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Antilymphocyte Globulin, Monoclonal Antibodies, and Fusion Proteins

Renal transplantation is the preferred treatment for most end-stage renal diseases. Transplantation’s success, however, has been counterbalanced, by its dependence on immunosuppressive drugs with their related infectious, metabolic, and malignant complications. Consequently, a common goal throughout the history of clinical transplantation has been the minimization and individualization of immunosuppressive therapy. Typically, drugs with highly specific mechanisms of action have been preferred over drugs with broad effects,…

mTOR Inhibitors: Sirolimus and Everolimus

Sirolimus and its closely related analog everolimus are potent immunosuppressive agents that impair lymphocyte activation and proliferation by inhibiting the mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin. The mTOR inhibitors emerged in the 1990s as a new class of immunosuppressive agent and a promising alternative to calcineurin inhibitor (CNI)-based therapy in organ transplantation, particularly because mTOR inhibitors were not believed…

Calcineurin Inhibitors

Although the improved outcomes over the past 60+ years in kidney transplantation have been related to a number of factors, the effect of immunosuppression has perhaps been the most significant. The advent of the calcineurin inhibitors (CNIs), first cyclosporine and then tacrolimus, represented a huge advance for the field of transplantation in general and for kidney transplantation in particular. It is fair to describe transplant outcomes…

Steroids

Introduction When the first renal transplants were being performed in the early 1960s the immunosuppressive properties of corticosteroids were already noted, and steroids were successfully used to reverse episodes of acute rejection. In his 1964 book, Starzl described the use of steroids as a “pretreatment” alongside azathioprine as prophylaxis against rejection, based on the premise that rejection was almost inevitable with azathioprine alone. This work was…

Azathioprine and Mycophenolates

Introduction Whereas calcineurin inhibitors (cyclosporine and tacrolimus) block early signaling events and cytokine production, both azathioprine and mycophenolates, often termed antiproliferatives, exert effects downstream in the cell cycle, interfering with cytokine-dependent signals and lymphocyte proliferation. Azathioprine, usually in combination with corticosteroids, was the backbone of immunosuppression in renal transplantation from the early 1960s to the early 1980s, after which cyclosporine (CsA) was added to the mix.…

Early Course of the Patient With a Kidney Transplant

A successful long-term outcome for a new kidney transplant recipient depends on the early perioperative management and course after surgery. Important factors affecting long-term outcome include the occurrence of delayed graft function (DGF); episodes of acute rejection; early surgical complications, such as urinary obstruction, urine leak, or vascular complications; and sepsis. Toxicity from calcineurin inhibitors (CNIs) can lead to chronic transplant damage later in the posttransplantation…

Perioperative Care of Patients Undergoing Kidney Transplantation

The first description of anesthesia for kidney transplantation (KTx) appeared in the early 1960s. It details the pioneering efforts in Boston with living related KTx between identical twins. The only monitors used in the 17 initial recipient cases described were a blood pressure cuff and an electrocardiogram (ECG). All recipients received neuraxial anesthesia. Within a few years, general anesthesia had become the norm and the first…

Transplantation and the Abnormal Bladder

The ability of the urinary bladder to store urine at low pressure and to empty completely at intervals with simultaneous relaxation of the sphincter complex is essential to preserve the integrity of the kidneys and to achieve continence. Although an abnormal lower urinary tract is not a contraindication to renal transplantation, lower urinary tract dysfunction (LUTD) needs to be addressed before and after transplantation. In this…

Surgical Techniques of Kidney Transplantation

Kidney transplantation is a major surgical procedure that involves both vascular and ureteric anastomoses, and it is usually performed by a dedicated transplant surgeon, although in the past it was performed predominantly by urologists or vascular surgeons. Most recipients are already established on dialysis, although some may avoid dialysis by having the transplant preemptively, and many consider this the gold standard treatment. Preemptive transplantation confers a…

Histocompatibility in Renal Transplantation

Historical Background The study of histocompatibility accelerated during the 1960s when the pioneers of clinical kidney transplantation recognized that graft destruction was mediated through immunologic mechanisms. In 1961 the introduction of chemical immunosuppression, first 6-mercaptopurine followed soon after by azathioprine and steroids, enabled short and medium-term success. However, 40% to 50% of deceased donor transplants were lost because of immediate or early graft failure due to…

Kidney Preservation

Introduction At the start of the first transplant programs, the donor and recipient would be operated in the same surgical center. The only preservation method therefore undertaken would be to flush out the kidney with either blood or Ringer’s lactate and to use surface cooling with ice water, because hypothermia was supposed to be protective by reducing metabolism. Very early transplant work in twins and animal…

Donor Nephrectomy

Deceased Donor Nephrectomy Deceased donor renal donation predominates as the source of transplantable kidneys. In the US, deceased donors provide approximately 13,000 kidneys per year or 70% of the available pool of transplantable kidneys ( Fig. 8.1 ). Recent years have seen an increase in the number of deceased donors secondary to the opioid crisis in North American (and Europe) and the resultant number of referrals…

Medical Evaluation of the Living Donor

History of Living Donation and Donor-Related Ethics The first long-term successful organ transplant was a living donor kidney transplant between monozygotic twin brothers performed in 1954 at the Peter Bent Brigham Hospital in Boston. This procedure marked the first time in history that a healthy person underwent a major surgical procedure that they did not need, solely for the benefit of another person, and this reality…

Brain Death and Cardiac Death: Donor Criteria and Care of Deceased Donor

Introduction As the number of people awaiting organ transplantation grows yearly, the relative scarcity of available organs increasingly requires a standardized, evidence-based approach to the management of each donor. From the initial diagnosis of death by neurologic criteria or imminent death from cardiorespiratory failure to the optimization of donor physiology before removal of organs, the intensivist plays an integral role in this first portion of the…

Access for Renal Replacement Therapy

Introduction Worldwide the population of patients with chronic kidney disease (CKD) is expanding, leading to increasing numbers of patients hitting end-stage renal failure (ESRF) and requiring renal replacement therapy (RRT). In the UK the incidence of new dialysis starters increased from 115 per million population (pmp) in 2014 to 120 pmp in 2015, resulting in 7814 new patients initiating RRT. The median age of these new…

The Recipient of a Renal Transplant

The Patient with Chronic Kidney Disease The insidious nature of progressive uremia deludes many patients with chronic kidney disease (CKD) into failing to take the opportunity to understand their disease; learn about their dialysis, transplant, and palliative care options; and plan their future. Relatively asymptomatic decline in renal function may explain why many ignore the early warnings of disease and fail to optimize their medical care…

Chronic Kidney Failure: Renal Replacement Therapy

Introduction Renal replacement therapy (RRT) is a general term encompassing a range of different treatment modalities for patients with what was formally termed acute renal failure and end-stage kidney disease, which are now called acute kidney injury stage 3 (AKI-3) and chronic kidney disease stage 5 dialysis (CKD5d), respectively ( Table 3.1A and B ). RRT includes various forms of dialysis (hemodialysis, hemodiafiltration, and peritoneal dialysis),…

The Immunology of Transplantation

Introduction Solid organ transplant requires the removal of an organ from one individual, the donor, and its placement in the recipient. Whether the donor is living or deceased, this process inevitably requires a temporary cessation of circulation and hence oxygenation, with attendant cellular dysfunction and damage. Thus when the blood supply is restored to the allograft in the recipient, and the recipient’s immune system can access…

Kidney Transplantation: A History

The modern period of transplantation began in the late 1950s, but two earlier periods of interest in clinical and experimental transplantation were the early 1950s and the first two decades of the 20th century. Hamilton provides a bibliography of the history of organ transplantation. Table 1.1 summarizes landmarks in kidney transplantation. Table 1.1 Landmarks in Kidney Transplantation 1902 First successful experimental kidney transplant 1906 First human…

Osteochondral Autograft Transplantation

Introduction The treatment of symptomatic focal articular cartilage defects continues to present a clinical dilemma for many orthopedists. Surgical approaches to this problem can be categorized into those that attempt to resurface focal defects through tissue repair or regeneration and those that reconstitute articular cartilage surfaces through transplantation of intact osteochondral grafts. The former includes repair strategies, such as marrow stimulation, and cell-based therapies, such as…