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Renal transplantation 

Renal transplantation

Chapter:
Renal transplantation
Author(s):

P. Sweny

DOI:
10.1093/med/9780199204854.003.210703_update_001

Update:

Renal transplant statistics have been updated. Discussion of extended criteria donors, dual kidney transplants and increasing prevalence of living donation. Data on renal transplantation in HIV-positive recipients.

Updated on 25 May 2011. The previous version of this content can be found here.
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date: 28 April 2017

Renal transplantation is the preferred option for the treatment of endstage chronic renal failure in patients for whom there are no major medical contraindications. In well-selected recipients, both life expectancy and quality of life are superior to treatment with long-term dialysis. However, as the dialysis population continues to grow, the gap between supply and demand for renal transplantation is widening. Attempts to bridge this gap have included (1) relaxation of the criteria for a suitable deceased donor (expanded/extended criteria or ‘marginal donors’); (2) reversion to the procurement of kidneys from donors with cardiac death (DCD donors, previously known as non-heart beating donors); and (3) encouragement of living donation—including techniques for desensitization of recipients, also paired exchanges, both to circumvent blood group incompatibilities or preformed antibodies that would otherwise bar transplantation.

Technical aspects

Surgery—the new kidney is placed in one or other iliac fossa, usually in an extraperitoneal position that allows ease of repeated biopsy to detect cause of graft dysfunction. Typically, the renal artery is anastomosed end to side to the common iliac artery or end to end to the internal iliac artery, the renal vein to the common iliac vein, and the transplant ureter is implanted into the bladder through a submucosal tunnel. The native kidneys are left in situ unless there are particular reasons for them to be removed in a separate pretransplant operation.

Immunosuppression—excepting for transplants between HLA-identical twins, immunosuppression is required to prevent rejection, but there is no clear consensus on the best immunosuppressive regimen. Most centres use an induction antibody directed against CD25 (the IL-2 receptor), followed by what is now called standard triple therapy—comprising a calcineurin inhibitor (CNI) (ciclosporin or tacrolimus), combined with either mycophenolate mofetil or azathioprine, and steroids. Steroids are not infrequently tailed off rapidly in the early post-transplant period.

Transplant rejection

This can be classified into four main categories: (1) hyperacute—due to preformed cytotoxic antibodies, always leads to very rapid graft failure; (2) accelerated—a predominantly T-cell-mediated rejection crisis occurring within the first few days, cannot usually be treated satisfactorily; (3) acute cellular—due to a primary cell-mediated response, occurs in 10% to 20% of recipients, manifests histologically as tubulitis, first-line treatment (usually successful) with intravenous steroids; (4) humoral—antibody-mediated, manifest histologically as marked staining for the complement breakdown product C4d in peritubular capillaries, best treatment uncertain.

Complications of renal transplantation

Specific side effects of immunosuppressive agents—these are important causes of morbidity and (rarely) mortality, with steroids culpable for many of the complications of transplantation, and nephrotoxicity being the main drawback of CNIs. The desire to overcome these problems is one of the main drivers in the search for new immunosuppressants and immunosuppressive regimens.

Nonspecific side effects of immunosuppressive agents—all currently available immunosuppressive regimen are nonspecific in the sense that they suppress not only the immune response to the allograft, but also the immune response to infections and tumours.

Infective complications—transplant recipients are vulnerable to opportunistic infections including (1) viral infections—particularly cytomegalovirus (the main infectious complication in solid organ transplantation, with manifestation ranging from asymptomatic viraemia to life-threatening multiorgan failure), Epstein–Barr virus (EBV or HHV4), varicella zoster virus, herpes simplex, human polyomavirus (especially BK, which can lead to nephropathy and graft failure), human papillomavirus (HPV), and HIV; (2) bacterial infections—particularly mycobacterial, nocardia, nontyphoid salmonella, listeria; (3) fungal infections—including candidiasis and aspergillosis aspergillus and pneumocystis (a dreaded complication of transplantation before routine introduction of prophylaxis with co-trioazole or pentamidine); (4) parasitic infections—including Strongyloides stercoralis, scabies, and toxoplasmosis.

Malignant complications—post-transplant neoplasia is an important cause of morbidity and mortality. Particular conditions include (1) post-transplant lymphoproliferative disorder (PTLD)—driven by EBV, first-line treatment by stepwise reduction in immunosuppression; (2) Kaposi’s sarcoma—caused by HHV8, first-line treatment by switch of immunosuppression to sirolimus; (3) HPV—responsible for skin, vulval, and anogenital warts, and some types are associated with carcinoma. After 20 years, most renal transplant recipients who are white will have cutaneous squamous cell carcinoma.

Other complications—these include hypertension, accelerated atherosclerosis, electrolyte, musculoskeletal, haematological, gastrointestinal, and cosmetic disorders.

Prognosis

The short-term outcome of renal transplantation has improved markedly over the last 30 years, with 1-year graft survival around 90%. However, the rate of chronic graft-loss remains at about 4% per year, with the descriptive term ‘chronic allograft nephropathy’ commonly (but unhelpfully, because it does not imply a mechanism or aid management) being applied to the failing graft. The commonest cause of insidious late graft failure is probably calcineurin toxicity, which by 10 years probably affects nearly all exposed grafts to some degree. Conversion from CNIs to either mycophenolate mofetil or sirolimus can prolong graft survival, and is being used increasingly in many centres.

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