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Sunday, September 13, 2009

Kidney Transplantation: Treatment Options of End Stage Renal Disease

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Living transplantation
     • First successful kidney transplantation between twin brothers in Boston on December 23, 1954
     • Human beings can live well with only one kidney
     • Many Benefits; better survival and good planification » Risks: emotional if the kidney does not work
     • Role of transplant coordinator
• A kidney transplant gives a patient one healthy kidney from a donor and a lifestyle that is closest to normal.
• Options for a kidney transplant:
     • A kidney from a blood relative (living related donor)
     • A kidney from a non-blood relative, spouse, or friend (living nonrelated donor)
     • A deceased donor kidney (from someone who has died)
• A transplant is not a cure for kidney disease, it is another form of treatment.
• A transplant may last 5,10,20, or more years - or it may not work at all.
• On average, between 89 and 95% of transplanted kidneys work for one year after surgery.
• The most common problem after surgery is rejection - the body's immune system see the transplant as "foreign" and attacks it
• A severe shortage of deceased donor organs for transplant means that people who want one may have to wait a long time.

Who can have a transplant?
• Up to 40% of ESRD patients are suitable (not if serious heart or lung disease or cancer)
• Usually no age limit but.
• Not suitable if proven non-compliance

Who can donate a kidney?

• Almost anyone can donate a kidney to a loved one
• Best donors: identical twin, non-identical twin, first degree (but also more distant) relative, spouse, close friend, or partner between 18 and 70 years old who is healthy and willing

Who can not donate a kidney?
• HIV or AIDS-related infection
• Hepatitis B or C infection
• Major heart or breathing problems
• Diabetes
• Extreme obesity
• Significant kidney disease
• Most cancers
• IV drug abuse
• Pregnancy
• High BP
• Having only one kidney
• Evidence of financial or non-financial coercion
• Inability to give informed consent/psychiatric disorders

Removing the kidney from the donor
• Open nephrectomy : usual technique; much larger scar; longer recovery; reduced risk of complications during the operation; return to work after about 3 months
• Laparoscopic nephrectomy: smaller sear and shorter recovery; longer operation; potential damage to the donated kidney; return to work within 1 month

• General anaesthesia and lasts about 2-3 hours
• Incision into the abdomen, right or left, below the navel
Patient's own kidneys are usually left in place 
• Transplant kidney is placed lower in theabdomen, just above the groin

Do you have to be on dialysis first?
• Depends on unit and national policy
• Patient can be put on a waiting list when GFR is < 20 ml/rnin/1.73m (true for new pts or those with a failing transplant)
• Sense of fairness would not allow that given the shortage of kidneys for transplantation
• Best chance to escape dialysis if living donor

Post-operative monitoring of recipient
• Very close monitoring in the first few days (serum creatinine, fluid intake and urine output, blood pressure)
• Usually two weeks stay in hospital
• Afterwards, visits at the clinic at a slowly decreasing frequency
• Return to normal activities after 3-6 months      

A difficult balance : to dampen down the immune system enough to stop it rejecting the grafted kidney, while keeping it active enough to fight infection.
• Various combinations of drugs (steroid, cyclosporin/tacrolimus, azathioprine/MMF) that MUST be taken continuously
• Danger : many interactions with other medications causing either of the IS drugs (mostly cyclosporin and tacrolimus) to work too well (toxicity) or less well (risk of rejection)

Possible problems after transplantation
• Rejection -acute -chronic
• Drug side effects
• Infection
• Card io-vascular disease
• Cancer
• l.ymphoma

Acute rejection of transplanted Kidney
• Very common (in about 40% of patients in the first year post-transplant and mostly in the first few weeks) 
• May also happen at any time if IS drugs are stopped!
• Can cause pain and fever but mostly, increase in serum creat. [one must first rule out other causes (urologic, vascular) before biopsy!
• If biopsy confirms rejection : treatment with steroid 'pulses' or stronger IS drugs : this usually works

Chronic rejection of transplanted Kidney

• More appropriately named 'transplant nephropathy'
• Usually starts after the first year
• Usually slowly progressive
• Diagnostic: transplant biopsy
• Confusion possible with cyclosporin toxicity

Drug side effects
1. Cyclosporin and tacrolimus: most important drugs for rejection prevention; work in a similar way;
if doses too high, induces renal toxicity (decrease' renal function and increase blood pressure); but if too low, risk of rejection is high; cyclosporin can also cause gum hypertrophy and excessive growth of hair; tacrolimus can cause hair loss and trembling; mostly tacrolimus can induce diabetes (in up to 10% of patients) -> lifelong need of insulin; both can damage the liver and nervous system.

2. Sirolimus; also a calcineurin inhibitor but no renal toxicity; major side effect: very high serum cholesterol levels

3 Azathioprine and mycophenolate mofetil: effective drugs but can suppress activity in the bone marrow —> anemia, neutropenia(4-ability to fight infection) and thrombocytopenia (—> bleeding tendency): stopping or decreasing the dose puts matters right; azathioprine can cause damage to the liver; MMF can cause abdominal pain and diarrhea

4. Prednisolone: a steroid and as such many problems; thinning of the skin, facial swelling, acne, diabetes, high BP, osteonecrosis (mostly in the hips —> prosthesis may become needed), osteoporosis (prevention by calcium and Vit.D)

• Immunosuppression but not as in AIDS
• Particular problem :CMV (for cytomegalovirus) infection that can be a severe illness contrary to a 'flu-like mild disease in the general population (Risk increased if donor + and patient -) but can be treated (ganciclovir injections)

Cardiovascular problems
• Continuation of the previous effects of CKD : increased risk of MI, stroke and peripheral arteritis
• Importance of controlling blood pressure (< 120/70) with low salt diet and antihypertensive drugs, diabetes (de novo) with oral or insulin treatment, cholesterol levels with statins (<180 mg/dl or 5 mmol/1) and weight (+ no smoking and exercise)
• Also interest of low doses of aspirin

• 2-5% of transplant patients develop lymphoma
• 60% of cases occur in the first year post-transplant
• Average time about 9 months after transplantation
• More common after stronger immune-suppression
• Treatment with high doses of chemotherapy and often with stopping immune-suppressants—>loss of kidney • Mortality rate: 30-50% within 2 years

• Due to immune-suppression
• Higher frequency of some types (not breast or lung), especially skin (3 times more likely) —> strong "sun block' cream to avoid sunburn
• Exposure to the sun greatly increases the risk (in Australia, the risk is increased 40 times!)
• Not a major problem if diagnosed and removed in good time

• A successful kidney transplant is a more effective treatment for kidney failure than either PD or HD
• Not all patients are suitable for kidney transplant Transplant doesn't always last for ever.
• Transplants from living donors last longest
• If transplant fails, patients can go back to dialysis. Most can have another transplant.
• Tranplantation is an integrated part of the 'integrated care' concept.

Kidney Transplantation: Treatment Options of End Stage Renal Disease - Related Hemodialysis Article


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