Renal Transplantation/Kidney Transplant provides superior outcomes to dialysis as a treatment for end-stage kidney disease. Therefore, it is essential that kidney transplantation be part of an integrated treatment and management plan for chronic kidney disease (CKD). Developing an effective national program of transplantation is challenging because of the requirement for kidney donors and the need for a multidisciplinary team to provide expert care for both donors and recipients.
Kidney transplantation is the treatment of choice in patients with end-stage renal disease or severe chronic kidney disease as it improves the quality of life and has better survival advantages compared to dialysis. Various factors merit consideration to match the donor kidney with the recipient, as the donor kidney act as an alloantigen. In general, when transplanting tissue or cells from a genetically different donor to the graft recipient, the alloantigen of the donor induces an immune response in the recipient against the graft. This response can destroy the graft if not controlled. The whole process is called allograft rejection.[rx]
Allograft rejection is inflammation with specific pathologic changes in the allograft, due to the recipient’s immune system recognizing the non-self antigen in the allograft, with or without dysfunction of the allograft.
Types of Kidney Transplant
Both innate and adaptive immune systems play a significant role in rejection, But the T lymphocytes are the principal cells that recognize the allograft. There are other costimulatory molecules, and cytokines also play a major role in this reaction. Depending on the histopathology and immunological characteristics, the renal transplant rejections can be classified broadly under the following categories :
- Hyperacute rejection – Happens minutes after transplant, and it is related to the preformed antibody or ABO incompatibility; this is rarely seen now due to the very sensitive cross-match tests performed before the transplant.
- Acute rejection – This can happen any time after transplant, usually within days to weeks after transplant. It classifies into the following:
- Antibody-mediated rejection- ABMR – which usually demonstrates evidence of circulating donor-specific alloantibodies and immunological evidence of antibody-mediated injuries to the kidney. Like inflammation of glomeruli (Glomerulitis) or peritubular capillary (peritubular capillaritis).
- Acute T-cell mediated rejection- TCMR: which characterized by lymphocytic infiltration of the tubules, interstitium, and sometimes the arterial intima.
- Chronic rejection – It usually develops more than three months post-transplant. It can either be chronic antibody-mediated rejection or chronic T cells mediated rejection.
A mixture of acute rejection superimposed on chronic rejection.
- The Banff classification, originally founded in 1991 and later updated in 2007, 2009, 2013, and 2017 established specific criteria for the diagnosis of kidney allograft rejection.[rx] Based on the 2017 revised Banff criteria, CAAMR and CATMR are diagnosed and classified as follows:
I) CAAMR (all criteria must be present):
1. Histological evidence of chronic tissue injury (one or more of the following)
Transplant glomerulopathy without evidence of thrombotic microangiopathy or glomerulonephritis
Severe multilayering of the glomerular basement membrane on electron microscopy
New-onset arterial intimal fibrosis
2.Evidence of antibody interaction with vascular endothelium (one or more of the following)
Linear C4d deposition of peritubular capillaries
Moderate or severe microvascular inflammation in the absence of glomerulonephritis
Increased gene expression of gene transcripts strongly suggests antibody-mediated rejection
3. Positive DSA Antibodies to HLA and non-HLA antigens.
II) CATMR is classified as follows (after ruling out other causes of IFTA)
Grade IA – More than 25% interstitial inflammation of the cortex with “moderate tubulitis” in 1 or more tubules, excluding severely atrophic tubules.
Grade IB – Greater than 25% interstitial inflammation of the cortex with “severe tubulitis” in 1 or more tubules, excluding severely atrophic tubules
Grade II – Chronic allograft arteriopathy indicated by neointima formation, intimal arterial fibrosis, and mononuclear infiltration
Causes of Kidney Transplant
- Congenital, familial and metabolic disorders – These are conditions you are born with, inherit or that affect your metabolic system.
- Diabetes – This autoimmune disorder affects the kidneys, pancreas and other organs.
- Glomerular diseases – These are diseases that affect the glomeruli, which strain fluid in the kidneys.
- Hypertensive nephrosclerosis – This means there is damage to the kidneys caused by high blood pressure.
- Malignant hypertension – This is an extremely high blood pressure that damages the organs.
- Polycystic kidney disease – This disease causes numerous cysts or growths on the kidneys.
- Renovascular and other vascular diseases – These diseases cause blockages or narrowing in the renal arteries or veins.
- Tubular and interstitial diseases – These diseases affect the portions of the kidney outside the glomerulus, a cluster of blood vessels that filter waste products from the blood.
- Temporary lack of kidney function – Your new kidney may not start working immediately and you may need dialysis until it resumes normal kidney function.
- Organ rejection – Your body may reject the donor organ and you may need medication to help your body accept the new kidney.
- Kidney failure – Your new kidney may fail after a number of years and you may need to have a second transplant or go back on dialysis.
- Cancer – Immunosuppressant medication taken after transplant may leave you more vulnerable to disease.
- Diabetes – Medications taken after a transplant can cause diabetes.
- Heart attack or stroke – A transplant puts you at a higher risk than a healthy person who hasn’t had a transplant, especially if you have high blood pressure, high cholesterol or diabetes.
Potential side effects of a kidney transplant may include:
- Narrowing of the artery leading to the kidney—also called renal artery stenosis
- Blood clots
- Weight gain
- High blood pressure
- Prior sensitization – high panel reactive antibodies
Type of transplant: Deceased donor has a higher rejection than a living transplant
Advanced age of the donor
Prolonged cold ischemia time
Positive B cell crossmatch
Recipient’s age: Younger recipients have more rejection than older ones
Recipient’s race: African American race greater than White race
Delayed Graft function
Previous episodes of rejections
Renal transplant rejection, as stated earlier, is an immunological response that leads to inflammation with specific pathological changes in the allograft, due to the recipient’s immune system recognizing the non-self (foreign) antigen in the allograft. There are different mechanisms postulated depending on the type of rejection, as follows:
Hyperacute rejection – It is related to preexisting circulating antibodies in the recipient’s blood against the donor antigen (usually ABO blood group or HLA antigen), which is present at the time of transplantation. These antibodies attack and destroy the transplanted organ as soon as or within a few hours after allograft is revascularized.
Acute T cell-mediated rejection – in which the recipient’s lymphocytes become activated by recognition of foreign [non-self] donor antigens in the transplanted organ by antigen-presenting cells (APC) through direct, semi-direct or indirect pathways, which leads to activation and infiltration of the T cells and damage to the allograft.
ABMR – It is related to antibodies against foreign [non-selfx] donor antigens, mainly HLA antigen, which leads to damage to the allograft through activation of the complement-dependent pathway as well as independent mechanisms recruiting NK cells, polymorphonuclear cells, platelets and macrophages to attack the allograft. These antibodies can be either preexisting at a low level before the transplant or synthesized de novo post-transplant.
Chronic rejection – it is related to both immune and nonimmune mediated factors. The primary risk factor for chronic rejection is non-compliance with immunosuppressive medication. It can be either chronic antibody-mediated rejection, which is mainly related to the presence of donor HLA-antigens donor Specific Antibody (DSA) or Chronic cellular rejection, which is uncommon.
Histopathology of Kidney Transplant
The standard way to detect rejection is a renal allograft biopsy, which serves to accurately grade the severity of rejection, differentiate between different types, and guide the treatment.
There are two major classifications for the histopathological diagnosis of renal allograft biopsy: the Banff classification system and the Cooperative Clinical Trials in Transplantation (CCTT). Later, both were incorporated into the Banff 97 classification, to standardize the histopathological diagnosis of renal allograft biopsy. Subsequently, Banff has had updates at regular intervals; the last one was in 2017.
When performing a kidney biopsy, it should have adequate tissue to give a definitive interpretation. Adequate core biopsy must contain ten glomeruli and two arteries and section thickness 3 to 4 microns (marginal if 7 to 10 glomeruli and one artery; unsatisfactory if less than seven glomeruli or no arteries).[rx]
The histological characteristics of each type of rejection are as follows:
- Hyperacute rejection – The transplanted kidney turns mottled, dusky, and black as soon as it revascularized. Severe endothelial injury, PMN infiltration, whispered thrombosis, ischemic tissue necrosis will appear on biopsy.
ABMR – Histological features of ABMR include: arteriolar fibrinoid necrosis, fibrin thrombi in glomerular capillaries, glomerulitis, and peritubular Capillaritis, interstitial hemorrhage. Also, the presence of peritubular Capillary linear staining for C4d, which is a degradation product of the complement pathway that binds covalently to the endothelium, is highly suggestive of ABMR.
Acute T Cell-Mediated Rejection – Characterized by diffuse lymphocytic infiltration in the tubule, interstitium of the kidney, and in severe cases, vessels of the allograft
Chronic rejection lesions – like interstitial fibrosis, tubular atrophy, vascular fibrous intimal thickening, glomerular basement membrane double contouring (transplant glomerulopathy), arteriolar hyalinosis, hyaline arteriolar thickening
Banff system uses scores to assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies. It focuses mostly, but not exclusively, on the diagnostic features seen in rejection. According to the scoring of the various lesions described above, the staging is as below.
Category 1 – Normal biopsy or nonspecific changes
Category 2 – Antibody-mediated rejection – AMR: depending on the features of lesion further divided into acute AMR, chronic AMR active chronic AMR
Category 3 – Suspicious (borderline) for acute T cell-mediated rejection – TCMR.
Category 4 – TCMR. Depending on the score of chronic lesions, it further divides into acute TCMR, chronic TCMR, acute, chronic TCMR
Category 5 – Interstitial fibrosis and tubular atrophy – IFTA
Category 6 – Other changes not considered to be the result of acute or chronic rejection[rx]
Indications of Kidney Transplant
The indication for kidney transplantation is end-stage renal disease (ESRD), regardless of the primary cause.
- This is defined as a glomerular filtration rate below 15 ml/min/1.73 m2. Common diseases leading to ESRD include renovascular disease, infection, diabetes mellitus, and autoimmune conditions such as chronic glomerulonephritis and lupus; genetic causes include polycystic kidney disease, and a number of inborn errors of metabolism. The commonest ’cause’ is idiopathic (ie unknown).
- Diabetes is the most common known cause of kidney transplantation, accounting for approximately 25% of those in the United States. The majority of renal transplant recipients are on dialysis (peritoneal dialysis or hemodialysis) at the time of transplantation.
- However, individuals with chronic kidney disease who have a living donor available may undergo pre-emptive transplantation before dialysis is needed. If a patient is put on the waiting list for a deceased donor transplant early enough, this may also occur pre-dialysis.
- No longer need dialysis as long as kidney functions adequately
- Blood pressure is often easier to manage, but may still require medication
- Long-term follow-up care is less time-consuming than dialysis
- Fluid and dietary restrictions are usually no longer necessary
- May return to work
- Improved quality of life with expected increase in lifespan
- More cost-effective than dialysis
- Having a transplant means that you do not have to dialyse.
- You might find you have more energy, making you feel better able to cope with everyday life, including work or studies.
- Your sex life and fertility will probably improve (if it has been affected by CKD).
- If you have Type 1 diabetes and have a kidney and pancreas transplant you should no longer need to take insulin or tablets to control your blood sugar.
- You will not need to travel to the hospital for dialysis. However, you will need to come to the hospital for regular clinic appointments for up to six months after your transplant. After this time you will need to come to the clinic around three to four times a year depending on your needs.
- You will have a less restrictive diet than if you are on dialysis, although you will need to follow a low fat diet after a transplant.
- You do not need space at home to store equipment.
- You will be able to restart any sport or exercise after the transplant, although if you play contact sports please discuss this with your kidney doctor or nurse first. You must be a healthy weight for the operation so exercise is important while you are waiting for a transplant.
Contraindications of Kidney Transplant
Contraindications include both cardiac and pulmonary insufficiency, as well as hepatic disease and some cancers. Concurrent tobacco use and morbid obesity are also among the indicators putting a patient at a higher risk for surgical complications.
- Kidney transplant requirements vary from program to program and country to country. Many programs place limits on age (e.g. the person must be under a certain age to enter the waiting list) and require that one must be in good health (aside from the kidney disease).
- Significant cardiovascular disease, incurable terminal infectious diseases and cancer are often transplanted exclusion criteria. In addition, candidates are typically screened to determine if they will be compliant with their medications, which is essential for survival of the transplant. People with mental illness and/or significant on-going substance abuse issues may be excluded.
- HIV was at one point considered to be a complete contraindication to transplantation. There was fear that immunosuppressing someone with a depleted immune system would result in the progression of the disease. However, some research seems to suggest that immunosuppressive drugs and antiretrovirals may work synergistically to help both HIV viral loads/CD4 cell counts and prevent active rejection.
- Risks involved from general anesthesia as with any major operation
- Addition of immunosuppressive medication (and possible side effects) to your current medicines
- Need for continued care by a kidney specialist. Your kidney function and response to the medications must be medically managed for a healthy, long-term outcome.
- Transplantation is a treatment not a cure for the underlying cause of your kidney failure.
Diagnosis of Kidney Transplant
The approach for elevated serum creatinine in a renal transplant recipient would be the same as evaluating for AKI with added workup for the rejection.
The specific workup for evaluating allograft dysfunction should include the following[rx]:
- Blood type testing – A test to determine what type of blood—O, A, B, or AB—you have, and whether your blood is compatible with the potential donor’s blood. Type O is the most common blood type and is considered a universal donor, meaning someone who has this type of blood can donate to any other blood type. Type AB is considered a universal recipient and can receive blood from people of any blood type. Between the different types of blood, there are some that can and cannot give and receive one another. This test will determine blood type compatibility with your donor.
- Serum crossmatching – A test involving the mixing of your blood with that of the kidney donor to determine whether your body’s cells will attack the donor’s cells. If this happens, it means you have antibodies against this donor’s cells, and the crossmatch is considered “positive,” an indication that your body would reject a kidney from this donor. If your body does not produce antibodies against the donor’s cells, the crossmatch is “negative,” meaning your body will likely accept the donor organ and cells. For a kidney transplant, you will need a negative crossmatch in order to proceed.
- HLA (human leukocyte antigen) testing – A blood test that determines which antigens you (and the potential donor) have inherited. Antigens are proteins found on the cells and they are what trigger the body to produce antibodies, which fight off bacteria, viruses, and anything perceived as foreign to the body. While there are many different types of antigens, there are six that have been identified as particularly important for successful kidney transplant. This test will help determine whether your HLA is likely to fight against (reject) your donor’s HLA.
- Mental health evaluation. Psychological and social issues involved in organ transplantation, such as stress, financial issues, and support by family and/or significant others are assessed. These issues can greatly affect the outcome of a transplant. The same kind of evaluation is done for a living donor.
- Blood tests. Blood tests are done to help find a good donor match, to check your priority on the donor list, and to help the chances that the donor organ will not be rejected.
- Diagnostic tests. Diagnostic tests may be done to check your kidneys as well as your overall health status. These tests may include X-rays, ultrasound, kidney biopsy, and dental exams. Women may get a Pap test, gynecology evaluation, and a mammogram.
Rule out prerenal causes – Check orthostatic vital sign, blood pressure, and volume status
Rule out post-renal – causes mainly obstructive uropathy in older adults by bladder scan, renal US
CBC – Look for anemia and thrombocytopenia to rule out TMA
- Serum Creatinine – This blood test measures kidney function. It is checked each day while you are in hospital.
- Renal Scan – This test monitors blood flow to the kidney and kidney function.
- Renal Ultrasound – This test checks the kidney for any blockages or fluid collections around the kidney.
- Kidney Biopsy – This test is used to check for rejection.
Electrolyte abnormality – related to CKD, AKI
UA and urine culture – It is essential to rule out infection as a cause of AKI
Check for proteinuria – Either UPCR or 24-hour urine collection as nephrotic range proteinuria correlates with the presence of extensive transplant glomerulopathy
Check BK Virus, CMV PCR – in clinically indicated patients
Testing for donor-specific antibodies
Transplant renal ultrasound with doppler for renal arterial and venous indices
Many transplant centers use testing for donor-derived free DNA testing. This test can be positive even before the actual rise in serum creatinine, suggesting possible rejection.
While dealing with renal allograft dysfunction, equal weight should be given to find out the possible etiologies other than the rejection.
The following are the most common reasons for allograft dysfunctions other than the allograft rejection.[rx]
A. Immediate Post Transplant (less than one week):
- Postischemic acute tubular necrosis or Ischemia-reperfusion injury.
- Volume depletion leading to pre-renal AKI
3. Surgical complications:
Fluid collection – urinoma, perinephric hematoma or lymphocele
Vascular thrombosis – arterial and venous
Multiple renal arteries from the donor’s kidney – infarction of the part of the allograft or necrosis of the ureter leading to urinary obstruction or urinary leak.
Calcium oxalate crystals deposits in renal allograft
B. Early (1 week to 3 months) and Late Post Transplant (over three months)
- Volume depletion
- Acute tubular necrosis
- Calcineurin inhibitor nephrotoxicity – manifesting as acute azotemia as well as chronic progressive renal disease.
- Urinary obstruction
- Infections – Bacterial pyelonephritis andViral infections – BK ( polyomavirus) and CMV
- Acute and chronic interstitial nephritis
Recurrent primary glomerular diseases
Primary membranous nephropathy
Ig A nephropathy
De novo glomerular disease
In patients with a prior history of TTP, HUS, antiphospholipid antibody syndrome
Associated with calcineurin inhibitor nephrotoxicity
Transplant renal artery stenosis
Post-transplant lymphoproliferative disease
You have to meet certain criteria to be approved for a kidney transplant. You cannot have an active infection, cancer or severe circulatory problems involving your heart, brain or major blood vessels. You must be willing to take medications for the rest of your life to prevent your body from rejecting the new kidney.
You will need a thorough medical evaluation. This includes:
- A physical examination
- A chest X-ray
- An electrocardiogram (EKG)
- Blood tests to check for:
- Viral illnesses such as HIV, hepatitis, herpes simplex virus and cytomegalovirus
- Blood samples to check:
- Your blood type and tissue type to determine if a donor is a good match.
- Possible additional tests:
- Cardiac tests
- Screenings for certain types of cancer
If you smoke or have problems with substance abuse, you must complete a treatment program before you receive your new kidney.
While you prepare for your kidney transplant, you will meet regularly with a transplant team at the medical center where you will have your surgery. These professionals can offer you a wide range of support services during the pre-transplant period.
The transplant team usually includes:
- A doctor who specializes in kidney problems (a nephrologist)
- A transplant surgeon
- A social worker
If your kidney transplant will come from a living donor, you usually will be able to schedule the time of your transplant surgery. In most cases, your pre-transplant waiting period will be only a few weeks. During this time, your donor will have medical tests. These will ensure that he or she is strong enough to undergo surgery. Additional tests will confirm that the donor’s kidneys are functioning normally.
If you do not have a living kidney donor, your name will be placed on a waitlist for a kidney from a dead donor. This donor must be a good match for you. The average waiting time for a kidney from a dead donor is two to three years. While you are on the waiting list, the transplant team will evaluate your health periodically. You must have medical insurance that will cover the cost of a transplant or be able to pay for it yourself.
What happens during a kidney transplant?
A kidney transplant requires a stay in a hospital. Procedures may vary depending on your condition and your healthcare provider’s practices.
Generally, a kidney transplant follows this process:
- You will remove your clothing and put on a hospital gown.
- An intravenous (IV) line will be started in your arm or hand. More catheters may be put in your neck and wrist to monitor the status of your heart and blood pressure, and to take blood samples. Other sites for catheters include under the collarbone area and the groin blood vessels.
- If there is too much hair at the surgical site, it may be shaved off.
- A urinary catheter will be inserted into your bladder.
- You will be positioned on the operating table, lying on your back.
- Kidney transplant surgery will be done while you are asleep under general anesthesia. A tube will be inserted through your mouth into your lungs. The tube will be attached to a ventilator that will breathe for you during the procedure.
- The anesthesiologist will closely watch your heart rate, blood pressure, breathing, and blood oxygen level during the surgery.
- The skin over the surgical site will be cleansed with an antiseptic solution.
- The surgeon will make a long incision into the lower abdomen on one side. The surgeon will visually inspect the donor kidney before implanting it.
- The donor kidney will be placed into the belly. A left donor kidney will be implanted on your right side; a right donor kidney will be implanted on your left side. This allows the ureter to be accessed easily for connection to your bladder.
- The renal artery and vein of the donor kidney will be sewn to the external iliac artery and vein.
- After the artery and vein are attached, the blood flow through these vessels will be checked for bleeding at the suture lines.
- The donor ureter (the tube that drains urine from the kidney) will be connected to your bladder.
- The incision will be closed with stitches or surgical staples.
- A drain may be placed in the incision site to reduce swelling.
- A sterile bandage or dressing will be applied.
Talk with your healthcare provider about what you will go through during your kidney transplant.
Treatment of Kidney Transplant
The treatment plan determination uses multiple factors, including the type of rejection, the severity of the histological lesion, the chronicity score, and the recipient comorbidity. So what will be discussed is a general guideline, but tailoring medical treatment of individual characteristics is needed.[rx][rx]
1. Hyperacute rejection
No effective therapy usually leads to early allograft nephrectomy, and so prevention is the key by assuring through the following
i) ABO-compatibility between donor and recipient. Sometimes, it is advisable to address ABO incompatibility under specific criteria, and careful pre-transplant preparation of recipient with the removal of anti-ABO antibodies by plasmapheresis is an option, IVIG with or without rituximab
ii) Pre-transplant cross-match [complement cell cytotoxicity test]: Recipient serum is added to donor lymphocytes. If the test is positive (which means the recipient has an antibody that reacts with the donor HLA antigens on lymphocyte), one should not proceed with transplant unless these antibodies are removable pre-transplant.
2. Antibody-Mediated Rejection
The treatment of acute antibody-mediated rejection also depends on the level of the antibody levels. Higher antibody levels need plasma exchange for the removal of the antibodies. The following are the different modalities used for AMR:
i) Plasma Exchange: 3 to 5 sessions daily on every other day is used for antibody removal followed by IVIG and rituximab
ii) IVIG: IV immunoglobulin (100 to 200 mg/kg) is used followed by the last session of plasma exchange when used in combination with plasmapheresis or higher dose 2g/kg after the final session of plasmapheresis.
iii) Rituximab: Anti CD20 cell antibody rituximab (375 mg/m^2) is used in combination with IVIG followed by plasma exchange
iv) Bortezomib: Plasma cell inhibitor bortezomib (1.3 mg/m^2) is also used in combination with plasma exchange and IVIG
v) Splenectomy: Splenectomy is very rarely an option, but there are anecdotal reports of successful treatment of refractory rejections
vi) Optimize the dose and the level of the maintenance immunosuppressive drugs.
3. T Cell-Mediated rejection
They receive treatment with the following agents based on the severity of the lesion.
i) Methyl Prednisone IV (250 to 1000 mg daily) targeting T cells, B cells, and macrophages; given for 3 to 5 days
ii) rATG – Rabit anti-thymocyte globulin IV (1 to 1.5 mg/kg) targeting T cell receptors. The duration varies among different transplant centers, but in general, it is for 7 to 14 doses based on the response and Cd3 level.
iii) Optimize the dose and the level of the maintenance immunosuppressive drugs.
4. Chronic rejection
Since the antibody-mediated rejection mechanism is a major cause of chronic rejection, the same therapy as ABMR has been used, but generally, these measures are ineffective when Scr is over 3 mg/dl and/or heavy proteinuria.
Anti-rejection medications, also known as immunosuppressive agents, help to prevent and treat rejection. They are necessary for the “lifetime” of the transplant. If these medications are stopped, rejection may occur and the kidney transplant will fail.
Below is a list of medications that might be used after a kidney transplant. A combination of these drugs will be prescribed dependent on the specific transplant needs.
Prednisone is taken orally or intravenously. Most side effects of prednisone are related to drug dosage levels. Prednisone is used at low dosages to minimize side effects. The possible side effects of prednisone are:
- Changes in physical appearance such as puffiness of the face and weight gain.
- Irritation to the stomach lining.
- Increased risk of bruising and decreased rate of healing.
- Increased sugar level in the blood (steroid-induced diabetes).
- Unexplained mood changes. This may mean depression, irritability, or high spirits.
- General muscle weakness or pain in knees or joints.
- Formation of cataracts. A clouding of the lens of the eye occurs infrequently with long-term use of prednisone.
Azathioprine (Imuran®) is taken orally or intravenously. The most common side effects associated with azathioprine are:
- Thinning of hair
- Irritation of the liver
- Decreased white blood cell count
Mycophenolate mofetil – Although most centers still use treatments based on steroids and ciclosporin, tacrolimus and mycophenolate mofetil have emerged as effective and well-tolerated options for inducing and maintaining immunosuppression.[rx] Mycophenolate mofetil (CellCept) is taken orally. The most common side effects of mycophenolate mofetil are:
- Abdominal aches and/or diarrhea
- Decreased white blood cell count
- Decreased red blood cell count
Mycophenolate sodium – is taken orally. It provides the same active ingredient as mycophenolate mofetil and generally has the same side effect profile. It is enterically coated to potentially reduce abdominal aches and diarrhea.
Sirolimus (Rapamune) is taken orally. The most common side effects of sirolimus are:
- Decreased platelet count
- Decreased white blood cell count
- Decreased red blood cell count
- Elevated cholesterol and triglycerides
Cyclosporine (Neoral, Gengraf) is taken orally. The most common side effects of cyclosporine therapy are:
- Kidney dysfunction
- Irritation of the liver
- Excessive body hair growth
- High blood pressure
- Swollen/bleeding gums
- High potassium in the blood
- Increased sugar level in the blood (drug-induced diabetes)
(Prograf) is taken orally. The most common side effects of tacrolimus therapy are:
- Kidney dysfunction
- High blood pressure
- High potassium in the blood
- Increased sugar level in the blood (drug-induced diabetes)
Antithymocyte globulin (Thymoglobulin®) is given intravenously. Thymoglobulin can cause:
- Decreased white blood cell and platelet counts
It is given intravenously and can cause
- Shortness of breath
Anti-interleukin 2 receptor antibodies
Another major advance in the area of induction immunosuppression is the development of the anti-interleukin 2 receptor antibodies (basiliximab and daclizumab). These drugs have produced impressive reductions in the rates of early rejection in adult and paediatric transplants [rx] Once again, cost issues have restricted the use of these promising drugs.
Anti-interleukin-2 Receptor Antibody (Zenapax or Simulect) These two drugs are given intravenously. These medications rarely cause side effects but can include:
- Allergic reaction
- Shortness of breath
- Decreased white blood cell counts
Sirolimus is another immunosuppressant that has entered the clinical arena in the United States and, more recently, in Europe. Impressive reductions in the rates of early rejection and hypertension with sirolimus compared with alternative agents need to be balanced against adverse changes in lipid profiles and a lack of data on long term outcome.[rx]
Almost 20 years after ciclosporin’s introduction, clinicians are still learning how to use this drug. Recent studies have shown that it is better to adjust the dose of ciclosporin according to blood levels two hours after treatment (C2 monitoring) than trough levels. Preliminary data show that this new technique produces reductions in rejection rates and side effects.[rx] The advantage of this technique needs to be compared with the claims of alternative immunosuppressive agents.
- Minimization refers to lowering target blood trough levels of CNIs, with or without another immunosuppressive agent. A systematic review and meta-analysis showed that CNI minimization was associated with a relatively low risk of AR and overall improved allograft function.[rx] The timing of CNI minimization was also studied. CNI minimization during the first six months post-transplant reduced the incidence of rejection compared to reducing CNI doses in the second 6 months post-transplant. No head to head trials, however, were conducted to compare early and late minimization directly.
- Combining low dose CNI with mycophenolic acid (MPA) preparations also reduced the risk of AR with no difference in mortality. Pairing CNI minimization with a mammalian target of rapamycin (mTOR) inhibitor (such as sirolimus or everolimus) did not increase the risk of biopsy-proven AR. It led to an improvement in kidney function in some studies. It is worth noting. However, that full dose CNI plus mTOR inhibitor therapy increases the risk of nephrotoxicity.
- Conversion refers to switching CNI to another maintenance drug. Converting from CNI to an mTOR inhibitor showed improvement in kidney function, which was more observed with the conversion from Cyclosporine compared to Tacrolimus.[rx] Conversion to an mTOR inhibitor was also associated with a lower risk of cytomegalovirus (CMV) infection.[rx]
- Conversion to Sirolimus showed better outcomes in patients with GFR exceeding 40 ml/min with less proteinuria, suggesting that conversion should occur before significant parenchymal damage.[rx] Grimbert et al. suggested that early conversion to mTOR inhibitors within one year was associated with increased production of dnDSA, which increased the risk of antibody-mediated rejection.
- Withdrawal refers to tapering CNIs until completely discontinued. CNI withdrawal with either MPA or mTOR inhibitor-based regimens was associated with an increased risk of rejection. Early withdrawal (<6 months post-transplant) was associated with an increased risk of graft loss, with insufficient evidence for both rejection and a decrease in renal function. Late withdrawal with the continuation of MPA preparations was associated with an overall greater risk of rejection.[rx] CNI withdrawal from Azathioprine based regimens was also associated with increased rejection.[rx]
- Avoidance refers to CNI free regimens planned from the start. Initial trials to avoid CNIs while using Daclizumab or anti-thymocyte globulin were associated with an increased risk of AR, which required reintroduction of CNIs in some patients.[rx] Sirolimus based immunosuppression regimens were also compared to CNI based regimens. Comparing Sirolimus to Tacrolimus in MPA based regimens showed an increased risk of graft loss. Sirolimus, however, was associated with improved kidney function and reduced risk of CMV infection.[rx]
- A novel fusion protein that inhibits T cell activation, was also compared to CNI based regimens. Vincenti et al. randomized patients into three groups; a Cyclosporine, an intensive Belatacept, and a less intensive Belatacept based regimen. Patients were followed for seven years.
- Patients on Belatacept based regimens showed a 43% reduction in risk of graft loss and death, compared to cyclosporine. Kidney function improved in both belatacept based regimens, while it declined with cyclosporine.[rx]
Who is on my transplant team?
A successful transplant involves working closely with your transplant team. Members of the team include:
- You—you are an important part of your transplant team.
- Your family members – this may include your spouse, parents, children, or any other family member you would like to involve.
- Transplant surgeon – the doctor who places the kidney in your body.
- Nephrologist – a doctor who specializes in kidney health and may work closely with a nurse practitioner or a physician’s assistant.
- Transplant coordinator – a specially trained nurse who will be your point of contact, arrange your appointments, and teach you what to do before and after the transplant.
- Pharmacist – a person who tells you about all your medicines, fills your prescriptions and helps you avoid unsafe medicine combinations and side effects.
- Social worker – a person trained to help you solve problems in your daily life and coordinate care needs after your transplant.
- Dietitian – an expert in food and nutrition who teaches you about the foods you should eat and avoid, and how to plan healthy meals.
Your transplant team will be able to provide the support and encouragement you need throughout the transplant process.
What happens after a Renal Transplantation?
In the hospital
- After the surgery, you will be taken to the recovery room. Once your blood pressure, pulse, and breathing are stable and you are alert, you may be taken to the intensive care unit (ICU) for close monitoring. In time, you will be moved out of the ICU to a regular nursing unit as you recover and you are closer to going home. Kidney transplant usually calls for several days in the hospital.
- A kidney from a living donor may start to make urine right away. Urine production in a cadaver kidney may take longer. You may need to continue dialysis until urine output is normal.
- You will have a catheter in your bladder to drain your urine. The amount of urine will be measured to check how the new kidney is working.
- You will get IV fluids until you are able to eat and drink enough on your own.
- Your team will closely watch how your antirejection medicines are working to make sure you are getting the best dose and the best combination of medicines.
- Blood samples will be taken often to check the status of the new kidney, as well as other body functions, such as the liver, lungs, and blood system.
- You will slowly move from liquids to more solid foods as tolerated. Your fluids may be limited until the new kidney is working fully.
- Usually, by the day after the procedure, you may start moving around. You should get out of bed and move around several times a day.
- Take a pain reliever for soreness as advised by your healthcare provider. Avoid aspirin or certain other pain medicines that may increase the chance of bleeding. Be sure to take only recommended medicines.
Nurses, pharmacists, dietitians, physical therapists, and other members of the transplant team will teach you how to take care of yourself once you are discharged from the hospital including care for your incisions.
- You will be ready to go home when your vital signs are stable, the new kidney is working, and you do not need constant hospital care.
- Once you are home, it is important to keep the surgical area clean and dry. Your healthcare provider will give you specific bathing instructions. Generally, the incision should not be submerged in water until the skin heals as this increases the risk for infection. The stitches or surgical staples will be removed during a follow-up office visit.
- You should not drive until your healthcare provider tells you it’s OK. Plan to have someone drive you home from the hospital and to your follow-up appointments.
- Avoid any activity or position that causes pressure to be placed on the new kidney. Other activity restrictions may apply.
- Check your blood pressure and weight at home every day. Increases in these may mean your kidneys are not filtering fluid properly. You need to be seen by your transplant team promptly.
Tell your healthcare provider if you have
- Fever, which may be a sign of rejection or infection
- Redness, swelling, or bleeding or another drainage from the incision site
- Increase in pain around the incision site, which may be a sign of rejection or infection
Fever and tenderness over the kidney are some of the most common symptoms of rejection. A rise in your blood creatinine level (blood test to measure kidney function) and/or blood pressure may also suggest rejection.
When to Call the Transplant Team
You should call the Transplant Team if you experience any of these symptoms, or any time anything about your health changes, even if it is not related to your transplant:
- The temperature of 100°F or greater
- Blood pressure greater than 170/100 for two readings in a row
- Weight gain of more than three pounds in a day or five to seven pounds in a week
- Cough, shortness of breath, sore throat, chills
- Nausea, vomiting or stomach pain
- Decreased appetite
- Blood in the urine or bowel movements, painful urination
- Increased pain, redness, or pus-like drainage at the incision
- Pain, tenderness or swelling in the area of the new kidney
- Feeling unusually tired
- Persistent headache or flu-like symptoms
- Any unexplained rash, sores, or bruising
- Swelling of the hands, feet or ankles
- Inability to take medications for any reason
- Anything that concerns you about your health
LifeStyle After Renal Transplantation
If you smoke, it’s strongly recommended that you stop as soon as possible because smoking can reduce the life of your new kidney and can increase your risk of developing some types of cancer.
The NHS Smokefree website can provide support and advice to help you stop, and your GP can also recommend and prescribe treatments that can help. Read more about stopping smoking.
Most people are able to enjoy a much more varied diet after a kidney transplant, although you may be advised to avoid some foods after the operation until the kidney is working properly. During the early stages after a transplant, while you’re on higher doses of immunosuppressant medication (see below), you should avoid eating foods that carry a high risk of food poisoning, including:
- unpasteurized cheese, milk or yogurt
- foods containing raw eggs (such as mayonnaise)
- undercooked or raw meats, fish and shellfish
Once your kidney is working properly and the best immunosuppressant dose for you has been identified, you’ll usually be advised to follow a generally healthy diet, as this can reduce your risk of complications such as diabetes.
A healthy diet should include:
- at least 5 portions of fruit and veg a day
- plenty of potatoes, bread, rice, pasta and other starchy foods; ideally you should choose wholegrain varieties
- some milk and dairy foods
- some meat, fish, eggs, beans and pulses, and other non-dairy sources of protein
Avoid food that contains high levels of salt, as salt can cause high blood pressure, which can be dangerous for people with a kidney transplant. See facts about salt for more information and advice.
Exercise and weight loss
Once you’ve started to recover from the effects of surgery, you should try to do regular physical activity.
Adults should do at least 150 minutes (2 hours and 30 minutes) of moderate-intensity exercise every week. This includes any activity that increases your heart and breathing rate – it may make you sweat, but you are still able to hold a normal conversation.
- fast walking
- riding a bike on level ground or with few hills
Choose physical activities that you enjoy, as you’re more likely to continue doing them. It’s unrealistic to meet these exercise targets immediately if you have not exercised much in the past. You should aim to start gradually and then build on it. If you’re overweight or obese, you should try to achieve a healthy weight. This can be safely done through a combination of eating a healthy, calorie-controlled diet and regular exercise. Aim for a body mass index (BMI) of 18.5 to 25.
Alcohol, drugs and medications
Regularly drinking alcohol above the maximum recommended limits can raise your blood pressure, which can be dangerous for people with a kidney transplant. To keep your risk of alcohol-related harm low, the NHS recommends:
- not regularly drinking more than 14 units of alcohol a week
- spread your drinking over 3 days or more if you drink as much as 14 units a week
- it’s a good idea to have several alcohol-free days each week
Read more about alcohol units and get tips on cutting down your alcohol consumption. Alcohol is also high in calories, so you’ll gain weight if you drink regularly. Being overweight will also increase your blood pressure. Read more about the calories in alcohol.
You should also avoid taking any illegal drugs after a kidney transplant, as they can damage your kidneys, cause a sudden rise in blood pressure, and react unpredictably with your immunosuppressant medications. Finally, always check with your care team before taking any medication, including over-the-counter medicines and herbal remedies such as St John’s wort. Some medications could be potentially harmful if you have had a kidney transplant and are taking immunosuppressant medication.
Immunosuppressants and infection
If you have a kidney transplant, you’ll usually need to take immunosuppressant medications for the rest of your life to prevent your body’s immune system from attacking the new kidney. Widely used immunosuppressants include tacrolimus, ciclosporin, azathioprine, mycophenolate, prednisolone and sirolimus.
However, taking immunosuppressive medications on a long-term basis will weaken your immune system and make you more vulnerable to infections, so you’ll need to take extra precautions against infection:
- avoid contact with people you know currently have infections, such as chickenpox or flu
- practice good personal hygiene – wash your hands regularly with soap and hot water, particularly after going to the toilet and before preparing food and eating meals
- if you cut or graze your skin, clean the area thoroughly with warm water, dry it, then cover it with a sterile dressing
- Make sure your vaccinations are up to date, although you won’t be able to have any vaccines that contain live viruses, such as measles, mumps, and rubella (MMR) vaccine.
When to get medical advice
If you think you may have an infection, contact your GP or transplant center for advice. Prompt treatment may be required to prevent serious complications from developing.
Symptoms of the infection can include:
- a high temperature of 38C or above
- feeling hot and shivery
- aching muscles
Complications of kidney transplant
- risks related to the procedure itself
- risks related to the use of immunosuppressant medications (which reduce the activity of your immune system)
- risks related to something going wrong with the transplanted kidney
Most complications occur in the first few months after a transplant, but can develop after many years. Some of the main short-term and long-term complications of a kidney transplant are outlined below.
- Minor infections, such as urinary tract infections (UTIs), colds and flu, are common after kidney transplants.
- Potentially more serious infections, such as pneumonia and cytomegalovirus (CMV), can occur and may require hospital treatment.
- Blood clots can develop in the arteries that have been connected to the donated kidney. This is estimated to occur in around 1 in 100 kidney transplants.
- In some cases, it may be possible to dissolve the blood clots using medication, but it’s often necessary to remove the donated kidney if the blood supply is blocked.
Narrowing of an artery
- Narrowing of the artery connected to the donated kidney, known as arterial stenosis, can sometimes occur after a kidney transplant. In some cases, it can develop months, or even years, after the transplant.
- Arterial stenosis can cause a rise in blood pressure. The artery often needs to be stretched to widen it, and a small metal tube called a stent may be placed inside the affected artery to stop it narrowing again.
- The ureter (the tube that carries urine from the kidney to the bladder) can become blocked after a kidney transplant. It can be blocked soon after the transplant – by blood clots, for example. It can also be blocked months or years later, usually due to scar tissue.
- It may be possible to unblock the ureter by draining it with a small tube called a catheter. Sometimes surgery may be required to unblock the ureter.
- Occasionally, urine may leak from where the ureter joins the bladder after surgery. This usually occurs during the first month after the procedure. The fluid may build up in the tummy or leak through the surgical incision.
- If you develop a urine leak, you’ll usually need to have further surgery to repair it.
- Acute rejection means the immune system suddenly begins to attack the donated kidney because it recognises it as foreign tissue.
- Despite the use of immunosuppressants, acute rejection is a common complication in the first year after a transplant, affecting up to 1 in 3 people.
- In many cases, acute rejection does not cause noticeable symptoms and is only detected by a blood test. If it does occur, it can often be successfully treated with a short course of more powerful immunosuppressants.
Immunosuppressant side effects
Immunosuppressants prevent your body’s immune system from attacking the new kidney, which would cause the transplanted kidney to be rejected. A combination of 2 or 3 different immunosuppressants is usually taken long term.
These can cause a wide range of side effects, including:
- an increased risk of infections
- an increased risk of diabetes
- high blood pressure
- weight gain
- abdominal pain
- extra hair growth or hair loss
- swollen gums
- bruising or bleeding more easily
- thinning of the bones
- mood swings
- an increased risk of certain types of cancer, particularly skin cancer
The doctor in charge of your care will be trying to find the right dose that is high enough to “dampen” the immune system to stop rejection, but low enough that you experience very few or no side effects.
Finding the optimal dose to achieve both goals is often a difficult balancing act. It may take several months to find the most effective dose that causes the least amount of side effects.
Diabetes is a common complication of having a kidney transplant. Diabetes is a lifelong condition that causes a person’s blood sugar level to become too high. Some people develop it after a kidney transplant because, as they no longer feel unwell, they eat more and gain too much weight. Some types of immunosuppressants can also make you more likely to develop diabetes.
Symptoms of diabetes include:
- feeling very thirsty
- going to the toilet to urinate a lot, especially at night
Diabetes can often be controlled using a combination of lifestyle changes, such as alterations to your diet, and medication.
High blood pressure
High blood pressure is also a common long-term complication of a kidney transplant.
- Many people who need a kidney transplant already have an increased risk of developing high blood pressure, and taking immunosuppressants can make the condition worse.
- High blood pressure doesn’t usually cause any noticeable symptoms, but it can increase your risk of developing other serious conditions, such as heart disease, heart attacks and strokes.
- Because of the risk of high blood pressure, you’ll have your blood pressure checked at your follow-up appointments. You can also check your own blood pressure at home with a simple device available from most pharmacies. Read more about testing your blood pressure.
The long-term use of immunosuppressants also increases your risk of developing some types of cancer, particularly types known to be caused by viruses (as you will be more vulnerable to the effects of infection).
- Most types of skin cancer – including melanoma and non-melanoma
- Kaposi’s sarcoma – a type of cancer that can affect both skin and internal organs
- Lymphoma – a cancer of the lymphatic system
You can reduce your risk of skin cancer by avoiding exposure to the sun during the hottest part of the day and by applying sun cream to your lips and all exposed areas of your skin every day.
The costs of a kidney transplant include the transplant evaluation, testing, surgery, follow-up care, and medication.
These costs are variable and depend on the patient’s recovery and time spent in the hospital. Other costs associated with transplantation include:
- Extensive lab tests
- Fees for transplant surgeons and operating room personnel
- Organ recovery
- Lodging and food for family members while the patient is hospitalized
- Physical therapy and rehabilitation
- Anti-rejection drugs and other medications (monthly estimated cost is approximately $3,000 immediately following transplant)
According to the United Network for Organ Sharing (UNOS), the first-year billed charges for a kidney transplant are usually more than $262,000.
[bg_collapse view=”button-orange” color=”#4a4949″ expand_text=”Show More” collapse_text=”Show Less” ]