Erica Hartmann

A Randomized Trial of Alemtuzumab Versus Antithymocyte Globulin Induction in Renal and Pancreas Transplantation

Background. Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction of immunsuppression for kidney and pancreas transplantation, but the two agents have not been compared directly. Methods. We conducted a prospective randomized single-center trial comparing alemtuzumab and rATG induction in adult kidney and pancreas transplantation in patients treated with similar maintenance immunosuppression. Results. Between February 1, 2005, and September 1, 2007, 222 patients randomly received either alemtuzumab (n=113) or rATG (n=109) induction; 180 (81%) underwent kidney alone, 38 (17%) simultaneous pancreas-kidney, and 4 (2%) pancreas after kidney transplants. Of 180 kidney-alone transplants, 152 (84%) were from deceased donors, including 61 (34%) from expanded criteria donors. Retransplantation, human leukocyte antigen match, antibody titer, expanded criteria donors, race, cytomegalovirus status, delayed graft function, and immunologic risks were similar between the two induction groups. With a median follow-up of 2 years (minimum 1 year), overall patient, kidney, and pancreas graft survival rates were 96%, 89%, and 90%, respectively. Survival, initial length of stay, and maintenance immunosuppression (including early steroid elimination) were similar between alemtuzumab and rATG groups, but biopsy-proven acute rejection (BPAR) episodes occurred in 16 (14%) alemtuzumab patients compared with 28 (26%) rATG patients (P=0.02). Late BPAR (>12 months after transplant) occurred in 1 (8%) alemtuzumab patient and 3 (11%) rATG patients (P=NS). Infections and malignancy were similar between the two induction arms. Conclusion. Alemtuzumab and rATG induction therapies were equally safe, but alemtuzumab was associated with less BPAR.

Increased Kidney Transplantation Utilizing Expanded Criteria Deceased Organ Donors with Results Comparable to Standard Criteria Donor Transplant

Objective:To compare outcomes in recipients of expanded criteria donor (ECD) versus standard criteria donor (SCD) kidneys at a single center using a standardized approach with similar immunosuppression. Summary Background Data:Expanded criteria deceased organ donors (ECD) are a source of kidneys that permit more patients to benefit from transplantation. ECD is defined as all deceased donors older than 60 years and donors older than 50 years with 2 of the following: hypertension, stroke as the cause of death, or preretrieval serum creatinine (SCr) greater than 1.5 mg/dl. Methods:We retrospectively studied 90 recipients of adult deceased donor kidneys transplanted from October 1, 2001 to February 17, 2003, including 37 (41%) from ECDs and 53 (59%) from SCDs. ECD kidneys were used by matching estimated renal functional mass to recipient need, including the use of dual kidney transplants (n = 7). ECD kidney recipients were further selected on the basis of older age, HLA-matching, low allosensitization, and low body mass index. All patients received a similar immunosuppressive regimen. Minimum follow up was 9 months. Results:There were significant differences in donor and recipient characteristics between ECD and SCD transplants. Patient (99%) and kidney graft survival (88%) rates and morbidity were similar between the 2 groups, with a mean follow-up of 16 months. Initial graft function and the mean 1-week and 1-, 3-, 6-, 12-, and 18-month SCr levels were similar among groups. Conclusions:The use of ECD kidneys at our center effectively doubled our transplant volume within 1 year. A systematic approach to ECD kidneys based on nephron mass matching and nephron sparing measures may provide optimal utilization with short-term outcomes and renal function comparable to SCD kidneys.

Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation: A Spectrum or Specter of Quality?

Objective:To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data:Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods:Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results:ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. Conclusions:By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants.

Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness

Background. Clinical data are lacking concerning concomitant administration of everolimus and tacrolimus in renal transplant recipients. Methods. In a prospective, multicenter, open-label, exploratory, randomized, 6-month study, 92 de novo renal transplant patients received everolimus, steroids, and basiliximab with low or standard tacrolimus exposure. The primary objective was to compare renal function at 6 months after transplant. Results. Mean 6-month serum creatinine (primary safety variable) was 112±31 &mgr;mol/L (1.26±0.35 mg/dL) and 127±50 &mgr;mol/L (1.44±0.57 mg/dL) in the low and standard tacrolimus groups, respectively, (n.s.); mean estimated GFR (Nankivell) was 75.3±16.6 mL/min and 72.5±15.2 mL/min (n.s.). Biopsy-proven acute rejection occurred in 13 patients: seven (14%) in the low tacrolimus group and six (14%) in the standard tacrolimus group, n.s. One graft was lost in the standard tacrolimus group. No patients died. Conclusions. Tacrolimus exposure reduction in the presence of everolimus, steroids and basiliximab induction results in good efficacy in de novo renal transplant recipients with very well-preserved renal function. Additional studies are warranted because between-group comparisons were limited by the relatively small differences in tacrolimus exposure in the 2 arms; trough levels were toward the upper end of the low-exposure ranges and toward the bottom of the standard-exposure ranges.

Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post-transplant outcomes.

Singh RP, Farney AC, Rogers J, Zuckerman J, Reeves‐Daniel A, Hartmann E, Iskandar S, Adams P, Stratta RJ. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes. 
Clin Transplant 2011: 25: 255–264.

Physical Function in Older Candidates for Renal Transplantation: An Impaired Population

BACKGROUND AND OBJECTIVES Although physical function is a major determinant of health outcomes and quality of life in older adults, standard tools for its assessment have not been routinely applied to the fastest growing segment of the kidney transplant candidate population, which is at high risk of comorbidity and disability--people over age 60. The objective of this study was to describe the baseline physical function in older adults with renal failure referred for transplantation and compare them with older adults with other significant comorbidity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS An observational sample comparing physical performance in renal transplant candidates over age 60 (Renal Failure) to older people with diastolic heart failure (Heart Failure), chronic obstructive pulmonary disease (COPD), or at high risk for cardiovascular disease (High CV Risk) was studied. RESULTS Older people with Renal Failure were significantly impaired by objective measures of physical function, including lower Short Physical Performance Battery, slower gait speed, and lower grip strength. CONCLUSIONS Older people referred for renal transplantation had poorer physical performance than older adults with other common chronic diseases and may be at high risk for disability while awaiting transplantation.

Health insurance status of US living kidney donors

BACKGROUND AND OBJECTIVES Ensuring follow-up of living kidney donors (LKDs) is essential to long-term preventive care. We sought information on health insurance status of US LKDs, with particular attention to age, gender, and ethnicity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The United Network for Organ Sharing/Organ Procurement Transplantation Network database was queried for associations among age at donation, race, gender, and health insurance status. We studied all US LKDs between July 2004 and September 2006. RESULTS A total of 10,021 LKDs with known health insurance status were studied, 1765 (18%) of whom lacked health insurance at donation. There were 4852 donors without health insurance information. Younger kidney donors had higher rates of being uninsured (age 18 to 34: 26.2%; age 35 to 49: 15.2%; age 50 to 64: 11.2%; age >65: 3.8%; P < 0.0001), as did men (19.5 versus 16.3% for women; P < 0.0001), and ethnic minorities (white 13.4%, black 21%, Hispanic 35.6%, Asian 26.7%; P < 0.0001). CONCLUSIONS This study confirms that younger patients, ethnic minorities, and men are less likely to have health insurance when donating a kidney, which could negatively affect adherence to long-term follow-up.

Optimal everolimus concentration is associated with risk reduction for acute rejection in de novo renal transplant recipients.

Background. Everolimus (Evl) plus tacrolimus (Tac) in de novo renal transplantation is effective and safe. Whether the concentration of Evl affects efficacy and safety in a Tac-based regimen has not been previously reported. Aim. To evaluate whether the concentration of Evl affects biopsy-proven acute rejection (BPAR), renal function, adverse events (AEs); and to assess for pharmacokinetic (PK) interactions. Methods. Data were from a prospective, multicenter, open-label, randomized, exploratory 6-month study of 92 renal transplant patients treated de novo with concentration-controlled Evl (target trough levels ≥3 ng/mL) plus low-dose Tac or Evl plus standard-dose Tac; both groups received basiliximab and corticosteroids. Data were pooled across study arms to examine BPAR rates in patients with Evl trough levels less than 3 (n=26), 3 to 8 (n=62), or more than 8 ng/mL (n=4). Groups were stratified by both Evl and Tac trough levels to evaluate glomerular filtration rate and AEs. Evl and Tac PK interactions were evaluated in a subset of 14 patients. Results. Evl trough level of more than or equal to 3 ng/mL was associated with significantly lower rates of BPAR as compared with a trough level of less than 3 ng/mL. Glomerular filtration rate was similar at 6 months for both the low and standard Tac groups. No apparent PK interactions were observed between Evl and Tac. AEs were infrequent and did not seem to be associated with the Evl or Tac level. Conclusions. Evl trough levels ≥3 ng/mL plus Tac are associated with low rates of BPAR without adversely affecting renal function. No evident PK interaction exists between Evl and Tac.

Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors.

Background. The purpose of this study was to perform a case-matched cohort analysis of dual kidney transplantation (DKT) from expanded criteria donors (ECDs) compared to single kidney transplantation (SKT) from concurrent ECDs and standard criteria donors (SCDs, defined as non-ECD). Methods. Deceased donor (DD) kidney transplants (KTs) performed at a single center between October 2001 and February 2006 were reviewed retrospectively. If the calculated DD creatinine clearance (CrCl) was <65 mL/min, then the kidneys were transplanted dually into a single patient. In the case of DKT and SKT from ECDs, low risk patients were chosen and informed consent was obtained. Patients in each group were matched for age, gender, race, transplant number, and time of transplant. Results. Of 294 adult DD KTs performed, 16 (5%) were DKTs, which were matched with 16 concurrent SCD and 16 ECD SKT patients. Mean donor age in years (65 DKT vs. 33 SCD vs. 61 ECD; P<0.0001) and mean donor CrCl in ml/min (54 DKT vs. 91 SCD vs. 76 ECD; P=0.002) were different between groups. Patient survival was 100% in the DKT and SCD SKT groups and 94% in the ECD SKT group (mean follow up 23–28 months); graft survival rates in the DKT, SCD, and ECD groups were 81%, 81%, and 94%, respectively (P=NS). Graft function, rejection, and morbidity were similar between groups. Conclusions. DKT using kidneys from marginal ECDs is a viable option to counteract the growing shortage of available organs. Excellent short-term results and renal function can be achieved with older, low nephron mass donors provided that both kidneys are transplanted into a single recipient.

Management of leukopenia in kidney and pancreas transplant recipients

Abstract:  Leukopenia is frequently observed in the setting of solid organ transplantation. The risk factors, natural history, and outcomes associated with leukopenia post‐transplantation have not been well defined. We retrospectively studied 102 adult kidney and/or pancreas transplant recipients over a one‐yr period of time. By defining leukopenia as a white blood cell count ≤3000 cells/mm3 and neutropenia as an absolute neutrophil count ≤2000/mm3, the combined incidence of either leukopenia or neutropenia was 58% (59/102); the first episode occurred at a mean of 91 d post‐transplant. A significant increase in the incidence of leukopenia was found in patients who either received alemtuzumab induction (42% with alemtuzumab vs. 9% with rabbit anti‐thymocyte globulin induction, p < 0.05) and/or had rapid steroid withdrawal in the early post‐transplant period (44% with vs. 16% without steroid withdrawal, p < 0.05). The most common intervention performed for leukopenia was reducing the dose of mycophenolate mofetil and/or valganciclovir. When granulocyte stimulating factors were used, a mean of 3.1 doses were needed to successfully manage the leukopenia. Although leukopenia was a common finding in our study of kidney and/or pancreas transplant recipients, there was no difference in the rates of infection or acute rejection in patients with and without leukopenia.