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Kidney Transplantation

Kidney transplants have been performed for about 50 years with excellent success, and have become a viable option for the treatment of renal (kidney) failure. In patients with end stage renal failure transplantation has been shown to have better long term prognosis than long term renal dialysis.

Anatomy and Physiology

  • There are two kidneys. Each kidney weighs about 5 -6 ounces and lies against the vertebrae and lower ribs. The kidneys lie behind the liver and colon on the right side and the stomach and pancreas on the left side (Figure 1)
  • The adrenal glands (gland that makes steroid in the body) lie over the superior surface of the kidneys
  • The kidneys are usually supplied each by a single renal artery from the aorta and single renal vein draining into the inferior vena cava
  • The ureter is a muscular tube that drains urine from the kidney into the bladder
  • The kidneys are responsible for making urine and functions to control blood salt and water balance and removal of waste products from the body
  • Blood flow to the kidney through the renal artery is filtered to remove water and waste products. This is a specialized function that is regulated by hormones, nerves and salt concentrations in the body
Figure 1 - Anatomy of the kidneys, ureters and urinary bladder. Also shown is the blood supply and blood drainage of the kidney. Note the position of the iliac arteries and veins to which a donor kidney is attached, © J. Mack

Pathology

  • Failure of kidney function leads to end stage renal disease (ESRD) and the inability of the body to adequately remove excess water and waste products.
  • In particular, the accumulation of creatinine and urea (breakdown products of protein) and potassium may be dangerous
  • Kidney failure may occur from several causes. The most common cause in the US is diabetes, which causes closing off of the vessels in the kidney, causing slow degeneration of the kidney, leading to failure
  • The causes of kidney failure are:
    1. Hereditary or congenital - cysts in the kidney, tuberous sclerosis (with hereditary tumors), horseshoe kidneys and failure of kidney development
    2. Infection leading to renal failure
    • Reflux of urine from the bladder can cause recurrent infections of the kidneys
    • Spread of infection in the body to the kidneys via the blood stream can destroy the kidney
    1. Metabolic conditions such as diabetes, amyloidosis (waxy like deposits in the tissues), gout, hyperoxaluria (increases oxalates in the urine) and porphyria (disorder of pigment metabolism)
    2. Drug toxicities - some pain medications, antibiotics and other drugs may be toxic to the kidneys
    3. Tumors - Wilm's tumor of the kidney, renal cell cancer and myeloma
    4. Inflammation of the kidneys (glomerulonephritis) - deposition of inflammatory cells and proteins in the kidneys from several systemic diseases such as lupus
    5. Obstruction - blocked ureters, enlarged prostate and urinary stones may lead to obstruction to urinary flow with back pressure causing renal failure
    6. Injury to the kidneys

History and Exam

  • Kidney failure may affect many of the organ systems in the body:
    1. Nervous system - mental dullness and confusion, leading to coma
    2. Lungs - fluid accumulation in the lungs (pulmonary edema) that requires ventilator assistance
    3. Heart - cardiac arrest from increased blood potassium levels
    4. Gastrointestinal - stomach ulcers, nausea, anorexia (lack of appetite), pancreatitis (inflammation of the pancreas)
    5. Musculoskeletal - muscle weakness and cramps, fractures, edema
    6. Blood - anemia, bleeding tendencies
    7. Electrolytes - increased potassium, phosphorus and/or calcium
  • Dialysis - patients with renal failure usually require dialysis to assist in clearing the body of wastes. There are two predominant forms of dialysis:
    1. Hemodialysis
    • Blood is drawn from the body from a catheter in the arm or neck, passed through filters to draw out waste products before being returned to the body
    • This procedure may take several hours and carried out about 3 days a week
    1. Peritoneal dialysis
    • A special catheter is placed into the abdomen
    • Dialysate fluid is passed through the catheter into the abdomen
    • The dialysate fluid draws waste products from the blood across the peritoneal membrane, a layer of cells that lines the abdomen, into the abdomen itself
    • The dialysate fluid containing the waste products is emptied out of the abdomen
    • This may need to be done several times a day
    1. Dialysis is a cumbersome process that can adversely affect the lifestyle of a person. Complications can also occur from dialysis. Patients ideally are offered the option of transplantation early in the course of their renal failure to allow best survival and to allow adequate time for a cadaveric kidney to be allocated to them

Indications

  • Diagnosis of renal failure is made by the patient's nephrologist (medical physician who is a specialist in kidney disease) who refers the patient for transplant evaluation
  • Renal failure may have been caused by any of the causes listed above and all are indications for transplantation
  • Evaluation for transplant involves a nephrologist, transplant surgeon, transplant coordinator, psychologist and social worker
    1. Important factors discussed are the patient's physical and mental condition to withstand and understand the problems associated with transplantation
    2. The patient must understand the concept of immunosuppression medication. This medication reduces the chance that the transplanted kidney will be rejected
    3. Heart function is evaluated to be sure the patient can tolerate the surgery
    4. Blood is tested for blood group, viral studies, electrolytes and blood count
    5. Blood also checked for genes that determine compatibility with other organs (called HLA genes) and reactivity of antibodies present in the patient receiving the kidney to common antigens (called PRA - panel reactive antibodies). There are usually 6 HLA genes that are compared between a donor organ and recipient. A greater match between these usually signifies better compatibility. A higher PRA usually indicates longer waiting time for a compatible kidney
    6. Urine tests are obtained to measure protein and creatinine content
  • Once a patient is accepted as a candidate for transplantation, the patient is placed on an active waiting list. Allocation of an available cadaveric kidney is based on a point system that takes into account waiting time, antigen matching (HLA), antibody reactivity (PRA) and medical urgency. The system is administered nationally by the United Network for Organ Sharing (UNOS) and is designed to allocate organs equitably

Contraindications

  • Active infection and malignancy that cannot be cured are the only real contraindications to transplantation. If a malignancy is treated, a sufficient follow up time to rule out recurrence is required before consideration for transplant
  • Other severe medical problems such as advanced heart or lung disease are relative contraindications
  • Age by itself is not usually a contraindication with transplants being performed from infants to patients over 70 years old

Preoperative preparation

  • A patient on the waiting list for a cadaveric kidney is usually given a beeper, or a means by which he/she can be contacted immediately
  • Once a cadaveric kidney has been identified for a recipient, the patient is asked to come to the hospital at once. Cadaveric kidneys may have been obtained anywhere around the country and are viable for about 24 hours (better results if < 12 hours) out of the body (called the ischemia time). Therefore, speed of workup is essential
  • Once the patient comes to the hospital, it is important to ensure they have no active infection. Blood is drawn for a blood count and a urine analysis done to rule out an active urinary tract infection
  • If the patient is on dialysis, it is important to measure blood potassium levels. A high level (normal - 3.5 to 5 meq/l) may indicate that a patient needs emergent dialysis before surgery; a process that will take a few hours more
  • Important in the preoperative workup is a blood cross-match. White blood cells from the donor are mixed with blood drawn from the potential recipient. If there is a significant reaction, the cross-match is said to be positive and the recipient is denied the kidney due to a very high chance of rejection after the transplant

Surgical Procedure

  • The procedure is done under general anesthesia
  • A catheter is placed in the urinary bladder and the bladder filled with antibiotic solution
  • The transplant graft is usually placed in the groin and not in the back where the patients own kidneys are (heterotopic placement). This is done for ease of surgery and ease of possibility for biopsy or re-exploration of the kidney postoperatively. The patient's own kidneys are usually not removed
  • An incision is made in the groin, which is parallel to the groin line and similar to a hernia incision (Figure 2)
  • The underlying muscles are divided, until the peritoneum is reached (the sac which lines the abdomen) along with the urinary bladder.
  • The peritoneum is pushed upwards revealing the iliac blood vessels, which are the terminal branches of the aorta. The iliac vessels divide into the external iliac branches, which run down the leg, and the internal iliac vessels, which supply the pelvic organs
  • The graft is removed from it's storage in ice and excess fat trimmed off. The renal artery and vein of the donor kidney are prepared for attachment. The iliac vessels of the patient are clamped and prepared for attachment
  • The renal artery of the kidney is attached by it's end to the side of the external iliac artery of the patient (Figure 3); alternatively, the internal iliac artery is divided, and the renal and internal iliac arteries are sown end-to-end (Figure 4)
  • The end of the renal vein is attached to the side of the external iliac vein (Figure 5)
  • Once these two vessels are sutured in, the vessels are all opened and the new kidney swells and turns pinkish with the new blood supply. Urine may start to be formed and observed passing through the new ureter.
  • The ureter is prepared for attachment to the urinary bladder. The bladder muscles are divided over a 2 cm incision down to the mucosa (the innermost membrane).The mucosa is opened and the end of the ureter is attached to the mucosa. The bladder muscles are then brought together over this attachment to create a tunnel; like an artificial valve to prevent back flow of urine from the bladder to the kidney (Figure 6)
  • A stent (plastic tube) is sometimes placed through the ureter across the attachment to help in healing (Figure 7)
  • The abdomen is then closed after bringing the muscles together
Figure 2 - Two incisions (dotted lines) used for kidney transplantation. © J. MackFigure 3 - The cut end of the donor renal artery is attached to the side of the external iliac artery. © J. Mack
Figure 4 - Alternatively the end of the renal artery may be attached to the end of the cut internal iliac artery. © J. MackFigure 5 - The end of the donor kidney vein is attached to the side of the external iliac vein
Figure 6 - The cut end of the ureter of the donor kidney is attached to the patient's bladder. An incision is made in the muscle wall of the bladder to the mucosa. Left. The mucosa is opened and the edge of the mucosa sutured to the end of the ureter. Right. The muscle wall is then closed around the ureter. © J. MackFigure 7 - The completed transplant. An alternative attachment of the ureter is end to end suture of the donor and recipient ureters over a stent. KidneyTransplant4.jpg, © J. Mack

Living Donor Kidney Transplantation

  • The concept of using a living rather than a cadaveric donor for a kidney is not new. The first transplants ever performed were between twins. Living donation has the advantage of increased genetic matching (if between family members), shorter time on the waiting list and shorter ischemic times out of the body with a better chance of the graft functioning
  • Special rules exist over allocation of cadaveric kidneys across the country, and living donation of kidneys from friends/relatives is a way to shorten waiting times for some patients
  • Potential donors also need an extensive workup to ensure that they are fit to undergo the operation and that they do not have any kidney problems and are able to donate one of their kidneys without risk of their own kidney failure later
  • The two operations (donor and recipient) are usually performed simultaneously. Once the donor kidney is removed, it is immediately placed in the recipient
  • The donor usually has an incision made over the flank below the ribs. The kidney is removed along with the kidney's renal artery, vein and ureter. Donors may stay 2-3 days in the hospital after the procedure
  • Newer methods include the use of minimally invasive surgery (laparoscopic surgery) to remove the donor kidneys. Most large centers use laparoscopic donation procedures. Advantages include less postoperative pain, and shorter hospital stays (1-2 days)

Immunosuppression Medications

  • The body recognizes the transplant organ as being something foreign to the body (foreign antigen) and tries to reject it. The body's immune cells attack the donor kidney
  • Medications to suppress the immune system have developed over the past few decades as rejection is better understood
  • Patients are usually started on a combination of anti-rejection drugs after surgery. Levels of these drugs are usually measured on a daily basis until stabile after surgery
  • Patients are maintained on these drugs for the rest of the life of the graft although some of the drugs may be weaned down over a period of time

Complications

  • Delayed graft function
    1. The kidney may not function immediately after transplant. This may be because of prolonged ischemia time or donor factors
    2. The kidney usually has some minor damage to tubular cells within the kidney (called acute tubular necrosis - ATN). This may take a few days to resolve. In the meantime, the patient may require dialysis
  • Rejection
    1. This is a situation in which the body rejects the transplanted kidney
    2. Rejection is seen in two forms - acute and chronic
    3. Acute rejection is usually diagnosed by a patient having decreased urine output, painful swelling of the graft and a rising blood creatinine level within a few months after surgery
      • The patient usually requires an ultrasound to rule out obstruction or clotting of the blood vessels to the kidney
      • A biopsy of the kidney is then obtained under ultrasound guidance to confirm rejection
      • Acute rejection is usually treated with an increase in immunosuppression drugs over a period of time. More severe acute rejections may need the use of specialized antibodies against immune cells
    4. Chronic rejection is a slow progressive destruction of the transplanted kidney that may take several years. No therapy is satisfactory in treating this and the patient may need re-transplantation
  • Vascular complications
    1. Thrombosis or clotting of the vessels may be serious with high rates of kidney loss. If diagnosed within an hour, re-operation and removal of clots may salvage the graft but, in general, success rates are low
    2. Narrowing of the vessels may occur several months after the surgery. These may sometimes be amenable to angioplasty (dilating the vessel with a balloon catheter- See Angiography)
  • Ureter complications
    1. Leak of urine from the ureter attachment to the bladder may produce a urine collection which may get infected. This may be treated by placing a stent in the ureter with drainage or with ureter reattachment
    2. Narrowing of the ureter attachment may cause obstruction of urine flow and swelling of the kidney with eventual failure. This may be treated by stenting or reattachment
  • Lymphatic complications. Failure to tie off lymphatic vessels around the iliac vessels can result in leakage of lymph causing a collection known as a lymphocele. This can get infected or cause obstruction of the ureter or blood vessels. It is usually treated by draining this collection of fluid into the peritoneum where the lymph gets absorbed
  • Infections
    1. Suppression of the immune system leads to an increased risk of developing infection. Transplant patients are often put on long term antibiotics to prevent such infections
    2. Patients must be aware of their increased risk for infections and infections in these patients must be aggressively treated
    3. Common infections include:
      • Viral - herpes, cytomegalovirus and Epstein Barr virus may affect various organ systems in the body and are associated with low grade fever, low blood count and flu like symptoms
      • Fungal - yeast infections of the throat or genital tract are common
      • Bacterial - lung, urinary tract and wound infections
  • Complications of long term immunosuppression include increased risk of developing infection (see above), cancer and specific side affects of each medication
    1. Some of the specific side affects of commonly used drugs are:
      • Cyclosporine - may cause hypertension, kidney and liver toxicity, swelling of the gums, increased hair growth and tremors
      • Prograf (tacrolimus) - may cause kidney toxicity, diabetes, nerve toxicity, heart muscular dysfunction and hypertension
      • Cellcept (mycophenolate mofetil) - may cause low blood counts and gastroenteritis (inflammation of the lining of the stomach and bowel)
      • Steroids - may cause fluid retention, stomach ulcers, diabetes, pancreatitis, hormonal imbalance and poor wound healing
    2. Cancer
      • The incidence of malignancy is increased in transplant patients due to immunosuppression
      • Transplant patients need to follow appropriate screening protocols for cancers
      • The most common cancer is of the skin. Transplant patients are advised to follow sunscreen precautions and see a dermatologist every year

Postoperative care

  • After the operation the patient is monitored closely for urine output
  • A patient may make over 500 cc/hr of urine if the kidney works well
  • The patient needs adequate fluid volume to catch up with urinary losses
  • The bladder catheter may need irrigation due to blood clots from surgery blocking it. The catheter is removed in 1 -2 days if urine output is good
  • Usually a fall in blood creatinine is seen after the surgery reaching normal levels in a few days
  • The patient is usually started on a diet the same day and is also placed on stool softeners to prevent constipation
  • Patients may need narcotic pain relievers for a few days
  • Patients are started on long term antibiotic medications for prevention of bacterial, viral and fungal infections
  • Antacids are also started due a higher incidence of gastritis from steroid use
  • Many patients are placed on calcium supplements
  • Patients are usually discharged in 4-5 days. Staples or sutures are removed in 3 weeks
  • Patients are usually followed closely over the first few months to monitor immunosuppression levels