Defining the roles and responsibilities of the kidney transplant medical director: A necessary step for future training, mentoring, and professional development.

The management of a kidney transplant program has evolved significantly in the last decades to become a highly specialized, multidisciplinary standard of care for end-stage kidney disease. Transplant center job descriptions have similarly morphed with increasing responsibilities to address a more complex patient mix, increasing medical and surgical therapeutic options, and increasing regulatory burden in the face of an ever-increasing organ shortage. Within this evolution, the role of the Kidney Transplant Medical Director (KTMD) has expanded beyond the basic requirements described in the United Network for Organ Sharing bylaws. Without a clear job description, transplant nephrology trainees may be inadequately trained and practicing transplant nephrologists may face opaque expectations for the roles and responsibilities of Medical Director. To address this gap and clarify the key areas in which the KTMD interfaces with the kidney transplant program, American Society of Transplantation (AST) formed a Task Force of 14 AST KTMDs to review and define the role of the KTMD in key aspects of administrative, regulatory, budgetary, and educational oversight of a kidney transplant program.

The scope of coronary heart disease in patients with chronic kidney disease.

Chronic kidney disease (CKD) affects approximately 13% of the U.S. population and is associated with increased risk of cardiovascular complications. Once renal replacement therapy became available, it became apparent that the mode of death of patients with advanced CKD was more likely than not related to cardiovascular compromise. Further observation revealed that such compromise was related to myocardial disease (related to hypertension, stiff vessels, coronary heart disease, or uremic toxins). Early on, the excess of cardiovascular events was attributed to accelerated atherosclerosis, inadequate control of blood pressure, lipids, or inflammatory cytokines, or perhaps poor glycemia control. In more recent times, outcome research has given us further information that relates even lesser degrees of renal compromise to an excess of cardiovascular events in the general population and in those with already present atherosclerotic disease. As renal function deteriorates, certain physiologic changes occur (perhaps due to hemodynamic, inflammatory, or metabolic changes) that decrease oxygen-carrying capacity of the blood by virtue of anemia, make blood vessels stiffer by altering collagen or through medial calcinosis, raise the blood pressure, increase shearing stresses, or alter the constituents of atherosclerotic plaque or the balance of thrombogenesis and thrombolysis. At further levels of renal dysfunction, tangible metabolic perturbations are recognized as requiring specific therapy to reduce complications (such as for anemia and hyperparathyroidism), although outcome research to support some of our current guidelines is sorely lacking. Understanding the process by which renal dysfunction alters the prognosis of cardiac disease might lead to further methods of treatment. This review will outline the relationship of CKD to coronary heart disease with respect to the current understanding of the traditional and nontraditional risk factors, the role of various imaging modalities, and the impact of coronary revascularization on outcome.

Cardiovascular complications of immunosuppressive agents in renal transplant recipients.

Fatal and nonfatal cardiovascular events are the most important cause of graft loss in patients with a functioning graft following transplantation. The available data indicate that transplant patients have a high prevalence of hypertension, hyperlipidaemia and new onset diabetes mellitus after transplantation. The aetiology and pathogenesis of post-transplant hypertension, hyperlipidaemia and diabetes are multifactorial. In addition, disease of the native kidney and recurrence of renal disease can contribute to the development of cardiovascular disease in transplant recipients. Most transplant patients are at risk of clinically important drug-drug interactions involving immunosuppressive agents. Adverse reactions and drug-drug interactions should not be neglected when selecting an agent for treatment of cardiovascular risk factors in transplant recipients.

Association of CD20+ infiltrates with poorer clinical outcomes in acute cellular rejection of renal allografts.

We undertook a study to ascertain the relationship between the presence of CD20-positive B-lymphocytes in renal allografts undergoing acute cellular rejection and graft survival. We identified 27 patients transplanted between January 1, 1998 and December 31, 2001, with biopsy-proven Banff 1-A or Banff 1-B rejection in the first year after transplantation, and stained the specimens for CD20 and C4d. At least 4 years of follow-up data were available for each patient studied. Six patients had CD20-positive B-cell clusters in the interstitium, and 21 patients were negative for CD20 infiltrates. The CD20-positive group was significantly more likely to have steroid-resistant rejection and reduced graft survival compared to CD20-negative controls. This study supports prospective identification of CD20-positive B-cell clusters in biopsy-proven rejection and offers a therapeutic rationale for a trial of monoclonal anti-CD20 antibody in such patients.

Factors associated with improvement in deceased donor renal allograft function in the 1990s.

The decade of the 1990s saw an improvement in cadaveric renal graft function and dramatic reduction in the acute rejection (AR) rate. The purpose of this study was to determine whether the reduction in rejection rate was the primary cause of the improvement in graft function seen and whether this improved long-term graft survival. All adult patients who received a cadaver renal transplant between 1991 and 2000 and had graft survival of at least 6 mo and complete data for creatinine at 6 mo, HLA mismatch, delayed graft function, and acute rejection (AR) were identified in the United Network for Organ Sharing database. A total of 40,164 cases that met the inclusion criteria were identified. The mean Modification of Diet in Renal Disease GFR at 6 mo improved from 49.94 ml/min per 1.73 m2 in 1991 to 54.59 ml/min per 1.73 m2 in 2000 (P < 0.001). The improvement in GFR was not gradual but occurred over a 4-yr period between 1994 and 1997, coinciding with the introduction of new immunosuppressive agents mycophenolate mofetil and tacrolimus into maintenance immunosuppression regimens. The improvement was seen in all subgroups of patients, even patients without clinical AR or delayed graft function. The magnitude of improvement in patients without clinical AR was similar to that seen in patients with AR. The drop in clinical AR rate accounted for a minority of the improvement in graft function in the 1990s. Other factors, such as reduced drug toxicity and improved control of subclinical rejection, seem to account for the majority of the improvement. This improvement in graft function at 6 mo did not translate into improved long-term graft survival, however.

Effect of donor recipient age match on survival after first deceased donor renal transplantation.

Donor-recipient age matching has been proposed as a means of improving overall outcomes in deceased donor renal transplantation. It was hypothesized that donor-recipient age matching would improve patient survival time in younger recipients while not adversely affecting patient survivals in older recipients because they seldom outlive their grafts. By use of data from United Network of Organ Sharing Standard Transplant and Analysis and Research Files 50,320 patients were identified who underwent a first deceased donor renal transplantation between January 1, 1990, and December 31, 1997. Adjusted patient survival and death-with-graft function patient survival were analyzed from the date of transplantation. Patient survival was affected by donor age for all recipient age groups, including recipients older than 55 yr. The effect of donor age on patient survival is greater than that seen with HLA matching. The effect of donor age on patient survival persisted even when censoring recipients in whom grafts failed before death, suggesting that both longevity and quality of graft function are important in patient survival. Donor-recipient age matching is occurring to a limited degree in this population. Donor-recipient age matching would improve survival in younger recipients but would adversely affect survival in older patients by reducing the availability of younger donor kidneys for this group. The issue of donor-recipient age matching needs to be debated among the public and transplantation community so that a logical and just system can be developed.