INSTRUCTION

Examine this patient's abdomen.

SALIENT FEATURES

History

· History of chronic renal failure - determine duration, aetiology (diabetes, hyper-tension, glomerulonephritis).

· History of haemodialysis.

· History of arteriovenous fistula.

· History of transplanted kidney.

Examination

· Laparotomy scar (comment on the scar).

· Arteriovenous fistulas in arms.

· Transplanted kidney felt in either right or left iliac fossa.

Proceed as follows:

· Tell the examiner that you would like to look for other signs of uraemia (see pp 585-8).

· Do know the differential diagnosis for masses in the right/left iliac fossa (see p. 331).

DIAGNOSIS

This patient has a transplanted kidney (lesion) probably due to diabetic nephropathy as evidenced by the sugar-free drinks by the

bedside (aetiology).

QUESTIONS

Mention a few indications for renal transplantation.

End-stage renal diseases; the most common diseases that result in referral of patients for transplantation include:

· Diabetes mellitus with renal failure.

· Hypertensive renal disease.

· Glomerulonephritis.

ADVANCED-LEVEL QUESTIONS

Would you refer a patient for renal transplantation before instituting haemodialysis?

Referral for renal transplantation need not be delayed until the patient has begun dialysis. It is acceptable and, in fact, usually

preferable to refer the patient to a renal transplant unit before dialysis is required. With judicious planning on the part of the general

practitioner, renal physician and transplant surgical team, transplantation can be performed before dialysis is even required.

In which age group is transplantation preferred to dialysis?

Infants and children have a high morbidity rate on long-term haemodialysis or peritoneal dialysis. Thus, renal transplantation from

parents or siblings improves growth and allows a more normal lifestyle.

Is there any advantage to HLA matching before transplantation?

Kidneys from living related donors who are HLA identical and also red blood cell ABe matched have a 90% survival rate at 1 year;

less well matched grafts tend to have a somewhat lower survival rate. Kidney transplants from matched cadaver donors survive

nearly as long, especially if the recipient does not contain antibodies to donor antigens.

There is some evidence that HLA mismatching has a greater effect on living related than it does on cadaveric donor kidney

transplantation. Recent evidence has shown that HLA-matched kidneys, particularly for DR, B and A antigens, are associated with

long-term survival of the patient. Complete matching of DR, B and A loci is associated with the best chance of success. HLA-DR

matching appears to have the greatest impact on survival, followed by B, and lastly the A loci (N Engl J Med 1994; 331: 803-5).

Should repeated blood transfusions be avoided in a patient waiting for a renal transplant?

If the anaemia is well tolerated and is due to the renal failure per se, blood trans-fusion should be avoided as it carries a risk of HLA

sensitization. Pretreatment of recipients with multiple blood transfusions from the donor tends to increase graft survival, in contrast

to the deleterious effect on bone marrow engraftment.

What other factors are known to cause sensitization to HLA antigens?

Pregnancy, previously failed transplant.

What drugs are used for post-transplant immunosuppression?

Steroids, azathioprine and ciclosporin used independently or in combination. Newer drugs include FK 506, rapamycin, sirolimus,

mycophenolate mofetil, and daclizumab.

What are the contraindications for kidney transplantation ?

· A positive cross-match by cytotoxicity testing between recipient serum and donor cells is considered to be a contraindication for

transplantation.

· Presence of HIV or other infectious agents on donor screening.

What are the complications of renal transplantation?

· Opportunistic infection, e.g. cytomegalovirus, Pneumocystis.

· Premature coronary artery disease.

· Hypertension primarily to ciclosporin.

· Lymphomas and skin cancers.

· De novo glomerulonephritis in the transplanted kidney.

· Complications of steroid therapy, e.g. aseptic necrosis of bone.

What do you know about warm ischaemic time?

Shorter warm ischaemic time of the transplanted kidney is associated with longer survival of the recipient. However, a slight increase

in the duration of cold ischaemia justifies HLA-matching before kidney transplantation because of higher rates of survival, a lower

incidence of the episodes of rejection and lower risk of loss as a result of rejection (N Engl J Med 2000; 343:1078 84).

What is the survival rate following kidney transplant?

The 2-year kidney graft survival rate for living related donor transplantation is 85%, whereas in cadaveric donor transplantation it is

about 70%.

What do you know about rejection of the transplanted kidney?

It may be acute or chronic and must be suspected when the graft is tender, the urine output is falling or the creatinine concentration

is rising. It is a complex process in which both cell-mediated immunity and circulating antibodies play a role. Evaluation of suspected

rejection usually requires graft biopsy.

· Acute rejection is characterized by a lymphocytic interstitial infiltrate with destruction of epithelial cells. It usually responds to

treatment which includes high-dose methyl prednisolone, antilymphocytic globulin and anti-T-lymphocyte monoclonal antibody

(OKT3) administration.

· Chronic rejection shows histological features of interstitial fibrosis, atrophy of tubules and proliferation of the arterial intima.

There is no specific treatment and general management of chronic renal failure should be reinstituted.

Is there any advantage of renal transplantation as compared to long-term dialysis in end-stage renal disease?

The benefits of renal transplantation include better quality of life (Am J Kid Dis l990 15 901-8), reduced medical expenses (semi,

Ncphro[ 1999; 12. 98d-9) and about a 68% reduction in the long-term risk of death (N Engl J Med 1999; 341: 1725-30).

What is the role of pancreas-kidney transplantation in patients with diabetes mellitus and end-stage renal

failure?

Pancreas transplantation in type I diabetes can reverse the lesions of diabetic nephropathy but reversal requires

more than 5 years of normoglycaemia (N Engl J Med 1998; 339: 69-75). Simultaneous pancreas-kidney

transplantation prolongs survival in patients with diabetes and end-stage renal failure (Lancet1999; 353: 1915-19).

Does acute myocardial infarction influence long-term survival among patients on long-term dialysis?

Patients on dialysis who have an acute myocardial infarction have high mortality from cardiac causes and poor

long-term survival (N Engl J Med 1998: 339: 799-8O5).

In the 1920s, Alexis Carrel developed the technique of vascular anastomoses which made possible David Hume's and Joseph Murray's human

allograft attempts in the early 1950s.

Joseph E. Murray (1919-), Professor of Surgery, Brigham and Women's Hospital and Harvard Medical School, was awarded the 1990 Nobel Prize for

Medicine for his pioneering work on organ transplantation along with Thomas E. Donnall (1920-) of the Fred Hutchinson Cancer Research Centre,

Seattle, Washington, USA (Murray JE, et al. Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. N Engl J Med 1963;

268:1315-23).

In 1966, Terasaki and co-workers reported the association between HLA matching and outcome in patients receiving cadaveric organs (Ann N YAcad

Sci 1966; 129: 500-20).

The observation by Schwartz and Damasheck that 6-mercaptopurine was effective in blocking primary but not secondary antibody response in rabbits

paved the way for drug-induced immunosuppression in the late 1950s (Nature 1959; 183: 1682-3).