancies appear to be realistic in light of previous findings of donor benefit. However, some living donor expectancies may vary as a function of donor relational status and gender. It may be important to assess and appropriately address both positive and negative expectancies at the time of donor evaluation. The LDEQ may be a useful clinical tool for assessing such expectancies.

Adult↗

Overcoming barriers to long-term graft survival.

Although short-term kidney graft survival has improved in recent years, the focus has shifted to the challenge of improving long-term graft survival. Acute rejection, chronic allograft nephropathy, and cardiovascular disease are associated with graft loss and patient death. Reducing the potential for such posttransplantation complications may improve long-term graft survival. In addition, gaining a better understanding of the role that various immunosuppressive therapies have in decreasing the risk for graft injury will help clinicians make better-informed decisions about appropriate treatment regimens for individual kidney transplant recipients.

Acute Disease↗

Therapeutic drug monitoring of mycophenolate mofetil in transplantation.

A roundtable meeting to discuss the use of therapeutic drug monitoring (TDM) to guide immunosuppression with mycophenolate mofetil was held in New York in December 2004. Existing recommendations for the initial months after transplantation were updated. After ensuring adequate levels of mycophenolic acid (MPA, the active metabolite of mycophenolate mofetil) immediately after transplantation, optimal efficacy may require only a few dose adjustments, because intrapatient variability in exposure seems low. Recommendations based on current knowledge were made for posttransplantation sampling time points and for target MPA concentrations. Algorithms for estimating MPA exposure using limited sampling strategies were presented, and a new assay for MPA discussed. It was agreed that because of interpatient variability and the influence of concomitant immunosuppressants, TDM might help optimize outcomes, especially in patients at higher risk of rejection. The value of TDM in the general transplant population will be assessed from large, ongoing, randomized studies.

Algorithms↗

Treating tobacco use and dependence in kidney transplant recipients: development and implementation of a program.

Tobacco use adversely affects transplant outcomes such as graft survival, patient survival, and other conditions that alter transplant patient longevity. Especially concerning is tobacco's relationship to cardiovascular disease, the number 1 cause of death in kidney transplant recipients. Many authors conclude that tobacco interventions ought to be provided to patients and sometimes lament that there are no tobacco dependence interventions designed for kidney transplant recipients. European Best Practice Guidelines for Renal Transplantation also support tobacco dependence interventions. The purpose of this article is to describe one institution's experience in implementing the clinical practice guideline for treating tobacco use and dependence within a kidney and pancreas transplant program.

Algorithms↗

Patient-reported outcomes for open versus laparoscopic living donor nephrectomy.

BACKGROUND: Rates of living kidney donation have increased dramatically in recent years, in large part because of improved surgical techniques such as laparoscopic nephrectomy. OBJECTIVE: To compare patient-reported outcomes of laparoscopic nephrectomy versus open donor nephrectomy in 84 adult live kidney donors. OUTCOME MEASURES: Outcomes included perceptions of pain and surgical scarring, number of surgical/medical complications, hospital length of stay, physical health problems related to donation, return to work, financial impact, health-related quality of life, and satisfaction with the donation experience. RESULTS AND CONCLUSION: The 2 groups did not differ significantly in pain perceptions, number of surgical/medical complications, physical health problems, financial impact, health-related quality of life, or overall satisfaction. However, laparoscopic nephrectomy donors had significantly fewer hospital days and faster return to work time than open donor nephrectomy donors. The majority of donors report excellent health-related quality of life and no complications in the months following surgery. In addition, it appears that laparoscopic nephrectomy, in comparison to open donor nephrectomy, may reduce barriers to living kidney donation by reducing hospital length of stay and time away from work. Being able to return to work much sooner after surgery may significantly reduce the indirect costs (ie, lost wages) associated with living donation.

Adult↗

Do report cards influence hospital choice? The case of kidney transplantation.

The national program to report hospital-level outcomes for transplantation has been in place since 1991, yet it has not been addressed in the existing literature on hospital report cards. We study the impact of reported outcomes on demand at kidney transplant centers. Using a negative binomial regression with hospital fixed effects, we estimate the number of patients choosing each center as a function of reported outcomes. Parameters are identified by the within-hospital variation in outcomes over five successive report cards. We find some evidence that report cards influence younger and college-educated patients, but, overall, report cards do not affect demand.

Choice Behavior↗

The impact of mycophenolate mofetil on long-term outcomes in kidney transplantation.

Mycophenolate mofetil (MMF) has been used in kidney and pancreas transplantation for almost 10 years. In the pivotal phase III trials, MMF use was accompanied by a dramatic reduction of rejection rates in kidney transplantation; however, the impact on graft and patient was undetermined. Analyses of the United States Renal Data System and the Scientific Registry of Transplant Recipients databases later provided a valuable measure of the impact of MMF in improving outcomes. In this review, we provide a synopsis of the prospective studies, including but not limited to the pivotal MMF approval trials, and analyses of the national transplant registries relevant to the long-term impact of MMF in kidney transplantation. Indeed, a substantial body of evidence has shown MMF treatment improves patient survival, graft survival, and death-censored graft survival in kidney transplantation. The beneficial effects of MMF have been particularly notable in high-risk recipients such as African Americans. In coming years, these benefits will require reevaluation in the context of the growing use of novel protocols combining MMF with tacrolimus or sirolimus.

Black or African American↗

Access to quality: evaluation of the allocation of deceased donor kidneys for transplantation.

Disparities in both access to the kidney transplant waiting list and waiting times for transplant candidates have been extensively documented with regard to ethnicity, gender, socioeconomic factors, and region. However, the issue of access to equivalent quality organs has garnered less attention. The principal aim of this study was to determine whether certain patient populations were more likely to receive lower quality organs. This was a retrospective cohort study of all deceased-donor adult renal transplant recipients in the United States from 1996 to 2002 (n = 45,832). Using previously reported categorization of donor quality (I to V), the propensity of transplant recipients to receive lower-quality kidneys in a cumulative logit model was evaluated. Older patients were progressively more likely to receive lower-quality organs (age > or = 65 yr, odds ratio [OR] = 2.1, P < 0.01) relative to recipients aged 18 to 24 yr. African American and Asian recipients had a greater likelihood of receiving lower-quality organs relative to non-Hispanic Caucasians. Regional allocation networks were highly variable with regard to donor quality. Neither recipient gender (OR = 1.00, P = 0.81) nor patient's primary diagnosis were associated with donor quality. Findings suggest that disparities in the quality of deceased donor kidneys to transplant recipients exist among certain patient groups that have previously documented access barriers. The extent to which these disparities are in line with broad policies of equity and potentially modifiable will have to be examined in the context of allocation policy.

Adult↗

Randomized calcineurin inhibitor cross over study to measure the pharmacokinetics of co-administered enteric-coated mycophenolate sodium.

Enteric-coated mycophenolate sodium (EC-MPS) (myfortic) is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal adverse events by delaying the release of MPA until the small intestine. A randomized, calcineurin inhibitor crossover, steady-state pharmacokinetic study in stable renal transplant patients receiving EC-MPS demonstrated increased MPA exposure of 19% higher, MPA C(max,ss) 19% lower and MPA C(min,ss) approximately twofold higher with tacrolimus, than cyclosporine microemulsion. No study drug-related adverse events were recorded, but mean blood glucose concentration was higher in patients receiving tacrolimus (p = 0.031). The dose changes in relation to MPA exposure in patients is dependent on the clinical situation and may not always be warranted. These observations should be taken into consideration when switching from one calcineurin inhibitor to another, but the final dosage should be based on both this pharmacokinetic data and the clinical situation.

Adult↗

The effects of renal transplantation on peripheral blood dendritic cells.

Recent advances allow accurate quantification of peripheral blood (PB) myeloid and plasmacytoid dendritic cell (DC) populations (mDC and pDC, respectively), although the response to renal transplantation (RT) remains unknown. Using flow cytometry, PBDC levels were quantified in patients with end stage renal disease (ESRD) undergoing RT. PBDC levels were significantly reduced in ESRD patients pre-RT compared to healthy controls, with further reduction noted immediately following a hemodialysis session. RT resulted in a dramatic decrease in both subsets, with a greater reduction of pDC levels. Both subset levels were significantly lower than in control patients undergoing abdominal surgery without RT. Subgroup analysis revealed significantly greater mDC reduction in RT recipients receiving anti-lymphocyte therapy, with preferential binding of antibody preparation to this subset. Samples from later time points revealed a gradual return of PBDC levels back to pre-transplant values concurrent with overall reduction of immunosuppression (IS). Finally, PBDC levels were significantly reduced in patients with BK virus nephropathy compared to recipients with stable graft function, despite lower overall IS. Our findings suggest that PBDC levels reflect the degree of IS in renal allograft recipients. Furthermore, PBDC monitoring may represent a novel strategy to predict important outcomes such as acute rejection, long-term graft loss and infectious complications.

Adult↗

Pharmacokinetic principles of immunosuppressive drugs.

A basic tenet of clinical pharmacology is that the pharmacologic activity of an exogenously administered agent is related to the free drug concentration available at its receptor or ligand-binding site. The discipline of pharmacokinetics can be defined as the study of the processes that lead to the availability of an agent to its site of action. In this review we will discuss basic principles of pharmacokinetics that govern the absorption, distribution, metabolism, elimination and binding of immunosuppressive drugs commonly utilized in whole organ transplantation. In a discipline such as organ transplantation, where the agents utilized carry significant toxicity and where failure of efficacy can have dire consequences, knowledge of the pharmacokinetics of the agents utilized has become a basic skill for all transplant professionals. In this review we describe some of the underlying principles that govern the disposition of the agents commonly utilized in solid organ transplantation. In addition, we hope this review will help in understanding some of the basic drug interactions encountered in transplant practice.

Biological Availability↗

The broad spectrum of quality in deceased donor kidneys.

The quality of the deceased donor organ clearly is one of the most crucial factors in determining graft survival and function in recipients of a kidney transplant. There has been considerable effort made towards evaluating these organs culminating in an amendment to allocation policy with the introduction of the expanded criteria donor (ECD) policy. Our study, from first solitary adult deceased donor transplant recipients from 1996 to 2002 in the National Scientific Transplant Registry database, presents a donor kidney risk grade based on significant donor characteristics, donor-recipient matches and cold ischemia time, generated directly from their risk for graft loss. We investigated the impact of our donor risk grade in a naive cohort on short- and long-term graft survival, as well as in subgroups of the population. The projected half-lives for overall graft survival in recipients by donor risk grade were I (10.7 years), II (10.0 years), III (7.9 years), IV (5.7 years) and V (4.5 years). This study indicates that there is great variability in the quality of deceased donor kidneys and that the assessment of risk might be enhanced by this scoring system as compared to the simple two-tiered system of the current ECD classification.

Adolescent↗