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Kidney Transplantation

by Martin Hertl, MD, PhD, Paul S. Russell, MD

Kidney transplantation is the most common type of solid organ transplantation; the primary indication is end-stage renal failure. Absolute contraindications include comorbidities that could compromise graft survival (eg, severe heart disorders, cancer), which can be detected via thorough screening. Relative contraindications include poorly controlled diabetes, which can lead to renal failure, and certain viral infections (eg, hepatitis C with end-stage liver disease), which could be worsened by the immunosuppression required by transplantation. Patients in their 70s and sometimes 80s may be candidates for transplants if they are otherwise healthy and functionally independent with good social support, if they have a reasonably long life expectancy, and if transplantation is likely to substantially improve function and quality of life beyond simply freeing them from dialysis. Patients with type 1 diabetes may be candidates for simultaneous pancreas-kidney or pancreas-after-kidney transplantation.

More than one half of donated kidneys come from previously healthy, brain-dead people. About one third of these kidneys are marginal, with physiologic or procedure-related damage, but are used because demand is so great. More kidneys from non–heart-beating donors (called donation-after-cardiac-death [DCD] grafts) are being used. These kidneys may have been damaged by ischemia before the donor's death, and their function is often impaired because of acute tubular necrosis; however, over the long term, they seem to function as well as kidneys from donors that meet standard criteria (called standard criteria donors [SCD]). The remaining donated kidneys (about another 40%) come from living donors; because of limited supply, allografts from carefully selected living unrelated donors are being increasingly used. Living donors relinquish reserve renal capacity, may put themselves at risk of procedural and long-term morbidity, and may have psychologic conflicts about donation; therefore, they are evaluated for normal bilateral renal function, absence of systemic disease, histocompatibility, emotional stability, and ability to give informed consent. Hypertension, diabetes, and cancer (except possibly CNS tumors) in prospective living donors usually preclude kidney donation.

Use of kidneys from unrelated living donors has been increasing; kidney exchange programs often match a prospective donor and recipient who are incompatible with other similar incompatible pairs. When many such pairs are identified, chain exchanges are possible, greatly increasing the potential for a good match between recipient and donor.

If ABO matching is not feasible, sometimes ABO-incompatible transplantation can be done; with careful selection of donors and recipients and with pretransplant treatment (plasma exchange and/or IV immunoglobulins [IVIG]), outcomes can be comparable to those of ABO-compatible transplantation.

Procedure

The donor kidney is removed during a laparoscopic (or rarely, an open) procedure, perfused with cooling solutions containing relatively large concentrations of poorly permeating substances (eg, mannitol, hetastarch) and electrolyte concentrations approximating intracellular levels, then stored in an iced solution. Kidneys preserved this way usually function well if transplanted within 24 h. Although not commonly used, continuous pulsatile hypothermic perfusion with an oxygenated, plasma-based perfusate can extend ex vivo viability up to 48 h.

Dialysis may be required before transplantation to ensure a relatively normal metabolic state, but living-donor allografts appear to survive slightly better in recipients who have not begun long-term dialysis before transplantation. Recipient nephrectomy is usually not required unless native kidneys are infected. Whether transfusions are useful for anemic patients anticipating an allograft is unclear; transfusions can sensitize patients to alloantigens, but allografts may survive better in recipients who receive transfusions but do not become sensitized, possibly because transfusions induce some form of tolerance.

The transplanted kidney is usually placed in the iliac fossa. Renal vessels are anastomosed to the iliac vessels, and the donor ureter is implanted into the bladder or anastomosed to the recipient ureter. Vesicoureteral reflux occurs in about 30% of recipients, but usually without adverse effects.

Immunosuppressive regimens vary. Commonly, calcineurin inhibitors are begun immediately after transplantation in doses titrated to minimize toxicity and rejection while maintaining trough blood levels high enough to prevent rejection. On the day of transplantation, IV or oral corticosteroids are also given; dose is tapered over the following 12 wk.

Complications

Despite use of immunosuppressants, about 20% of recipients have one or more rejection episodes within the first year after transplantation. Most episodes are easily treated with a corticosteroid bolus; however, they contribute to long-term insufficiency, graft failure, or both. Signs of rejection vary by type (see Manifestations of Transplant Rejection by Category).

Rejection can be diagnosed by percutaneous needle biopsy if the diagnosis is unclear clinically. Biopsy may also help distinguish antibody-mediated from T-cell–mediated rejection and identify other common causes of graft insufficiency or failure (eg, calcineurin inhibitor toxicity, diabetic or hypertensive nephropathy, polyomavirus type 1 infection). Advanced tests that may improve accuracy of rejection diagnosis include measurement of urinary mRNA-encoding mediators of rejection and gene expression profiling of biopsy samples using DNA microarrays.

Chronic allograft nephropathy refers to graft insufficiency or failure 3 mo after transplantation. Most cases are attributable to one or more of the above causes. Some experts believe the term should be reserved to describe graft insufficiency or failure when biopsy shows chronic interstitial fibrosis and tubular atrophy not attributable to any other cause.

Intensified immunosuppressive therapy (eg, with high-dose pulse corticosteroids or antilymphocyte globulin) usually reverses accelerated or acute rejection. If immunosuppressants are ineffective, dose is tapered and hemodialysis is resumed until a subsequent transplant is available. Nephrectomy of the transplanted kidney is necessary if hematuria, graft tenderness, or fever develops after immunosuppressants are stopped.

Prognosis

Most rejection episodes and other complications occur within 3 to 4 mo after transplantation; most patients then return to more normal health and activity but must take maintenance doses of immunosuppressants indefinitely.

At 1 yr, survival rates are

  • Living-donor grafts: 98% (patients) and 94% (grafts)

  • Deceased-donor grafts: 94% (patients) and 88% (grafts)

Subsequent annual graft loss rates are 3 to 5% with a living-donor graft and 5 to 8% with a deceased-donor graft.

Among patients whose graft survives the first year, half die of other causes with the graft functioning normally; half develop chronic allograft nephropathy with the graft malfunctioning in 1 to 5 yr. Rates of late failure are higher for blacks than for whites.

Doppler ultrasonographic measurement of peak systolic and minimal end-diastolic flow in renal segmental arteries 3 mo after transplantation may help assess prognosis, but the best clinical predictor remains serial determination of serum creatinine. In a specific patient, the most recently obtained creatinine levels should be compared with previous levels; a sudden increase in creatinine indicates the need to consider rejection or another problem (eg, vascular compromise, obstruction of the ureter). Ideally, serum creatinine should be normal in all posttransplant patients 4 to 6 wk after kidney transplantation.

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