Transplantation.

Transplantation represents the best therapy for non-recoverable organ failure. Transplantation is divided into two major categories: solid organ transplants (kidney, heart, pancreas, lung, liver, small bowel, and more recently even the face and upper limbs) and tissue transplants (corneas, blood, bone, skin and stem cells). Tissue may be procured several hours after cardiac death.

Donation

With modern immunosuppression, solid organ transplantation is the ideal management for all end-organ failure. The demand for solid organs of all types has risen exponentially, while the number of organ donors remains almost static. Consequently, live donor organ donation has increased to cope with demands. In Europe and the USA more than 50% of kidney donors are living relatives or friends of the patient. Risks of live donation vary considerably with regard to the organ being donated, i.e. kidney--minimal; pancreas, lung and liver--more substantial. (1) A living donor kidney has a 20% better graft survival at 5 years than a deceased donor kidney. Every medical practitioner should be familiar with criteria for establishing brain death. (2)

Kidney transplantation

Patient survival is significantly increased compared with dialysis. (3) Currently, immunosuppressant therapy has improved to enable long-term graft survival. Overall 50% of kidneys transplanted can be expected to be functional 10 years later. Steroid-free immunosuppression and graft tolerance are current fields of development. Waiting lists are long and allocation systems for fair distribution are used in line with Chapter 5 of the National Health Act, 2003. Regulations regarding the general control of human bodies, tissues and organs state that: 'Allocation must be based purely on clinical needs which may not include race, religious belief, financial and political affiliation.'

Pancreas transplantation

Whole-organ pancreas transplantation is performed in three ways:

* Simultaneous pancreas/ kidney transplantation (SPK)--type 1 diabetic with end-stage renal disease is given the pancreas and kidney from the same donor--80% of patients remain off dialysis and insulin free at 5 years post transplantation. (4) Recurrent diabetic nephropathy is prevented and secondary effects of diabetes do not progress.

* Pancreas transplantation after kidney transplantation (PAK)--used in patients where a living donor kidney is available. A cadaver pancreas is transplanted later.

* Pancreas transplantation alone. This requires the trading of insulin therapy for immunosuppression. As a rule this is not a good trade unless the type 1 diabetes results in life-threatening hypoglycaemic events or is uncontrollable with conventional therapy.

Islet transplantation

A whole donor pancreas is processed to isolate islet cells, which are then cultured, placed in suspension and injected percutaneously into the portal vein. Two or three such transplants may be required to obtain the end result of insulin freedom. Shapiro et al. (5) removed steroids from the immunosuppressive drug regimen of islet transplant patients and improved 1-year insulin freedom to 80%. An explosion of islet cell transplant units occurred worldwide. (5) Unfortunately only 10% of patients remain insulin free at 5 years.

Liver transplantation

This is the ideal therapy for end-stage liver disease and fulminant liver failure. Outcomes are excellent, with 90% 1-year survival and 75% 5-year survival. Liver transplantation is no longer an extremely risky venture, but rather routine, therapy. Indications are deterioration of liver function as gauged by MELD (model for end-stage liver disease). (6) Other indications in patients with liver disease are severe lethargy, variceal bleeding with diminished liver reserve, urticaria, ascites, encephalopathy or spontaneous bacterial peritonitis. (7)

Small-bowel transplantation

This is a highly specialised field applied mostly to infants. Better results are increasingly being obtained. Donors are frequently neonates who are brain dead as a result of a frustrated parent shaking the child violently--the 'shaken baby syndrome'. (8)

Heart transplantation

This is undertaken primarily to improve survival rates and secondarily to improve quality of life. An 80% 3-year survival is expected. Outcomes are determined by both recipient and donor factors. (9)

Lung transplantation

Survival is best with bilateral lung transplant, then single lung transplant, and lastly combined heart-lung transplant. A significant survival advantage exists, and quality of life is returned to near normal in most patients. (10)

Stem cells

Stem cell storage from umbilical cord blood is available but expensive. Currently, applicable uses are limited. Experimentation with cardiac muscle Regeneration (11) and neurological spinal cord regeneration are exciting fields with enormous potential.

References

(1.) Grewal HP, Thistlewaite JR, jun, Loss GE, et al. Complications in 100 living-liver donors. Ann Surg 1998; 228: 214.

(2.) The Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults (summary statement). Neurology 1995; 45: 1012.

(3.) Port FK, Wolfe RA, Mauger EA, et al. Comparison of survival probabilities for dialysis patients versus cadaveric renal transplant recipients. JAMA 1993; 270: 1339.

(4.) Sutherland D, Gruessner A, Moudry-Munns K. International Pancreas Transplant Registry report. Transplant Proc 1994; 26: 407.

(5.) Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med 2006; 355: 1318.

(6.) Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 2003; 124: 91.

(7.) Steinman T, Becker B, Frost A, et al. Guidelines for the Referral and Management of Patients Eligible for Solid Organ Transplantation. Transplantation 2001; 71: 1189.

(8.) Richards PG, Bertocci GE, Bonshek RE, et al. Shaken baby syndrome. Arch Dis Child 2006; 91: 205.

(9.) Taylor DO, Edwards LB, Boucek MM, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult heart transplant report--2005. J Heart Lung Transplant 2005; 24: 945.

(10.) Smeritschnig B, Jaksch P, Kocher A, et al. Quality of life after lung transplantation: a cross-sectional study. J Heart Lung Transplant 2005; 24: 474.

(11.) Lee MS, Makkar RR. Stem-cell transplantation in myocardial infarction: a status report. Ann Intern Med 2004; 140: 729.

R BRITZ, MB BCh, DA (SA), FCS (SA)

Vascular Surgeon and Chief, Transplantation, University of the Witwatersrand and Johannesburg Hospital