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J Harold Helderman

Publications and source records attributed to J Harold Helderman.

At least 19 recordsLinked to original sources

Polyclonal antibody-induced serum sickness in renal transplant recipients: treatment with therapeutic plasma exchange.

Serum sickness is an immune-complex mediated illness that frequently occurs in patients after polyclonal antibody therapy (ATGAM or thymoglobulin). Serum sickness presents with significant morbidity but is self-limited and resolves with prolonged steroid therapy. We present five renal transplant patients who developed serum sickness after polyclonal antibody treatment with severe symptoms that persisted after being started on systemic steroids. These patients underwent one or two courses of therapeutic plasma exchange (TPE) with subsequent complete resolution of their symptoms. Renal transplant recipients with serum sickness after polyclonal antibody therapy may benefit from TPE by accelerating their time to recovery and thereby reducing overall morbidity.

Adult↗

Screening asymptomatic diabetic patients for coronary artery disease prior to renal transplantation.

BACKGROUND: Coronary artery disease (CAD) is a significant contributor to excess mortality in renal transplant candidates with diabetes mellitus (DM). Prior studies relating to risk stratification for significant CAD in diabetics are confined to Caucasian type 1 DM patients. METHODS: To assess the prevalence of clinically silent CAD and to identify variables that are associated with CAD, we retrospectively analyzed the cardiac catheterization data of 97 asymptomatic type 1 and 2 DM kidney and kidney-pancreas transplant candidates. RESULTS: Thirty-three percent of type 1 and 48% of type 2 DM patients had significant stenosis (> or = 70%) in 1 or more coronary arteries. On multivariate logistic regression analysis, body mass index (BMI) >25 was significantly associated with CAD (relative risk = 4.8, P = 0.002). The age of the patient (7% increase in risk/year, P = 0.01; or relative risk = 3.0 if age >47 years, P = 0.032) and smoking history (2% increase in risk/pack-year of smoking, P = 0.10) were also associated with CAD. African American patients, who comprised 30% of the sample, had a 71% lower risk compared with Caucasian patients (P = 0.03). Factors that were not significantly associated with CAD included gender, type of diabetes, and whether dialyzed for >6 months prior to catheterization. CONCLUSIONS: We conclude that a notable proportion (approximately one-third to one-half) of asymptomatic type 1 and type 2 diabetic renal transplant candidates have significant CAD. Additionally, young African American DM patients with no smoking history and a BMI </=25 are at reduced risk, and invasive tests may not be necessary in this group.

Adult↗

Potential clinical implications of substitution of generic cyclosporine formulations for cyclosporine microemulsion (Neoral) in transplant recipients.

Cyclosporine (CsA) is a critical-dose drug for which a minor change in absorption can have important clinical implications. Generic formulations of CsA are becoming more widely available, but standard criteria for bioequivalence require only that a single study in healthy volunteers demonstrate that mean pharmacokinetic parameters fall within 80-125% of the mean values for Neoral, the reference formulation of CsA. However, CsA absorption is known to differ between healthy volunteers and transplant patients and between different types of transplant patients, such that standard bioequivalence testing may be inadequate to ensure interchangeability of CsA formulations in all patients. The limited available clinical evidence has shown that stable renal transplant patients receiving Neoral have a significant reduction in mean CsA trough level after transfer to the Cicloral formulation. Mean pharmacokinetic values have been reported as equivalent following transfer to Gengraft in one study, but mean CsA trough fell and mean serum creatinine rose significantly in a separate trial. The only clinical outcomes data available are from a retrospective study of de novo renal transplant patients, which reported a significantly higher incidence of biopsy-proven acute rejection in patents receiving Gengraf versus Neoral (39% versus 25%, P<0.05). Until robust clinical data demonstrate that different formulations of CsA are interchangeable, it is advisable to prescribe CsA by brand, and any transfer to a different CsA formulation should be undertaken with close supervision and only at the direction of the transplant physician.

Animals↗

Living donor kidney transplantation in a Veterans Administration medical center.

BACKGROUND: A shortage of organ donors remains the major limiting factor in kidney transplantation. Living donor renal transplantation, especially living-unrelated donors, may expand the donor pool by providing another source of excellent grafts. METHODS: Between 1983 and 2003, 109 living donor kidney transplants were performed. Potential donors were assessed with a standardized routine. Antithymocyte serum (N-ATS) and Basiliximab were used as induction agents. Sandimmune, Gengraf, Neoral, and Prograf were the main immunosuppressants with Immuran, Mycophenolate Mofetil, and steroids. Eighty-two percent of the recipients were from out of state. RESULTS: Seventy-eight percent of the living donors were from living-related donors and 22% were from living-unrelated donors. One- and three-year patient survival rates were 97.6% and 93.2% with 1- and 3-year graft survival rates of 93.2% and 88.3%, respectively. There were 6 delayed graft functions (5.5%), 16 acute cellular rejections (10%), and 10 chronic rejections (9%). Twelve patients died, 7 of them with a functioning graft. In the past 6 years (1997-2003), the number of living donor kidney transplants surpassed deceased donor kidney transplants. CONCLUSIONS: Because of the limited number of cadaveric kidneys available for transplant, living donors represent a valuable source, and the use of living-unrelated donors has produced an additional supply of organs. In our program, the proportion of living donors used for kidney transplant is comparable with other non-Veterans Administration programs and the survival of these allografts appears to be superior to deceased donor kidney transplants.

Female↗

Recurrent lupus nephritis in renal transplant recipients revisited: it is not rare.

BACKGROUND: Although recurrent lupus nephritis (RLN) after kidney transplantation is reported to be rare (1%-4%), recent studies suggest a higher incidence. The purpose of this study was to determine the incidence of RLN in a large cohort of renal transplant recipients with systemic lupus erythematosus (SLE). METHODS: The records of 54 renal transplant recipients with SLE were reviewed. Thirty-one patients underwent biopsy because of worsening renal function and proteinuria. All biopsy specimens were evaluated by light microscopy, immunofluorescence (IF), and electron microscopy (EM). RESULTS: Among the 50 patients with at least 3 months of follow-up, RLN was present in 15 (52% of patients who underwent biopsy, 30% of total patients): mesangial lupus nephritis (LN) (class II) in eight, focal proliferative LN (class III) in four, and membranous LN (class Vb) in three patients. One patient had graft loss because of RLN (class II) at 10.5 years. The duration of dialysis before transplantation was not different between patients with RLN compared to patients without RLN (P=0.40). Overall patient survival (n=50) was 96% at 1 year and 82% at 5 years, and graft survival was 87% at 1 year and 60% at 5 years. Graft survival was worse in patients who underwent biopsy compared with patients who never underwent biopsy (P<0.01). CONCLUSIONS: RLN is more common than previously reported, but in our series, graft loss because of RLN was rare. Aggressive use of allograft biopsies and morphologic evaluation with IF and EM are important factors in the diagnosis of RLN. The impact of new immunosuppressive agents on the incidence of RLN remains to be seen.

Adult↗

Effects of diabetes and cadaveric organs on functional performance and health-related quality of life after kidney transplantation.

BACKGROUND: The current study was undertaken to identify factors specific to kidney transplantation that are associated with posttransplant functional performance (FP) and health-related quality of life (HRQOL). METHODS: Karnofsky FP status was assessed longitudinally in 86 adult kidney transplant recipients. Patients reported HRQOL using the Short Form-36 (SF-36) health survey and the Psychosocial Adjustment to Illness Scale (PAIS). RESULTS: FP improved (P <0.001) after kidney transplantation (from 75 +/- 1 to 77 +/- 1, 81 +/- 1, and 82 +/- 1 at 0, 3, 6, and 12 months, respectively). Patients receiving organs from living donors showed continued improvement through posttransplant year 1 while those receiving cadaveric organs stabilized at month 6 (simple interaction contrast, year 1 versus pretransplant; P <0.05). Patients receiving dialysis therapy for 6 months or more prior to transplantation demonstrated lower SF-36 posttransplant physical component scores in comparison with patients who were transplanted preemptively (38 +/- 1 versus 45 +/- 2, P <0.05). Path analysis demonstrated the positive direct effect of time on FP with kidney transplantation (beta = 0.23, P <0.05), and the negative direct effects on FP of diabetes (beta = -0.22) and cadaveric organs (beta = -0.22, both P <0.05). In turn, FP had a positive direct effect on HRQOL (beta = 0.40, P <0.001). CONCLUSIONS: Overall improvement in FP is attenuated 1 year after kidney transplantation in recipients of organs from cadaveric donors. The positive effect of time after transplantation, and the negative effects of cadaveric organs and diabetes on posttransplant HRQOL, are indirect and are mediated by the direct effects of these variables on posttransplant FP.

Adult↗

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↗

A pilot protocol of a calcineurin-inhibitor free regimen for kidney transplant recipients of marginal donor kidneys or with delayed graft function.

UNLABELLED: The worsening shortage of cadaver donor kidneys has prompted use of expanded or marginal donor kidneys (MDK), i.e. older age or donor history of hypertension or diabetes. MDK may be especially susceptible to calcineurin-inhibitor (CI) mediated vasoconstriction and nephrotoxicity. Similarly, early use of CI in patients with delayed graft function may prolong ischaemic injury. We developed a CI-free protocol of antibody induction, sirolimus, mycophenolate mofetil, and prednisone in recipients with MDK or DGF. METHODS: Adult renal transplant recipients who received MDK or had DGF were treated with a CI-free protocol consisting of antibody induction (basiliximab or thymoglobulin), sirolimus, mycophenolate mofetil, and prednisone. Serial biopsies were performed for persistent DGF. Patients were followed prospectively with the primary endpoints being patient and graft survival, biopsy-proven acute rejection, and sirolimus-related toxicity. RESULTS: Nineteen recipients were treated. Mean follow-up was 294 days. Actuarial 6- and 12-month patient survival was 100% and 100% and graft survival was 93% and 93%, respectively. The only graft loss was due to primary non-function (PNF). The incidence of AR was 16%. Mean serum creatinine at last follow-up was 1.6 mg/dL. Sirolimus-related toxicity included lymphocele (1), wound infection (2), thrombocytopenia (1). and interstitial pneumonitis (1). CONCLUSION: A CI-free protocol with antibody induction and sirolimus results in low rates of AR and PNF and excellent early patient and graft survival in patients with MDK and DGF. CI-free protocols may allow expansion of the kidney donor pool by encouraging utilization of MDK at high risk for DGF or CI-mediated nephrotoxicity.

Adult↗

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↗