Haemodialysis - blood from the patient is pumped through an array of semipermeable membranes which brings blood into close proximity with dialysate (a solution with a different concentration of waste products which allows waste products from the blood to diffuse into the solution).
haemofiltration - removal of plasma water and its dissolved constituents by convective flow across high-flux semipermeable membrane and replacing it with a solution of desired biochemical composition.
peritoneal dialysis - uses peritoneal membrane as semipermeable membrane avoiding need for extracorporeal circulation of blood. a tube is inserted into the peritoneal cavity through anterior abdominal wall. dialysate is run into the peritoneal cavity usually usually under gravity. urea, creatinine, phosphate and other uraemic toxins pass into the dialysate down the concentration gradient. water is attracted into the peritoneal cavity by osmosis depending on osmolarity of dialysate, which is determined by the glucose or polymer content of the dialysate. the fluid is changed regularly to repeat the process.
Reference: Kumar and Clark
Monica
Monday, June 2, 2008
Thursday, May 29, 2008
Tests for kidney donors
Blood Type. The first step is to determine your blood type. There are four blood types, designated by the presence or absence of two antigens—the A antigen and the B antigen. Blood type A means you have the A antigen. Type B means you have the B antigen. Type AB means you have both antigens. Type O means you have neither antigen.
You must have a blood type compatible with the recipient or you will not be able to donate. Here is who can donate to whom:
Type A can donate to types A and AB.
Type B can donate to types B and AB.
Type AB can donate to type AB.
Type O can donate to types A, B, AB, and O.
If you and your potential recipient are not of the same blood type, there are two things you can consider. One option is called "paired exchange." Paired exchange involves finding another donor-recipient pair who have incompatible blood types but your blood type is compatible with the other recipient, and the other donor's blood type is compatible with your potential recipient's blood type. In that situation, you donate to the other recipient, and the other donor donates to your recipient. This web page illustrates how paired exchange works.
The other option is called "plasmapheresis." Plasmapheresis involves the transplant recipient undergoing removal of the spleen and a special medical process that removes the blood's incompatible antigens. With removal of the recipient's antigens, the donor is able to donate.
Tissue Type. A second test of compatibility looks at the match of human leukocyte antigens (HLA). There are many different kinds of antigens, but there are three categories assessed for kidney donation, designated HLA-A, HLA-B, and HLA-DR. You inherit one set of these three antigens from each parent giving you a total of six HLAs.
Your antigens are determined by drawing blood and testing it. A similar test is run for the recipient, and the antigens are compared. The closer the match the better because the recipient is less likely to reject the donated organ. You might hear of a "six-of-six" match (all donor and recipient antigens match) or a "half match" (three of the six antigens are the same) or a "zero match" (none of the antigens matches).
There was a time when tissue compatibility was important. However, the development of more effective anti-rejection drugs has reduced the importance of the HLA match. In fact, some transplant teams ignore tissue typing. Therefore, even if your degree of matching with the donor is relatively low, you may still be considered for donation.
http://www.aarexindia.com/kidney.asp
www.livingdonorsonline.org/kidney/kidney4.htm
You must have a blood type compatible with the recipient or you will not be able to donate. Here is who can donate to whom:
Type A can donate to types A and AB.
Type B can donate to types B and AB.
Type AB can donate to type AB.
Type O can donate to types A, B, AB, and O.
If you and your potential recipient are not of the same blood type, there are two things you can consider. One option is called "paired exchange." Paired exchange involves finding another donor-recipient pair who have incompatible blood types but your blood type is compatible with the other recipient, and the other donor's blood type is compatible with your potential recipient's blood type. In that situation, you donate to the other recipient, and the other donor donates to your recipient. This web page illustrates how paired exchange works.
The other option is called "plasmapheresis." Plasmapheresis involves the transplant recipient undergoing removal of the spleen and a special medical process that removes the blood's incompatible antigens. With removal of the recipient's antigens, the donor is able to donate.
Tissue Type. A second test of compatibility looks at the match of human leukocyte antigens (HLA). There are many different kinds of antigens, but there are three categories assessed for kidney donation, designated HLA-A, HLA-B, and HLA-DR. You inherit one set of these three antigens from each parent giving you a total of six HLAs.
Your antigens are determined by drawing blood and testing it. A similar test is run for the recipient, and the antigens are compared. The closer the match the better because the recipient is less likely to reject the donated organ. You might hear of a "six-of-six" match (all donor and recipient antigens match) or a "half match" (three of the six antigens are the same) or a "zero match" (none of the antigens matches).
There was a time when tissue compatibility was important. However, the development of more effective anti-rejection drugs has reduced the importance of the HLA match. In fact, some transplant teams ignore tissue typing. Therefore, even if your degree of matching with the donor is relatively low, you may still be considered for donation.
http://www.aarexindia.com/kidney.asp
www.livingdonorsonline.org/kidney/kidney4.htm
Important Complications
Kidney failure (from any cause), if severe enough, can affect almost any body organ. Here are the complications most commonly seen with advanced kidney failure:
High Blood Pressure: It can be both a cause and a complication of kidney failure. It tends to develop relatively early and if left uncontrolled, it can cause your kidneys to fail faster and place you at increased risk for heart disease.
Anemia: Most people with advanced kidney failure have a low red blood cell count or anemia. Your kidneys can’t produce enough of the hormone needed to make your red blood cells. Iron deficiency is also a common problem.
Malnutrition: Loss of appetite often causes low energy and protein intake. In some ways this can be good since decreased protein intake can help lead to less buildup of toxins created by protein breakdown. But if you end up getting too little energy and protein, you will become malnourished.
Bone Disease: Kidney failure can cause disorders of Vitamin D, calcium and phosphorous. This can lead to serious bone disease as well as increased risk for minerals depositing throughout your body. Mineral deposition outside of the bones can have serious consequences, particular for the heart and blood vessels.
Nerve Disorders: Your nerves and the brain are particularly sensitive to the build up of toxins (called uremia). This can cause symptoms ranging from sleep and memory difficulties to complete confusion and coma. Worsening nerve symptoms is an important criteria used by your doctor to help decide if you need dialysis or not.
Amyloidosis: Normal kidneys filter excess proteins from the blood, thus preventing levels from getting too high. When the kidneys don't work properly, as in patients receiving dialysis, another type of protein called beta-2-microglobulin may build up in the blood. When this occurs, beta-2-microglobulin molecules may join together, like the links of a chain, forming a few very large molecules from many smaller ones. These large molecules can form deposits and eventually damage the surrounding tissues and cause great discomfort. This condition is called dialysis-related amyloidosis (DRA).
Functioning & Well-Being: An increasing number of symptoms, worsening physical functioning, depression, disability, and social isolation can be seen with worsening kidney function. These types of complications are often the least monitored by doctors and other health care providers.
Heart Disease:There is an increased risk for heart attacks, heart failure, strokes, and blood vessel disease with chronic kidney disease (CKD) and kidney failure. If you have CKD, you are considered in the “highest risk” group for “cardiovascular disease”, and you should have all your risk factors treated as aggressively as possible.
--> here's a good website showing the urinary system
http://www.medindia.net/animation/anatomy_urinary.asp
High Blood Pressure: It can be both a cause and a complication of kidney failure. It tends to develop relatively early and if left uncontrolled, it can cause your kidneys to fail faster and place you at increased risk for heart disease.
Anemia: Most people with advanced kidney failure have a low red blood cell count or anemia. Your kidneys can’t produce enough of the hormone needed to make your red blood cells. Iron deficiency is also a common problem.
Malnutrition: Loss of appetite often causes low energy and protein intake. In some ways this can be good since decreased protein intake can help lead to less buildup of toxins created by protein breakdown. But if you end up getting too little energy and protein, you will become malnourished.
Bone Disease: Kidney failure can cause disorders of Vitamin D, calcium and phosphorous. This can lead to serious bone disease as well as increased risk for minerals depositing throughout your body. Mineral deposition outside of the bones can have serious consequences, particular for the heart and blood vessels.
Nerve Disorders: Your nerves and the brain are particularly sensitive to the build up of toxins (called uremia). This can cause symptoms ranging from sleep and memory difficulties to complete confusion and coma. Worsening nerve symptoms is an important criteria used by your doctor to help decide if you need dialysis or not.
Amyloidosis: Normal kidneys filter excess proteins from the blood, thus preventing levels from getting too high. When the kidneys don't work properly, as in patients receiving dialysis, another type of protein called beta-2-microglobulin may build up in the blood. When this occurs, beta-2-microglobulin molecules may join together, like the links of a chain, forming a few very large molecules from many smaller ones. These large molecules can form deposits and eventually damage the surrounding tissues and cause great discomfort. This condition is called dialysis-related amyloidosis (DRA).
Functioning & Well-Being: An increasing number of symptoms, worsening physical functioning, depression, disability, and social isolation can be seen with worsening kidney function. These types of complications are often the least monitored by doctors and other health care providers.
Heart Disease:There is an increased risk for heart attacks, heart failure, strokes, and blood vessel disease with chronic kidney disease (CKD) and kidney failure. If you have CKD, you are considered in the “highest risk” group for “cardiovascular disease”, and you should have all your risk factors treated as aggressively as possible.
--> here's a good website showing the urinary system
http://www.medindia.net/animation/anatomy_urinary.asp
KIDNEY FAILURE
WHAT CAUSES RENAL FAILURE?
Kidney failure can occur from an acute situation or from chronic problems. In acute renal failure, kidney function is lost rapidly and can occur from a variety of insults to the body. The list of causes is often categorised based on where the injury has occurred.
Prerenal causes (before the kidney) are due to the decreased blood supply to the kidneys. Examples of prerenal causes are
· Hypovolemia (low blood volume) due to blood loss.
· Dehydration from loss of body fluid( vomiting, diarrhoea, sweating and fever)
· Medication, for example, diuretics may cause excessive water loss
· Loss of blood supply to the kidney due to obstruction of the renal artery or vein.
Renal causes (damage directly to the kidneys) include
· Sepsis: the body’s immune system is overwhelmed from infection and causes inflammation and shutdown of the kidneys. This does not occur with urinary tract infections
· Medications: some medications are toxic to the kidney, including nonsteroidal anti –inflammatory drugs like naproxen. Others are antibiotics, iodine containing medications such as those injected for radiology dye studies.
· Rhabdomyolysis: this is a situation in which there is significant muscle breakdown in the body and the degeneration products of the muscle fibers clog the filtering system of the kidneys. often occurring because of trauma and crush injuries.
· Multiple myeloma
· Acute glomerulonephritis-inflammation o the glomeruli.
Post renal causes (after the kidney) are due to the factors that affect the outflow of the urine
· Obstruction of the bladder or the ureters can cause back pressure when there is no place for the urine to go as the kidneys continue to work. When the pressure increases enough, the kidneys shut down.
· Prostatic hypertrophy or prostate cancer may block the urethra and prevents the bladder from emptying.
· Tumors in the abdomen that surround and obstruct the ureters.
· Kidney stones
Chronic renal failure develops over months and years. the most common renal failures are related:
· Poor controlled diabetes.
· Poor controlled high blood pressure.
Kidney failure can occur from an acute situation or from chronic problems. In acute renal failure, kidney function is lost rapidly and can occur from a variety of insults to the body. The list of causes is often categorised based on where the injury has occurred.
Prerenal causes (before the kidney) are due to the decreased blood supply to the kidneys. Examples of prerenal causes are
· Hypovolemia (low blood volume) due to blood loss.
· Dehydration from loss of body fluid( vomiting, diarrhoea, sweating and fever)
· Medication, for example, diuretics may cause excessive water loss
· Loss of blood supply to the kidney due to obstruction of the renal artery or vein.
Renal causes (damage directly to the kidneys) include
· Sepsis: the body’s immune system is overwhelmed from infection and causes inflammation and shutdown of the kidneys. This does not occur with urinary tract infections
· Medications: some medications are toxic to the kidney, including nonsteroidal anti –inflammatory drugs like naproxen. Others are antibiotics, iodine containing medications such as those injected for radiology dye studies.
· Rhabdomyolysis: this is a situation in which there is significant muscle breakdown in the body and the degeneration products of the muscle fibers clog the filtering system of the kidneys. often occurring because of trauma and crush injuries.
· Multiple myeloma
· Acute glomerulonephritis-inflammation o the glomeruli.
Post renal causes (after the kidney) are due to the factors that affect the outflow of the urine
· Obstruction of the bladder or the ureters can cause back pressure when there is no place for the urine to go as the kidneys continue to work. When the pressure increases enough, the kidneys shut down.
· Prostatic hypertrophy or prostate cancer may block the urethra and prevents the bladder from emptying.
· Tumors in the abdomen that surround and obstruct the ureters.
· Kidney stones
Chronic renal failure develops over months and years. the most common renal failures are related:
· Poor controlled diabetes.
· Poor controlled high blood pressure.
Wednesday, May 28, 2008
Advantages and Disadvantages of Dialysis and Transplant
Kidney Dialysis
Dialysis involves the removal of wastes from the blood of a patient suffering from kidney failure. The two forms of dialysis are:
Haemodialysis – when a machine cleans the patient’s blood, acting as an artificial kidney; it requires access to a large blood vessel with fast blood flow
There are three main ways access to a large blood vessel is created:
- An Arterio-Venous Fistula (AVF): the patient undergoes a small operation to join an artery and a vein together, so that the blood from the flows into the patient’s more superficial vein, making it larger and stronger for dialysis
- A prosthetic/artificial graft: if the patient’s blood vessels cannot make a fistula (e.g. small, weak or damaged veins), their artery and vein can be joined together by soft tubing during surgery
- A vascular access catheter: a temporary tube placed into a large vein belonging to the patient, consisting of 2 channels: one to redirect the blood into the dialysis machine and the other to return the clean blood
| Advantages | Disadvantages |
| Minimal participation in the treatment (staff performs dialysis at centre) No external access required No equipment/supplies or home supports required | Patients are required to adhere to specific schedules Patients must travel to the dialysis centre Strict diet control and fluid control Complications may arise e.g. low BP, lightheadedness, shortness of breath, cramps, nausea and vomiting Access can become infected or develop blood clots |
Peritoneal dialysis (PD) – a PD catheter (a soft plastic tube) is inserted into the patient’s body around their abdomen, with a part of the tube staying outside of the body. Dialysis fluid moves in and out of the body through this catheter to clean the patient’s blood.
| Advantages | Disadvantages |
| More flexible scheduling – the exact timing of the procedure can be altered PD can be performed at home Less strict diet and fluid control than haemodialysis No daytime exchange (daytime dwell) if patient chooses to have dialysis at night | Infection – the PD catheter is a potential site for the entry of bacteria into the body Requires someone be trained in the use of equipment at home Increased risk of hernia (weakening of abdominal muscles) Permanent external catheter – changes to body image Possible weight gain due to glucose absorption from dialysis fluid |
Kidney Transplant
A patient with kidney failure receives a new kidney from a living or deceased donor. When a donor kidney becomes available a patient is chosen with the best blood and tissue match. However, lifelong treatment with immunosuppressant drugs will be required if the kidney donor is not related. Receiving a kidney from an identical twin or a close relation provides the best possibility for the kidney to not be rejected.
| Advantages | Disadvantages |
| Quality of life and survival often improved compared to the use of dialysis Patients are free of the time- and energy-consuming nature of dialysis Regular dietary requirement Fewer visits to the clinic | Shortage of kidney organs available – the average wait for a deceased donor kidney about 4 years Risks associated with surgical procedure e.g. infection, bleeding, damage to other organs Lifetime treatment regimen of immunosuppressive medications, with possible side effects Patient must satisfy a number of factors to be a possible transplant candidate Risk of transplant rejection |
Conditions that exclude a patient from being eligible for a kidney transplant include:
- old age
- severe heart or vascular disease
- untreated current infection
- active or recently treated cancer
- chronic illness that results in a life expectancy of less than a few years
- Poorly controlled mental illness (psychosis)
- Severe obesity (a body mass index greater than 40)
- Inability to remember medications
- Active drug or alcohol abuse
- Positive for HIV
Sources:
http://www.uptodate.com/patients/content/topic.do?topicKey=kidn_dis/6131
Tuesday, May 27, 2008
Is 50% kidney Function Enough
Is 50% renal function enough?? By Josh
Glomerular Filtration Rate (GFR)
Glomerular filtration rate (GFR) measures how efficiently the kidney is working. It uses a percentage to convey the result i.e. 90% indicates the kidney is functioning at 90% of normal capacity. Until recently a GFR was deduced from taking a 24 hour urine sample after injecting a substance into the bloodstream. Now days GFR can be measured by checking creatine levels in a blood sample. Creating comes from the breakdown of muscle. Kidney’s filter the blood and thus take out the creating so a high level of creatine in blood would indicate a kidney operating at a low percentage (How your kidney’s work)
Levels of Kidney Failure
• Increased risk of CKD. A GFR of 90 or above is considered normal. Even with a normal GFR, you may be at increased risk for developing CKD if you have diabetes, high blood pressure, or a family history of kidney disease. The risk increases with age: People over 65 are more than twice as likely to develop CKD as people between the ages of 45 and 65. African Americans also have a higher risk of developing CKD.
• Stage 1: Kidney damage with normal GFR (90 or above). Kidney damage may be detected before the GFR begins to decline. In this first stage of kidney disease, the goals of treatment are to slow the progression of CKD and reduce the risk of heart and blood vessel disease.
• Stage 2: Kidney damage with mild decrease in GFR (60 to 89). When kidney function starts to decline, your health care provider will estimate the progression of your CKD and continue treatment to reduce the risk of other health problems.
• Stage 3: Moderate decrease in GFR (30 to 59). When CKD has advanced to this stage, anemia and bone problems become more common. Work with your health care provider to prevent or treat these complications.
• Stage 4: Severe reduction in GFR (15 to 29). Continue following the treatment for complications of CKD and learn as much as you can about the treatments for kidney failure. Each treatment requires preparation. If you choose hemodialysis, you will need to have a procedure to make a vein in your arm larger and stronger for repeated needle insertions. For peritoneal dialysis, you will need to have a catheter placed in your abdomen. Or you may want to ask family or friends to consider donating a kidney for transplantation.
• Stage 5: Kidney failure (GFR less than 15). When the kidneys do not work well enough to maintain life, you will need dialysis or a kidney transplant.
Dot points taken from http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/
Bibliography
How you kidney’s work
http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/
Glomerular Filtration Rate (GFR)
Glomerular filtration rate (GFR) measures how efficiently the kidney is working. It uses a percentage to convey the result i.e. 90% indicates the kidney is functioning at 90% of normal capacity. Until recently a GFR was deduced from taking a 24 hour urine sample after injecting a substance into the bloodstream. Now days GFR can be measured by checking creatine levels in a blood sample. Creating comes from the breakdown of muscle. Kidney’s filter the blood and thus take out the creating so a high level of creatine in blood would indicate a kidney operating at a low percentage (How your kidney’s work)
Levels of Kidney Failure
• Increased risk of CKD. A GFR of 90 or above is considered normal. Even with a normal GFR, you may be at increased risk for developing CKD if you have diabetes, high blood pressure, or a family history of kidney disease. The risk increases with age: People over 65 are more than twice as likely to develop CKD as people between the ages of 45 and 65. African Americans also have a higher risk of developing CKD.
• Stage 1: Kidney damage with normal GFR (90 or above). Kidney damage may be detected before the GFR begins to decline. In this first stage of kidney disease, the goals of treatment are to slow the progression of CKD and reduce the risk of heart and blood vessel disease.
• Stage 2: Kidney damage with mild decrease in GFR (60 to 89). When kidney function starts to decline, your health care provider will estimate the progression of your CKD and continue treatment to reduce the risk of other health problems.
• Stage 3: Moderate decrease in GFR (30 to 59). When CKD has advanced to this stage, anemia and bone problems become more common. Work with your health care provider to prevent or treat these complications.
• Stage 4: Severe reduction in GFR (15 to 29). Continue following the treatment for complications of CKD and learn as much as you can about the treatments for kidney failure. Each treatment requires preparation. If you choose hemodialysis, you will need to have a procedure to make a vein in your arm larger and stronger for repeated needle insertions. For peritoneal dialysis, you will need to have a catheter placed in your abdomen. Or you may want to ask family or friends to consider donating a kidney for transplantation.
• Stage 5: Kidney failure (GFR less than 15). When the kidneys do not work well enough to maintain life, you will need dialysis or a kidney transplant.
Dot points taken from http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/
Bibliography
How you kidney’s work
http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/
Monday, May 26, 2008
Treatment after Transplants, and Complications of Transplants
PCL 13 - Sisters
Amber Hartley
Treatment after Transplants, and Complications of Transplants
Renal transplant offers great potential for patients in end-stage renal failure.
Advantages include:
Freedom from dietary and fluid restriction
Anaemia corrected
Infertility corrected
Need for parathyroidectomy is reduced
The kidney to be transplanted may be taken from a cadaveric donor, or from a living relative. If the kidney comes from a living relative, the donor must undergo extensive testing first. These tests include:
Clinical examination
Measurement of renal function
Tests for carriage of hepatitis B, C, HIV, and CMV
Detailed imaging of renal anatomy
Both the kidney and the associated ureter are taken from the donor, and transplanted into the recipient.
Attempts are made to match recipients and donors as closely as possible for the HLA molecule. HLA-DR antigens have been shown to have the greatest impact on transplant survival. Complete compatibility at A, B and DR points of the HLA molecule give the greatest rates of success, followed by a single HLA mismatch. However, completely mismatched kidneys are often transplanted. In all cases, unless the kidney is taken from an identical twin, immunosuppression is needed following transplantation.
Immunosuppression is lifelong and aimed at preventing the rejection of donor organs. The risk of rejection is highest in the first 3 months following transplantation. In these three months, rejection episodes occur in 30% of cases where a cadaver donor was used.
There are a number of drugs used for immunosuppression, each with different mechanisms of action and side effects.
1. Corticosteroids
o Non-specific anti-inflammatory and immunosuppressive action
o High doses can be used for acute rejection
2. Azathioprine
o Blocks purine synthesis and replication of lymphocytes, hence preventing cell-mediated rejection
o Side effects: suppression of RBC and platelet production, increased incidence of infections, hepatotoxicity.
o Cannot be used with allopurinol
3. Mycophenolate mofetil
o Blocks an enzyme required for purine synthesis, more specific for lymphocytes than for other cells
o More potent than azathioprine
o Side effects: nausea, vomiting, diarrhoea
o Can be used with allopurinol
4. Ciclosporin (CSA)
o Prevents activation of T lymphocytes in response to new antigens
o Highly effective in preventing rejection while leaving the functioning of the rest of the immune system largely intact
o Side effects: nephrotoxicity
o Minor side effects: anorexia, lethargy, hirsutism, tremor, paraesthesia (tingling sensation), gum hypertrophy, gastrointestinal disturbances
o Expensive
o Poorly absorbed by mouth but can be given orally, or intravenously by infusion.
5. Tacrolimus
o Blocks T cell activation (similar to Ciclosporin)
o More potent than CSA, hence used for acute rejection episodes, as well as maintenance of transplant
o Side effects: diabetogenic
6. Sirolimus
o Prevents entry of cell into G1 phase of cell cycle
o Side effects: poor wound healing, delay of the recovery of proximal tubular cell injury sustained during transplantation, thrombocytopenia, hyperlipidemia
7. Antibodies
o Antibodies directed against lymphocyte surface marker proteins, enabling neutralising or killing of lymphocytes
o Mainly used for treating steroid-resistant rejections and for induction therapy for high immunological risk patients.
Complications of Renal Transplants
1. Acute tubular necrosis (ATN)
o Commonest cause of cadaveric transplant dysfunction
o Associated with worse long-term outcome and rejection
2. Technical failures
o Incorrect or incomplete surgical procedure during transplantation, surgical intervention may be required
3. Acute rejection
o Seen in up to 30% of cases
4. Infection
o In the first month after transplantation, infections are those typically seen following any surgery
o CMV is common in weeks or months after transplantation
o Prophylaxis often given against Pneumocystis carinii and oral candidiasis
o Polyomavirus infections are a serious complication for transplant outcome
5. Post-transplantation lymphoproliferative disorders
6. Chronic allograft nephropathy (CAN)
o Most common cause of late graft failure
o Mediated by immunological and non-immunological factors, results in progressive, irreversible decline in transplant function
o No treatment available for this complication
7. Development of Malignancy
o Immunosuppressive drugs increase risk of cancers, including basal and squamous cell carcinoma, renal, cervical and vaginal cancers.
8. Cardiovascular disease
o Due to increased incidence of hypertension, obesity, diabetes and lipid disorders
9. Post-transplant osteoporosis
o Common following treatment with immunosuppressive steroids
Sources:
Kumar and Clark (2005), “Clinical Medicine,” 6th edition. p 678-681
Rang and Dale (2003), “Pharmacology,” 6th edition, p 242-243
Amber Hartley
Treatment after Transplants, and Complications of Transplants
Renal transplant offers great potential for patients in end-stage renal failure.
Advantages include:
Freedom from dietary and fluid restriction
Anaemia corrected
Infertility corrected
Need for parathyroidectomy is reduced
The kidney to be transplanted may be taken from a cadaveric donor, or from a living relative. If the kidney comes from a living relative, the donor must undergo extensive testing first. These tests include:
Clinical examination
Measurement of renal function
Tests for carriage of hepatitis B, C, HIV, and CMV
Detailed imaging of renal anatomy
Both the kidney and the associated ureter are taken from the donor, and transplanted into the recipient.
Attempts are made to match recipients and donors as closely as possible for the HLA molecule. HLA-DR antigens have been shown to have the greatest impact on transplant survival. Complete compatibility at A, B and DR points of the HLA molecule give the greatest rates of success, followed by a single HLA mismatch. However, completely mismatched kidneys are often transplanted. In all cases, unless the kidney is taken from an identical twin, immunosuppression is needed following transplantation.
Immunosuppression is lifelong and aimed at preventing the rejection of donor organs. The risk of rejection is highest in the first 3 months following transplantation. In these three months, rejection episodes occur in 30% of cases where a cadaver donor was used.
There are a number of drugs used for immunosuppression, each with different mechanisms of action and side effects.
1. Corticosteroids
o Non-specific anti-inflammatory and immunosuppressive action
o High doses can be used for acute rejection
2. Azathioprine
o Blocks purine synthesis and replication of lymphocytes, hence preventing cell-mediated rejection
o Side effects: suppression of RBC and platelet production, increased incidence of infections, hepatotoxicity.
o Cannot be used with allopurinol
3. Mycophenolate mofetil
o Blocks an enzyme required for purine synthesis, more specific for lymphocytes than for other cells
o More potent than azathioprine
o Side effects: nausea, vomiting, diarrhoea
o Can be used with allopurinol
4. Ciclosporin (CSA)
o Prevents activation of T lymphocytes in response to new antigens
o Highly effective in preventing rejection while leaving the functioning of the rest of the immune system largely intact
o Side effects: nephrotoxicity
o Minor side effects: anorexia, lethargy, hirsutism, tremor, paraesthesia (tingling sensation), gum hypertrophy, gastrointestinal disturbances
o Expensive
o Poorly absorbed by mouth but can be given orally, or intravenously by infusion.
5. Tacrolimus
o Blocks T cell activation (similar to Ciclosporin)
o More potent than CSA, hence used for acute rejection episodes, as well as maintenance of transplant
o Side effects: diabetogenic
6. Sirolimus
o Prevents entry of cell into G1 phase of cell cycle
o Side effects: poor wound healing, delay of the recovery of proximal tubular cell injury sustained during transplantation, thrombocytopenia, hyperlipidemia
7. Antibodies
o Antibodies directed against lymphocyte surface marker proteins, enabling neutralising or killing of lymphocytes
o Mainly used for treating steroid-resistant rejections and for induction therapy for high immunological risk patients.
Complications of Renal Transplants
1. Acute tubular necrosis (ATN)
o Commonest cause of cadaveric transplant dysfunction
o Associated with worse long-term outcome and rejection
2. Technical failures
o Incorrect or incomplete surgical procedure during transplantation, surgical intervention may be required
3. Acute rejection
o Seen in up to 30% of cases
4. Infection
o In the first month after transplantation, infections are those typically seen following any surgery
o CMV is common in weeks or months after transplantation
o Prophylaxis often given against Pneumocystis carinii and oral candidiasis
o Polyomavirus infections are a serious complication for transplant outcome
5. Post-transplantation lymphoproliferative disorders
6. Chronic allograft nephropathy (CAN)
o Most common cause of late graft failure
o Mediated by immunological and non-immunological factors, results in progressive, irreversible decline in transplant function
o No treatment available for this complication
7. Development of Malignancy
o Immunosuppressive drugs increase risk of cancers, including basal and squamous cell carcinoma, renal, cervical and vaginal cancers.
8. Cardiovascular disease
o Due to increased incidence of hypertension, obesity, diabetes and lipid disorders
9. Post-transplant osteoporosis
o Common following treatment with immunosuppressive steroids
Sources:
Kumar and Clark (2005), “Clinical Medicine,” 6th edition. p 678-681
Rang and Dale (2003), “Pharmacology,” 6th edition, p 242-243
Subscribe to:
Posts (Atom)