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Purpose: The purpose of the study was to characterize differences in donor and recipient relationships between African American (AA) and Caucasian living kidney donors., Methods: Data from all successful living kidney donors at a single institution between 1991 and 2009 were reviewed. Relationships between donor and recipient were categorized and between-group comparisons performed., Results: The study sample consisted of 73 (18%) AA and 324 Caucasian living kidney donors. The distribution of donor-recipient relationships differed significantly between AA and Caucasians. AA donors were more likely to be related to the recipient (88% vs. 74%, p = 0.007) than Caucasians. AA donors were more likely to participate in child to parent donation and were less likely to participate in parent to child donation or to donate to unrelated individuals. Sibling and spousal donations were similar in both groups. Caucasian donors were more likely to be unrelated to the recipient than AA donors., Conclusions: Differences exist in donor-recipient relationships between AA and Caucasian living kidney donors. Future studies exploring cultural differences and family dynamics may provide targeted recruitment strategies for AA and Caucasian living kidney donors. Living unrelated kidney transplantation appears to be a potential growth area for living kidney donation in AA., (© 2011 John Wiley & Sons A/S.)

Introduction: Although African Americans (AA) are considered higher risk kidney donors than Caucasians, limited data are available regarding outcomes of AA donors., Methods: We performed a single-center retrospective review of all kidney donors from 1993 to 2007 and evaluated race/ethnic differences in post-donation changes in renal function, incident proteinuria, and systolic blood pressure (SBP) using linear mixed models., Results: A total of 336 kidney donors (63 AA, 263 Caucasian, 10 other) were evaluated. Before donation, AA had higher serum creatinine concentrations, estimated glomerular filtration rate (GFR) values, and SBP levels than Caucasians. No significant changes in SBP or renal function were observed between the two groups within the first year after donation, although results were limited by incomplete follow-up., Conclusion: AA had higher pre-donation serum creatinine, GFR, and SBP values compared to Caucasians; however, the degree of change in renal function and blood pressure did not differ between groups following kidney donation. Although long-term studies are needed, our study suggests that AA and Caucasians experience similar short-term consequences after donation. The incomplete data available on donor outcomes in our center and in prior publications also indicates a global need to implement systems for structured follow-up of live kidney donors., (© 2009 John Wiley & Sons A/S.)

The demographic factor over age 65 years represents the fastest growing segment of the end-stage kidney disease, wait-listed for kidney transplant, and transplanted populations. As a result, transplant physicians are increasingly asked to evaluate candidacy in older patients. Relatively little attention has been paid to the unique aspects of the pretransplant evaluation in older persons. The natural tendency is to focus on individual comorbidities as isolated entities, such as a history of coronary heart disease, while ignoring factors more specific to the aging process itself. Assessment of the burden of comorbidity along with the application of standardized geriatric assessment tools, such as the measurement of physical and cognitive function, has the potential to refine the pretransplant evaluation process in older kidney transplant candidates., (2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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.

Recurrence of focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome is relatively common after kidney transplantation in young recipients whose predialysis course consists of heavy proteinuria, hypertension and subacute loss of kidney function. The gene(s) mediating this effect remain unknown. We report an unusual circumstance where kidneys recovered from a deceased African American male donor with MYH9-related occult FSGS (risk variants in seven of eight MYH9 E1 haplotype single nucleotide polymorphisms) were transplanted into an African American male child with risk variants in four MYH9 E1 risk variants and a European American female teenager with two MYH9 E1 risk variants. Fulminant nephrotic syndrome rapidly developed in the African American recipient, whereas the European American had an uneventful posttransplant course. The kidney donor lacked significant proteinuria at the time of organ procurement. This scenario suggests that donor-recipient interactions in MYH9, as well as other gene-gene and gene-environment interactions, may lead to recurrent nephrotic syndrome after renal transplantation. The impact of transplanting kidneys from donors with multiple MYH9 risk alleles into recipients with similar genetic background at high risk for recurrent kidney disease needs to be determined.

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.

Background: African Americans (AA) and women are less likely to receive a live kidney donor (LKD) transplant than Caucasians or men. Reasons for non-donation are poorly understood., Methods: A retrospective review of 541 unsuccessful LKD was performed to explore reasons for non-donation and to assess for racial and/or gender differences., Results: We identified 138 AA and 385 Caucasian subjects who volunteered but did not successfully donate. Females (58.2%) were more likely to be excluded than males due to reduced renal function (glomerular filtration rate < 85 mL/min, 7.9% vs. 0.9%, p < 0.0001) or failure to complete the evaluation (6.4% vs. 1.8%, p = 0.01). AA were more commonly excluded due to obesity (body mass index >or= 32 kg/m(2); 30.4% AA vs. 16.6% Caucasian, p = 0.0005) or failure to complete the evaluation (12.3% AA vs. 1.8% Caucasian, p < 0.0001) whereas Caucasians were more often excluded due to kidney stones (1.5% AA vs. 7.3% Caucasian, p = 0.01)., Conclusions: Significantly different reasons for exclusion of LKD exist between potential Caucasian and AA LKD, particularly among women. Among the differences that we observed are potentially modifiable barriers to donation including obesity and failure to complete the donor evaluation. A further understanding of these barriers may help point to strategies for more effective recruitment and successful LKD.

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 < or =3000 cells/mm(3) and neutropenia as an absolute neutrophil count < or =2000/mm(3), 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.

Background: Most reports of donation after cardiac death (DCD) donors are exclusive to kidney transplantation and report high rates of delayed graft function (DGF)., Study Design: From April 1, 2003, to October 3, 2007, we performed 53 kidney transplantations and 4 simultaneous kidney-pancreas transplantations from DCD donors. All DCD donor kidneys were managed with pulsatile perfusion preservation, and all simultaneous kidney-pancreas transplantation donors were managed with extracorporeal support., Results: Of 53 DCD kidney transplantations, 44 (83%) were from standard criteria donors (SCD) and 9 (17%) from expanded criteria donors (ECD). With a mean followup of 12 months, actual patient and kidney graft survival rates were 94% and 87%, respectively. Patient and graft survival rates were 100% in the 4 simultaneous kidney-pancreas transplantations. Incidence of DGF was 57% (60% without versus 20% with extracorporeal support, p = 0.036). Comparison of the 53 DCD donor kidney transplantations with 316 concurrent donation after brain death (DBD) donor adult kidney transplantations (178 SCD, 138 ECD) revealed no differences in demographics or outcomes, except that the DCD donor group had fewer ECDs (17% DCD versus 44% DBD; p = 0.0002), fewer 0-antigen mismatch kidney transplantations (7.5% DCD versus 19% DBD; p = 0.05), and more kidneys preserved with pulsatile perfusion (100% DCD versus 52% DBD; p < 0.0001). Incidences of DGF (57% DCD versus 19% DBD; p < 0.0001) and acute rejection (19% DCD versus 10% DBD; p = 0.10) were higher in the DCD donor group, which resulted in a longer initial length of stay (mean 11 days DCD versus 8.0 days DBD; p = 0.006)., Conclusions: Despite a high incidence of DGF in the absence of extracorporeal support and greater initial resource use, comparable short-term results can be achieved with DCD and DBD donor kidney transplantations.

Objective: To analyze outcomes in simultaneous kidney-pancreas transplantation (SKPT) recipients who retain C-peptide production at the time of SKPT., Methods: This retrospective analysis of SKPTs from January 2002 through January 2007 compared outcomes between patients with absent or low C-peptide levels (<2.0 ng/mL, group A) with those having levels > or =2.0 ng/mL (group B)., Results: Among 74 SKPTs, 67 were in group A and seven in group B (mean C-peptide level 5.7 ng/mL). During transplantation, group B subjects were older (mean age 51 vs 41 years, P = .006); showed a later age of onset of diabetes (median 35 vs 13 years, P = .0001); weighed more (median 77 vs 66 kg, P = .24); had a greater proportion of African-Americans (57% vs 13%, P = .004); and had a longer pretransplant duration of dialysis (median 40 vs 14 months, P = .14). With similar median follow-up of 40 months, death-censored kidney (95% group A vs 100% group B, P = NS) and pancreas (87% group A vs 100% group B, P = NS) graft survival rates were similar, but patient survival (94% group A vs 71% group B, P = .03) was greater in group A. At 1-year follow-up, there were no significant differences in rejection episodes, surgical complications, infections, readmissions, hemoglobin A1C or C-peptide levels, serum creatinine, or MDRD GFR levels., Conclusions: Diabetic patients with measurable C-peptide levels before transplant were older, overweight, more frequently African-American and had a later age of onset of diabetes, longer duration of pretransplant dialysis, and reduced patient survival compared to insulinopenic patients undergoing SKPT. The other outcomes were similar.

Objective: Limited data are available on extended (EX) donor criteria in pancreatic transplantation (PTX)., Methods: This retrospective study from February 2007 through April 2007 compared 2 cohorts of simultaneous kidney-pancreas transplantations (SKPT): the first from EX donors, which were defined as age <10 years or > or =45 years, or donation after cardiac death [DCD]), and the second from conventional (CONV) donors., Results: Among 79 SKPT, 19 (24%) were from EX donors (12 older than age 45 [mean age, 50.2 years], 3 pediatric donors <10, and 4 DCD donors) and the remaining 60 SKPT from CONV donors. The mean donor age was higher in EX than CONV donors (38 vs 25 years, P < .05). There were no other differences between the 2 cohorts. With a similar median follow-up of 29 months, patient, kidney and pancreatic graft survival rates were 89%, 89%, and 79%, for the EX, whereas corresponding outcomes for CONV donors were 93%, 87%, and 80%, respectively (all P = NS). The incidences were similar for delayed kidney graft function (5% in each group), early pancreatic graft loss due to thrombosis (5% EX vs 8% CONV donors), acute rejection (16% EX vs 18% CONV donors), surgical complications, and infections. There were no significant differences in 1-year mean serum creatinine (1.4 mg/dL in each group) or glycohemoglobin (5.2% vs 5.5%) levels between the EX and CONV donor groups, respectively., Conclusion: Short-term outcomes among SKPT from selected EX donors were comparable to CONV donors. Donors at the extremes of age and DCD donors may represent underused resources in SKPT.

Objective: The objective of this study was to review the incidence, risk factors, and impact of bacteremia after pancreas transplantation (PTX)., Methods: We performed a retrospective analysis of consecutive simultaneous kidney-pancreas transplantations (SKPTs) and solitary PTXs from January 2002 through April 2007. Positive blood cultures were correlated with other coexisting infections and parameters., Results: One hundred ten PTXs with enteric drainage included 80 SKPTs and 30 solitary PTXs. Mean follow-up was 32 months. Bacteremia occurred in 29 (26%) patients with 5 (17%) being recurrent; it was seen during the first month after transplantation in 13 (12%), between 1 and 3 months in 12 (11%), between 3 and 12 months in 3 (3%), and after the first year in 3 cases (3%). Typical organisms were as follows: MRSE, MSSE, Klebsiella, Escherichia coli, vancomycin-resistant enterococci (VRE), and Acinetobacteri. Bacteremia was associated with coexisting site infection in 20 cases (69%): deep abdominal wound (31%); line (31%); urinary tract (34%); and pulmonary (7%). Similar bacterial species in blood and a coexisting site occurred in 15 cases (52%). No correlation was seen with cytomegalovirus (CMV) infections. In the first year, bacteremia was associated with more acute rejection episodes (32% vs 17%; P = .09), surgical complications (54% vs 42%; P = .267), mortality (11% vs 4%; P = .15), and death-censored pancreatic (14% vs 9%; P = .39) and kidney (4% vs 0; P = .08) graft loss. Fewer patients with bacteremia received alemtuzumab compared with rATG induction (14% vs 39%; P = .04)., Conclusions: Bacteremias were common within 3 months of PTX. A significant number (39%) were multidrug resistant. The majority were accompanied by abdominal, urinary, or line infections. Bacteremias were associated with slightly higher incidences of rejection, mortality, and graft loss.

Background: In the recent past, advanced age was a contraindication to kidney transplantation (KT). The purpose of this study was to review retrospectively our single center experience in deceased donor (DD) KT with respect to recipient age., Methods: From 10/1/01 to 9/1/06, we performed 356 adult DD KTs. Patients received antibody induction in combination with tacrolimus, mycophenolate mofetil, and tapered steroids., Results: A total of 114 (32%) patients were greater than 60 (including 25 >70 years), 186 (52%) were 40-59 years of age, and 56 (16%) were 19-39 years of age. Of the 114 older patients, 61 (54%) received KTs from expanded criteria DDs (ECD), more than the younger age groups (39% ECDs in patients 40-59 years versus 18% ECDs in patients 19-39 years, P < .0001). Mean waiting time (21 mo) was less for patients greater than 60 years compared with the other 2 groups combined (29 mo, P = .06). Patient survival was 91% in recipients greater than 60 years compared with 95% in those less than 60 years of age (P = NS) with a mean follow-up of 27 mo. Graft survival was similar for all 3 age groups (82% >60 years vs 83% in patients 40-59 years vs 87% in patients 19-39 years, P = NS). Initial and subsequent graft function, morbidity, and resource use were similar among groups. Patient survival [93% ECD vs 89% standard criteria DDs (SCD), P = NS) and graft survival (82% ECD vs 81% SCD, P = NS) rates were similar, whereas mean waiting times (18 mo ECD vs 25 mo SCD, P = .04) were less in patients greater than 60 years who received ECD KTs compared with patients greater than 60 years who received SCD KTs., Conclusions: Patients greater than 60 years account currently for one third of DD KTs performed at our center, and more than half receive kidneys from ECDs. By preferentially directing ECD kidneys to appropriately selected elderly patients, waiting times can be decreased and survival is similar compared with SCD KTs in the elderly. In addition, short-term outcomes can be achieved in patients greater than 60 years that are comparable with those in younger patients.

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.

Background: Expanded criteria donors (ECDs) increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns about diminished survival, poorer renal function, and higher rates of delayed graft function., Study Design: Retrospective analysis of intermediate-term outcomes in ECD kidney transplantations according to method of preservation at a single center using a standardized approach., Results: Over a 5-year period, we performed 141 donations-after-brain-death ECD kidney transplantations into adult recipients. A total of 114 kidneys (81%) were managed with combined cold-storage and pulsatile perfusion preservation (PPP), and the remaining 27 (19%) were preserved with cold storage (CS). The PPP group had a higher proportion of kidneys preserved for longer than 30 hours (28% versus 0, p < 0.001) and a longer mean cold ischemia time (24.5 hours PPP versus 19 hours CS, p < 0.01). Other donor and recipient characteristics were similar between groups. Incidence of delayed graft function was 11% in PPP-stored kidneys versus 37% in CS kidneys (p = 0.002). With a mean followup of 27 months, patient (91% PPP versus 96% CS) and kidney graft survival (81% PPP versus 81.5% CS) rates were comparable. Mean 12-month serum creatinine (1.9 mg/dL) and calculated Modification of Diet in Renal Disease glomerular filtration rate (41 mL/min) values were similar between groups., Conclusions: Despite longer cold ischemia times, recipients of ECD kidneys managed with PPP had similar survival and functional outcomes, but experienced a marked reduction in the rate of delayed graft function.

Background: Dual kidney transplantation (DKT) from donors at the extremes of age represents one approach to expanding the organ donor pool. The purpose of this study was to review our experience with DKT from older donors and en bloc KT (EBKT) from small pediatric donors., Methods: Deceased donor KTs performed at our center between October 2001 and November 2005, were reviewed retrospectively. If the calculated creatinine clearance in an expanded criteria donor was <65 mL/min, then the kidneys were transplanted dually into a single adult recipient. If a pediatric donor weighed <15 kg, then the kidneys were transplanted en bloc. In both instances, low-risk recipients were chosen (primary transplant, low sensitization, body mass index <25 kg/m(2), human leukocyte antigen matching). Donor, recipient, and transplant characteristics, waiting time, and outcomes were examined., Results: Of a total of 279 deceased donor KTs during the 49-month study period, 15 (5%) recipients underwent DKT and 5 (2%) underwent EBKT. Mean donor age was 65.4 years and 21.4 months in the DKT and EBKT groups, respectively. Patient survival rates in both groups were 100% with a mean follow-up of 22 months (minimum, 6 months). Kidney graft survival rates were 80% (12/15) and 60% (3/5) in the DKT and EBKT groups, respectively. The combined incidence of delayed graft function was 10%. Mean 12-month glomerular filtration rates were 46 mL/min and 66 mL/min in the DKT and EBKT groups, respectively., Conclusions: DKT using kidneys from marginal elderly donors and EBKT from small pediatric donors appear to offer a viable option to counteract the shortage of acceptable kidney donors.

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.

Background: The aging donor and recipient population have led to new challenges in kidney transplantation. The purpose of this study was to review retrospectively our single center experience in deceased-donor kidney transplantation, with respect to donor and recipient age., Methods: From October 1, 2001, through February 20, 2004, we performed 144 deceased-donor kidney transplantations, which included 37 procedures (26%) in recipients > or =60 years old and 107 procedures (74%) in recipients 19 to 59 years old. The deceased-donor pool included 57 expanded criteria donors (ECD) and 87 standard criteria donors (defined as not ECD). ECD kidneys were used by matching estimated renal functional mass to recipient size (body mass index, <25 kg/m(2)), which included the use of dual kidney transplantations (n = 9). ECD kidney recipients were further selected on the basis of age >40 years and low immunologic risk. Recipients received rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and steroids., Results: The mean age differed between recipient groups (65 vs 46 years; P < .001). In recipients > or =60 years old, 23 recipients (62%) received kidney transplants from ECDs compared with 34 kidney transplants from ECDs (32%; P < .001) in recipients who were <60 years old. Patient survival was 89% in recipients who were > or =60 years old, compared with 95% in recipients who were <60 years old (P = .11), with a mean follow-up time of 27 months. Kidney graft survival rates were 84% in both recipient groups. Initial and subsequent graft function, rejection, infection, reoperation, length of stay, readmission, and resource use were similar among groups., Conclusion: By the matching of nephron mass with recipient size and avoiding the use of ECD kidneys in recipients with a high immunologic risk, short-term outcomes that are comparable with standard criteria donor kidneys in younger patients can be achieved with either older donors or recipients, regardless of age.

Unlabelled: The purpose of this study was to retrospectively review our experience with "extreme" pancreas donors compared to conventional (CONV) donors., Methods: "Extreme" (EX) pancreas donors were defined as deceased donors (DDs) age >50 years, <8 years, donation after cardiac death (DCD), and targeted for organ discard., Results: From January 2002 through January 2005, we performed 40 simultaneous kidney-pancreas transplants (SKPT) with Thymoglobulin induction, including 9 (22.5%) from EX and 31 from CONV DDs. Mean DD age was higher in EX DD (41.2 years EX vs 26.0 CONV, P < .05), but mean recipient age and cold ischemia times did not differ between groups. With a mean follow-up of 16.8 months in the EX DD group, patient and kidney graft survival rates are both 100%, and the pancreas graft survival rate is 89%. With a mean follow-up of 21.7 months in the CONV DD group, patient and kidney graft survival rates are both 93.5% and the pancreas graft survival rate is 77.4%. All patients with surviving grafts exhibited good initial (1 case of delayed kidney graft function in a CONV DD) and stable long-term kidney and pancreas graft function. Mean length of initial hospital stay and the incidences of acute rejection, readmissions, operative complications, and infections were similar between groups., Conclusions: The results of this study suggest that the limits of donor acceptability continue to evolve as excellent outcomes can be achieved in SKPTs from selected EX DDs.

The purpose of this study was to retrospectively review outcomes in patients undergoing pancreas transplantation (PTX) with a novel induction protocol of alternate-day thymoglobulin (rATG) in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. From January 2002 through January 2005, we performed 55 PTXs in 53 patients. The first dose of rATG (1.5 mg/kg) was given intraoperatively, and subsequent doses were given on alternate days until therapeutic TAC levels (>8 ng/mL) were achieved. All patients underwent PTX with enteric drainage, including 51 with portal and 4 with systemic venous drainage. Patients received a minimum of 2 and maximum of 6 doses of rATG induction (median 3 doses). The patient group had a mean age of 42.8 years and included 40 simultaneous kidney-PTX, 11 sequential PTX after kidney, and 4 PTX-alone transplant recipients. Patient, kidney, and pancreas graft survival rates are 96%, 96%, and 84%, respectively, with a mean follow-up of 21 months. The incidence of acute rejection was 18%; there were no graft losses due to isolated acute rejection. The incidence of infection was 60%, but there were no cases of polyomavirus or Epstein-Barr virus infection and only 6 cases (11%) of cytomegalovirus infection. The composite endpoint of no rejection, graft loss, or mortality was attained by 71% of patients. At present, 94% of surviving patients are both dialysis and insulin-free, including 5 successful PTX retransplants. These findings suggest that PTX with portal-enteric drainage and alternate day rATG induction may result in excellent intermediate-term outcomes.

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.

This study evaluates our initial experience using alemtuzumab induction with rapid corticosteroid elimination in kidney (KTX) and pancreas transplant (PTX) patients. Data were collected retrospectively for all patients who received single-dose alemtuzumab (30 mg IV intraoperatively) with steroid pretreatment and a control group who received alternate day rabbit antithymocyte globulin (rATG) induction with a steroid-based regimen. Patients in both groups received tacrolimus (TAC) and mycophenolate mofetil (MMF). There were 16 patients in each group, including 9 deceased donor KTXs, 5 living donor KTXs, 1 simultaneous K-PTX, and 1 sequential PTX after KTX. Demographic, immunologic, and transplant characteristics were similar between groups. Nine patients (56%) in the alemtuzumab group compared to five (25%) in the control group developed neutropenia requiring MMF or valganciclovir dose reduction (or both). Absolute lymphocyte counts at 3 months were 340 +/- 200/mm3 and 890 +/- 544/ mm3 in the alemtuzumab and control groups, respectively (P = .001). There were two biopsy-proven acute rejection episodes (12.5%) in each group, and no difference in the incidence of infection. Creatinine clearance at 6 months was 58 mL/min in each group. Patient and kidney graft survival rates were both 94% in the alemtuzumab group (one death from cardiac arrest), compared with 100% patient and kidney graft survival rates in the control group (P = NS), with a mean follow-up of 9 and 11 months, respectively. The results of this pilot study suggest that similar short-term outcomes can be achieved using a rapid steroid elimination protocol with alemtuzumab induction therapy compared to rATG with steroids in patients receiving TAC and MMF maintenance therapy.

Introduction: Conversion from calcineurin inhibitor (CI)-based maintenance immunosuppression to sirolimus (SRL)-based immunosuppression may be beneficial in selected renal transplant recipients. The purpose of this study was to evaluate the safety and efficacy of a daclizumab (DAC) bridge protocol in patients converted from CI- to SRL-based maintenance immunosuppression., Methods: We conducted a retrospective chart review of renal transplant recipients who were converted to SRL at least 2 months post-transplant. The protocol consisted of an abrupt discontinuation of either cyclosporin (CsA) or tacrolimus (TAC), initiation of SRL within 48 h of CI discontinuation, and DAC 2 mg/kg at the time of CI discontinuation and again at 14 d (depending on the SRL serum concentration). The SRL starting dose was based on risk stratification in each patient., Results: Twenty-one renal transplant patients were converted to SRL (11 from TAC, 10 from CsA) between October 2001 and July 2003. Conversion occurred at a mean of 23 months post-transplant. Indications for SRL conversion included 12 for chronic allograft nephropathy (CAN), four for CI-associated neurotoxicity, two for thrombotic microangiopathy (TMA), two for post-transplant diabetes mellitus (PTDM), and one for polyomavirus interstitial nephritis (PVN). Mean follow-up was 16 months from time of conversion. Therapeutic SRL levels were reached at a mean of 14 d. Total serum cholesterol levels increased from a mean of 205 (+/- 47) to 234 (+/- 55) mg/dL (P = 0.014), and serum triglyceride levels increased from a mean of 186 (+/- 66) to 257 (+/- 88) mg/dL (P = 0.002). In addition, mean haemoglobin level decreased from 12.0 (+/- 2.3) to 10.5 (+/- 2.1) g/dL (P = 0.002); total white blood cell count decreased from 8300 (+/- 4300) to 4700 (+/- 1400)/mm(3) (P < 0.001); and platelet count decreased from 238 000 (+/- 72 800) to 186 000 (+/- 51 900)/mm(3) (P = 0.002) from before to after conversion. Patients experienced the following side-effects while taking SRL: diarrhoea (n = 6), peripheral oedema (n = 5), arthralgias (n = 4), anaemia (n = 4), oral ulcers (n = 1), deep vein thrombosis (n = 1), shortness of breath (n = 1), and mild increase in serum transaminases (n = 1). Two patients (9.5%) discontinued SRL due to side-effects, both secondary to severe arthralgias. There were two serious infections noted after conversion: one Pseudomonas aeruginosa urosepsis, and one PVN (that was ongoing prior to conversion). Patient survival was 100%, and kidney graft survival was 76%. Five patients (24%) lost their allograft after conversion due to progression of CAN (n = 2), persistent TMA in the kidney (n = 1), patient self-discontinuation of sirolimus (n = 1), and preexisting PVN unresponsive to cidofovir therapy (n = 1). Of the five patients who lost their allograft, the mean serum creatinine at the time of conversion was 3.5 (+/-1.1) mg/dL compared with 2.2 (+/- 0.8) mg/dL in patients who did not lose their allograft (P = 0.034). No acute rejection episodes occurred after conversion to sirolimus., Conclusions: DAC bridge therapy provides safe and effective immunosuppressive coverage while converting renal transplant recipients from CI- to SRL-based maintenance immunosuppressive therapy. A pharmacoeconomic analysis, however, is necessary to determine the cost-effectiveness of this conversion protocol.

More than 1,100 transplants have been performed at WFUBMC, including 60 pediatric transplants and 40 pancreas transplants. The one-year living donor kidney graft survival rate exceeds 90% and the 2 year deceased donor kidney graft survival rate exceeds 80%. The current active waiting list includes more than 300 candidates. Despite more transplants being performed, we continue to under-serve our referral area, which has among the highest rates of hypertension, diabetes, and end stage renal disease in the country. The AOTP has experienced a period of rapid growth over the past 2 years based upon sharing of zero HLA antigen-mismatched kidneys, use of ECD kidneys, liberalization of donor and recipient selection criteria, and the continued development of the pancreas transplant and laparoscopic donor nephrectomy programs. The pancreas transplant program will continue to grow as the waiting list enlarges and matures, with a 200% increase in activity expected within the next few years. The LDKT program will expand as more emphasis is placed on our pretransplant practice, including the more liberal application of laparoscopic donor nephrectomy, which has now become a standard procedure at our WFUBMC is involved in a number of clinical research projects studying new immunosuppressive agents and regimens. In this chapter, we have presented our recent experience with KTX in the elderly, ECD kidneys, alternate day Thymoglobulin administration, valganciclovir prophylaxis, SRL conversion using daclizumab bridge therapy, and pancreas transplantation with portal-enteric drainage. We plan to initiate a number of new protocols in the immediate future, including desensitization of the highly sensitized patient, ABO incompatible transplantation, transplantation of the HIV-positive patient, steroid withdrawal and avoidance regimens, living kidney donation from the anonymous altruistic donor, paired kidney exchanges from living donors, and islet transplantation. WFUBMC remains the most active donor hospital in North Carolina, and a non-heart beating donor protocol has been successfully initiated at our facility. Although much has been accomplished, a number of challenges remain. We look forward to building on our accomplishments, confronting the challenges, and achieving a level of excellence that could only be attained by mutual commitment from a dedicated, multidisciplinary team.

The hypnotic effects of l-tryptophan (1 g), secobarbital (100 mg), and flurazepam (30 mg), relative to placebo, were evaluated in a sample of 54 outpatient chronic insomniacs with a major complaint of sleep maintenance insomnia. Three mutually exclusive complaints about sleep maintenance were identified. Analysis of the data from the tryptophan condition indicated that the single factor type of sleep maintenance complaint accounted for 100% of the variance in a measure reflecting a single overall assessment of tryptophan's hypnotic effect, and 52% of variance in a second, repeated measure assessing subjects' day-to-day experience with the treatment. It is concluded that the distinctions in sleep maintenance insomnia identified are likely to be clinically meaningful. The distinct profiles of the tryptophan responders and nonresponders are described, and the utility of the distinctions in understanding the differential effects of flurazepam and secobarbital discussed. The implications of the finding for a number of sleep disorder-related issues were addressed.

Since 1804 there have been twelve case reports of patients with mood disorders showing a regular periodicity of 48 hours, eight bipolar and four unipolar. This paper describes an additional patient, a 57-year-old man with a 48-hour unipolar cycle. Although his 24-hour serum cortisol pattern was abnormal, there were few clear-cut biological abnormalities. Possible mechanisms are discussed, and comparisons made with previous reports of similar patients.

Rats deprived of D-state sleep (and, to some extent, of slow-wave sleep) for 96 hours show a significant fall in brain acetylcholine in the telencephalon; there were no significant changes in the diencephalon and brain stem. Restraint stress and activity wheel stress produced no significant change in acetylcholine levels in any of these regions; the telencephalic response to sleep deprivation, therefore, cannot be attributed to nonspecific stress. The effects of D-state deprivation and the psychoactive anticholinergic drugs on telencephalic acetylcholine levels are similar.