Paul E. Morrissey

Donor kidney exchanges.

Kidney transplantation from live donors achieves an excellent outcome regardless of human leukocyte antigen (HLA) mismatch. This development has expanded the opportunity of kidney transplantation from unrelated live donors. Nevertheless, the hazard of hyperacute rejection has usually precluded the transplantation of a kidney from a live donor to a potential recipient who is incompatible by ABO blood type or HLA antibody crossmatch reactivity. Region 1 of the United Network for Organ Sharing (UNOS) has devised an alternative system of kidney transplantation that would enable either a simultaneous exchange between live donors (a paired exchange), or a live donor/deceased donor exchange to incompatible recipients who are waiting on the list (a live donor/list exchange). This Regional system of exchange has derived the benefit of live donation, avoided the risk of ABO or crossmatch incompatibility, and yielded an additional donor source for patients awaiting a deceased donor kidney. Despite the initial disadvantage to the list of patients awaiting an O blood type kidney, as every paired exchange transplant removes a patient from the waiting list, it also avoids the incompatible recipient from eventually having to go on the list. Thus, this approach also increases access to deceased donor kidneys for the remaining candidates on the list.

Preemptive Plasmapheresis and Recurrence of FSGS in High‐Risk Renal Transplant Recipients

Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is ascribed to the presence of a circulating FSGS permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This study addressed the efficacy of pre‐transplant PP in decreasing the incidence of recurrence in high‐risk patients. Ten patients at high‐risk for FSGS recurrence because of rapid progression to renal failure (n = 4) or prior transplant recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri‐operative period. Recurrences were identified by proteinuria >3 g/day and confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6 with prior recurrence, were free of recurrence at follow‐up (238–1258 days). Final serum creatinine in 8 patients with functioning kidneys averaged 1.53 mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior transplants to recurrent FSGS. Two of these progressed to end‐stage renal disease (ESRD) and the third has significant renal dysfunction. Based on inclusion criteria, recurrence rates of 60% were expected if no treatment was given. Therefore, PP may decrease the incidence of recurrent FSGS in high‐risk patients. Definitive conclusions regarding optimal management can only be drawn from larger, randomized, controlled studies.

Donation after circulatory death: current practices, ongoing challenges, and potential improvements.

Organ donation after circulatory death (DCD) has been endorsed by the World Health Organization and is practiced worldwide. This overview examines current DCD practices, identifies problems and challenges, and suggests clinical strategies for possible improvement. Although there is uniform agreement on DCD donor candidacy (ventilator-dependent individuals with nonrecoverable or irreversible neurologic injury not meeting brain death criteria), there are variations in all aspects of DCD practice. Utilization of DCD organs is limited by hypoxia, hypotension, reduced – then absent – organ perfusion, and ischemia/reperfusion syndrome. Nevertheless, DCD kidneys exhibit comparable function and survival to donors with brain death kidneys, although they have higher rates of primary graft nonfunction, delayed graft function, discard, and retrieval associated injury. Concern over ischemic organ injury underscores the reluctance to recover extrarenal DCD organs since lack of medical therapy to support inadequate allograft function limits their acceptability. Nevertheless, limited results with DCD pancreas, liver, and lung allografts (but not heart) are now approaching that of donors with brain death organs. Pretransplant machine perfusion of DCD kidneys (vs. static storage) may reduce delayed graft function but has no effect on long-term organ function and survival. Normothermic regional perfusion used during DCD abdominal organ retrieval may reduce ischemic organ injury and increase the number of usable organs, although critical confirmative studies have yet to be done. Minor increases in usable DCD kidneys could accrue from increased use of pediatric DCD kidneys and from selective use of DCD/ECD kidneys, whereas a modest increase could result through utilization of donors declared dead beyond 1 hr from withdrawal of life support therapy. A significant increase in transplantable kidneys could be achieved by extension of the concept of living kidney donation in relation to imminent death of potential DCD donors. Progress in research to identify, prevent, and repair DCD-associated organ retrieval injury should improve utilization of DCD organs. Recent results using ex situ pretransplant organ perfusion of DCD organs has been encouraging in this regard.

Medication Noncompliance and its Implications in Transplant Recipients

The transplant patient’s therapeutic regimen consists of a lifelong drug therapy, including immunosuppressive drugs, prophylactic antimicrobials and often medications for the treatment of hypertension, diabetes mellitus and other comorbid diseases. Regular clinic appointments are required to monitor for signs and symptoms of immunological injury, recurrent disease and adverse drug effects. Patients are instructed to avoid risk factors for cardiovascular disease and cancer (e.g. diet, exercise, sun protection and not smoking). Noncompliance with all aspects of this regimen is substantial. Medication noncompliance leads to an increased incidence of acute rejection, chronic rejection and graft loss. Undoubtedly, many practitioners fail to appreciate the extent of noncompliance as the signs are often subtle and most patients are unwilling to disclose deliberate or widespread disregard for medication use. Newer immunosuppressive agents, particularly once-daily medications and long-acting antibody preparations offer convenience and monitoring that may improve compliance. This review focuses on the prevalence, correlates and consequences of medication nonadherence after organ transplantation. Current recommendations to enhance adherence are discussed.

Management of Thrombophilia in Renal Transplant Patients

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation.

Donor-transmitted parvovirus infection in a kidney transplant recipient presenting as pancytopenia and allograft dysfunction

Abstract: Parvovirus B19 is a nonenveloped single‐stranded DNA virus that commonly causes a benign childhood infection typically manifesting as a ‘slapped‐cheek’ rash. In immunodeficient hosts, this infection can cause persistent anemia and occasionally pancytopenia. Recently, direct renal involvement has been reported in renal transplant recipients leading to various forms of glomerulopathy and allograft dysfunction. Most cases are primary infections and are donor transmitted through the transplanted organ. Clinical and virological response to intravenous immunoglobulin (Ig) is usually excellent.

Clinical results of an organ procurement organization effort to increase utilization of donors after cardiac death.

Background. To stimulate organ donation, an organ procurement organization (OPO)-wide effort was undertaken to increase donors after cardiac death (DCD) over a 5-year period. This included commonality of protocols, pulsatile perfusion of kidneys, centralization of data and a regional allocation variance designed to minimize cold ischemia times and encourage adoption of DCD protocols at transplant centers. Results. In one OPO, eight centers initiated DCD programs in 11 hospitals. A total of 52 DCD donors were procured, increasing from four in 1999 to 21 in 2003. Eleven donors had care withdrawn in the operating room, whereas 41 had care withdrawn in the ICU. In all, 91 patients received renal transplants from these 52 donors (12 kidneys discarded, one double transplant), whereas 5 patients received liver transplants. One-, two-, and three-year kidney graft survival rates were 90%, 90%, and 82%, respectively. Fifty-five percent of patients needed at least one session of hemodialysis postoperatively. Mean recipient hospital length of stay was 11.1±6 days. Mean creatinine levels at 3, 6, 12, and 24 months were 1.65, 1.40, 1.41, and 1.40, respectively. Conclusions. DCD donors can be an important source of donor organs and provide excellent overall outcomes. Regional cooperation and a prospectively considered allocation and distribution system are important considerations in stimulating DCD programs.

Good samaritan kidney donation

Because close genetic matching between the donor and recipient is no longer required to achieve a highly successful outcome, there is currently widespread acceptance of a kidney transplant from a live donor who is genetically unrelated, but emotionally connected to the recipient. This concept has recently been taken a step further to include kidney donation from strangers—individuals who are not genetically or emotionally tied to the recipient. The volunteer stranger donor may express a desire to donate to any person on the transplant waiting list, termed nondirected live-kidney donation. Alternatively, the volunteer may become aware of a specific individual with end-stage renal disease (ESRD), but have no connection or previous relationship with the patient, termed directed stranger donation. The term “good samaritan” may be applied to either case, because the volunteer helps a stranger in a profoundly charitable way. Herein, we describe the development and growth of a Good Samaritan Kidney Donor program at a single institution. A general acceptance of good samaritan donation at our center, favorable publicity, and a geographically defined population base all contributed to the success of this program.

Utility of a mathematical nomogram to predict delayed graft function : A single-center experience

Background. In 2003, Irish and colleagues published a weighted nomogram designed to predict the risk of delayed graft function (DGF) in a given transplant. It was anticipated that the predictive nomogram would permit preemptive therapies or allocation decisions based on the risk of DGF. The potential for reducing unfavorable outcomes and expenses appeared significant. This nomogram, however, was developed using population data found in the United States Renal Data System and has not been prospectively validated. Methods. We evaluated the accuracy and utility of this nomogram in all cadaver renal transplants performed at a single transplant center. In addition, we correlated DGF with a variety of independent donor and recipient variables outside the established nomogram. Results. The average nomogram DGF risk was 0.41 (a 41% chance of DGF) among the 169 cases in our population. The mean was 0.45±0.14 (confidence interval: 0.40–0.49) for the 42 DGF-positive subjects, and 0.40±0.14 (confidence interval: 0.38–0.43) for the 127 DGF-negatives (t=1.80; P=0.07). Conclusions. Although there was a trend showing the predictive value of the nomogram the overlap was tremendous, limiting the accuracy of the calculation for any single recipient. Prospective application of a nomogram on a case-by-case basis did not contribute meaningful information that could guide clinical decision-making regarding use, allocation or immunosuppressive regimen aimed at minimizing DGF.

Direct and Indirect Costs Following Living Kidney Donation: Findings From the KDOC Study.

Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to