Kidney transplantation

In 2021 approximately 91,000 patients were awaiting kidney transplantion..

Patients with end-stage kidney failure on dialysis have a 10 fold improved survival after renal transplantation, and have a substantially better quality of life than those patients who remain on dialysis.

Patients who received renal transplants have a 68% lower mortality rate in patients eligible for transplant who continue to receive hemodialysis.

Fewer than 15% of patients who initiated hemodialysis are placed on a deceased donor kidney transplantation waiting list or receive a kidney transplant within one year of dialysis initiation.

Kidney transplantation improves quality-of-life, and is less costly in the long run compared with dialysis treatments.

Approximately 20% of the US kidney waiting list is made up of candidates whose allografts have failed.

Factors that contribute to low kidney transplantation rates include: low organ donation rates, organ allocation system goals, patient factors, physician factors, and healthcare organization barriers.

Patients who have a renal transplant average 1 hospital admission per year.

Survival for kidney transplantation has improved despite increases in the recipients age, BMI, frequency of diabetes, and length of time undergoing dialysis, as well as a higher proportion of recipients with previous kidney transplant.
Survival for kidney transplantation  has improved, despite increases in donor age, reactive antibody levels, HLA mismatches, and despite prior transplantation in the recipient.
Improve kidney transplantation  survival has been observed among older and frailer recipients, as well as those with diabetes and obesity.
Five year graft survival rates in the US for primary kidney transplants from the from deceased donors and living donors with 72% and 85%, respectively: compared with 81% and 90% in Australia and New Zealand, 79% and 87% in Europe, and 81% and 91% in Canada.

European recipients of deceased donors transplants have higher five year and 10 year graft survival rates.

Lymphocyte depletion with antithymocyte globulin or alemtuzumab reduces acute n episodes but is associated with. rejection cytomegalovirus reactivation and posttransplant lymphoproliferative disease. 

Short and long-term patient and graft survival rates are better after living vs. cadaver donor transplants.

Kidney transplantation as a treatment for ESRD offers a better quality of life, and on average 10 extra years of life for recipients of the first deceased donor kidney transplant compared with treatment with dialysis (Wolfe RA et al).

Rates of graft loss and acute rejection are higher in blacks than in white recipients, especially among younger patients.

Survival rates for kidney grafts from living donors superior to those from cadaveric donors at 1, 5, and 10 years, but at 10 years the survival rate for living donor grafts is down to 55%.

One-year kidney transplant graft survival is consistently better for recipients of living donor (96.8%) versus deceased donor kidney transplants (92%).

Overall there has been improvement and long-term outcomes related to a decline in rates of acute rejection, better pre-transplantation cross matching, prudent use of paired exchange transplants for candidates for incompatible living donors, surveillance for viral infection, and effective antiviral prophylaxis.
The major causes of transplant failure, excluding death, are: alloimmune injury and recurrent glomerulonephritis.
Patients sensitized to HLA as a result of blood transfusion, pregnancy, previous transplantation increase likelihood of donor specific anti-HLA antibodies, which have been associated with hyperacute rejection, antibiotics mediated rejection, high rates of organ loss and is considered a contraindication to transplantation.
During the first year after  transplantation ,most graft losses are due to technical issues and vascular complications, followed by acute rejection and glomerulonephritis.
Acute rejection, is typically confirmed by kidney biopsy and is common in kidney transplantation.
Acute rejection may be  T cell mediated, antibody-mediated, or both, and are graded on the basis of the Banff classification.
Acute rejection in the first year is primarily a T cell mediated rejection, with fewer cases of antibody mediated rejection.
Early antibody mediated rejection is treated with glucocorticoids, plasmapheresis, and intravenous immunoglobulin.
Late antibody mediated rejection may be treated by augmenting maintenance immuno suppressive therapy, but the use of other therapies remains questionable.
After the first year acute rejection is often a combination of antibody mediated and T cell mediated rejection.
T cell mediated rejection is revealed by histologic evidence of capillaritis within combination of inflammatory cells in graft capillaries, the presence of complement fraction C4d in peritubular capillaries, and circulating donor specific antibodies against donor HLA antigens.
Acute rejection is the result of sub optimal immuno suppressive therapy, particularly in transplant recipients at high immunologic risk, nonadherence to immuno suppressive therapy, or a reduction in immunosuppressive medication is because of infections or cancers.
The primary causes of death with a functioning graft during the first year after transplantation are cardiovascular disease, infection, and cancer.
Cancer is the leading cause of death in kidney transplant recipients with an incidence of up to three times higher than the general population.
The cancer risk is associated with duration and dose of immunosuppression therapy.
After the first year, the primary causes of death or cancer, cardiovascular disease, and infection.

Improved outcomes for living donor kidney transplantation include: the time from an initiation of dialysis to transplant surgery is usually shorter, surgery can be scheduled elective.y, there is no kidney damage from donor death.

Delayed graft function is experienced only by 4% of living donor kidney recipients Versus 24% for recipients of deceased donor kidneys.

From HLA-identical living donors are expected to have a survival rate of 70-75% at 10 years.

Currently 34% of kidneys that are now transplanted come from unrelated donors.

Transplantation from living donors is the predominant approach today.

Majority of kidney transplants are from deceased heart beating donors.

With brain death the kidney is exposed to cytokines causing a inflammatory state.

Prolonged cold storage and reperfusion injury cause renal injury to a transplanted kidney.

The average cold time for deceased donor kidneys is 20-30 hours versus 20 minutes with living donor kidneys, which leads to more deceased donor cold ischemic injury.

Associated with a delayed graft function and acute rejection have a greater incidence of chronic dysfunction during cold storage.

Use of dopamine and norepinephrine during donor care is associated with fewer acute rejections and superior long-term graft survival (Schnuelle P).

Use of donor dopamine associated with reduced use of dialysis after transplantation.

Dopamine stimulates specific receptors and protects endothelial cells from oxidative stress .

Use of dopamine in donors delays hypothermia mediated cell death, ADP depletion and accumulation of intracellular calcium ions.

In a randomized control study of 264 deceased heart beating kidney donors to receive low dose dopamine (4microgm/kg/min) it was indicated that recipients of the dopamine treated grafts require significantly less dialysis (Schnuelle P). Kidney transplantation-use of dopamine to improve use of post transplant dialysis is due to its ameliorating effects of accumulation of reactive oxygen species under cold storage conditions rather than stabilization of circulatory factors in the brain dead donor.

Up to 30% of recipients have one or more acute rejection episodes in the first 6 months after transplant.

Incidence of posttransplant lymphoproliferative disease in living donor recipients is less than 0.01%.

Kidney transplant rejection can be hyperacute, occurring within minutes, acute, occurring within days to weeks, chronic, occurring months to years after transplantation.

A combination of immunosuppressive drugs targeting T cells is required to prevent kidney rejection and graft loss.
Rabbit antithymocyte globulin and humanized anti-CD25 monoclonal antibody basiliximab are the most commonly used induction agents in the US.
Most transplant patient received a calcineurin Inhibitor such as cyclosporine or tacrolimus, typically in combination with an anti-metabolite such as azathioprine, mycophenolate mofetil, and a glucocorticoid.
Mycophenolate mofetil has largely replaced azathioprine, except in pregnancy when mycophenolate mofetil is contraindicated, or if there is G.I. intolerance to mycophenolate.
The use of targeted rapamycin, mTOR inhibitors sirolimus and everolimus remain limited.

Calcineurin and Inhibitors are highly effective in preventing acute kidney transplantation rejection but have inherent nephrotoxicity.

Kidney transplant rejection may be classified along pathophysiologic lines-cellular-interstitial, vascular, or antibody-endothelial.

Transplant rejection may be classified by severity histologic inflammation and injury-Banff schema.

Transplant rejection may be classified by presence or absence of glucocorticoid resistance.

Transplant rejection may be classified by the presence or absence of renal dysfunction.

Transplant rejection may be classified by immunologic mechanisms such as adaptive or innate immune system response.

Acute rejection and delayed graft function which can occur early in the posttransplant period negatively affect graft survival.

Acute rejection within one year after transplantation is now less than 15%.

Acute rejection episodes while less common than previously on more severe than the rates of graft survival beyond 5 years has remained the same(Meier-Kriesche HU et al).

Delay in graft function associated with an increased risk of acute rejection and graft survival is superior in individuals who do not either delayed graft function or acute rejection.

Up to 40% of transplant recipients may have sub clinical inflammation, which falls below the threshold for diagnosis of rejection.

Acute rejection negatively affects long-term survival, depending upon the severity, persistence, and histologic type of rejection.

Acute rejection that occurs more than three months after the transplantation has a worse prognosis than acute rejection occurring earlier.

Subclinical inflammation has a deleterious effect on the outcome of transplantation.

Delayed graft function is defined as the requirement for dialysis in the recipient within seven days after receiving a renal transplant.

Delayed graft function results in increased healthcare costs and decreases long-term graft function.

Delayed graft function is reported in up to 50% of renal allografts recovered from donors after declaration of death.

Mild hypothermia in organ donors after declaration of death according to neurologic criteria reduces the rate of delayed graft function among recipients (Neimann CU et al).

Pharmacologic agents have not proved helpful in reducing the incidence or severity of delayed graft function.

Cytomegalovirus disease, cataracts, osteonecrosis, and hypertension affect a significant proportion of the population of transplant patients.

Patients with pretransplant cardiac or peripheral vascular disease and those who smoke before transplant have worse graft survival.

Recipients having more than 1 year of pretransplant dialysis have worse long-term graft survival rates.

T cells one principal regions of acute rejection that travel to and recognize the allograft.

For transplant candidates with living donors, the transplant should be done as soon as possible.

Transplantations from parents or siblings have survival outcomes similar to those from an HLA-mismatched donor.

Survival of a kidney from a living donor with no DR match is 75% at 5 years which is the same for a 1 or 2 DR mismatch between the donor and the recipient of the kidney.

Virtually all transplants from unrelated living donors in kidney transplantation are HLA mismatched.

In children the overall survival rate at 36 months is 96.6% among living donorr transplant patients and 94.8% among those receiving cadaveric kidneys.

The median survival of transplanted kidney grafts  is 11.7 years for organs from deceased donors and 19 years for organs from living donors.

Most children who receive a kidney transplant will receive more than one in their lifetime.

The 1 and 5-year survival rates for live donor allografts are 92% and 76% respectively, compared with 81% and 59% for cadaveric allografts.

Adolescents have graft survival at one year that is better than younger patients, but have a greater graft lost within a decade of transplant.

Graft losses by adolescents are partly due to physiologic and/or immunologic reasons with age, but psychological and sociological factors, can affect adherence to medication.

Adolescents between 14 and 16 years of age have worse longitudinal outcomes during a ten-year period than other age cohorts.

Half of patients who receive a cadaveric transplant will reject their kidney in just over one decade.

Patients with a resistance index of 80 or higher have a median allograft survival time of 2.5 years, compared to 23.3 years among patients with a resistance index of less than 80.

Renal arterial resistance index of 80 or higher predicts a decrease of 50% or more in creatinine clearance, allografts failure, or death.

Improved life expectancy for patients who have undergone renal transplantation as opposed to patients who have remained on dialysis.

After 2 years of functioning, a living donor renal transplant is less costly than maintaining the patient on hemodialysis.

The quality of life of recipients of successful renal transplants is superior to that of patients on dialysis.

African-Americans have lower rates for ref2242al for renal transplantation.

The rate of acute is at the lowest level ever, but the long-tem risk of graft loss has not improved.

Subclinical rejection, in the absence of an increase in serum creatinine, may be apparent only on kidney biopsy but can damage the transplanted kidney.

Kidney biopsy is typically done at 0, 3 and 12 months post-transplant according to a transplant unit protocol.

Chronic allograft dysfunction may develop after transplantation even when renal function is good in the early years after transplantation.

Infections, malignancies and cardiovascular diseases cause 11.7%, 10.1 and 30% of deaths, respectively, in kidney transplants beyond the first year after transplantation.

Detecting rejection difficult to assess since serum creatinine may rise from allograft rejection or immunosuppressive drug toxicity and ultrasonography and renal biopsy are frequently performed to aid in evaluation.

Between 1998 and 2007 78% of renal transplant patients received antibody induction medicine.

Antibody induction therapy helps to achieve early glucocorticoid withdrawal.

Antibody induction therapy includes rabbit anti-thymocyte globulin which is a lymphocyte depleting polyclonal antibody, and basiliximab, a non-lymphocyte depleting monoclonal antibody targeting the interleukin-2-receptor.

Alemtuzumab antibody induction decreases acute rejetion compared to conventional therapy (Hanaway MJ et al).

Kidney biopsies lack sensitivity to discriminate from drug induced nephrotoxicity and early transplant rejection.

After successful transplant most common cause of late mortality is cardiovascular disease, responsible for 40-55% of all deaths.

Corrects hypercoaguable state of end stage renal disease on hemodialysis.

Increased risk of acquired renal cystic disease and renal cell cancer compared to general population.

Incidence of malignancies among recipients of renal transplants ranges from 6-8.3%.

Skin cancers and lymphomas common in the U.S. after renal transplantation, while in Japan gastric and other gastrointestinal cancers are more frequent.

The development of malignancy following transplant is associated with the age of the recipient, the number of years after transplantation, the duration of hemodialysis, and the type of immunosuppressive treatment used in the management of the recipient.

Kidney transplant recipients with donor cancer transmission: The most common transmitted cancer types are renal cancers, followed by melanoma, lymphoma (n?and lung cancer.

Patients with melanoma and lung cancers that are transmitted have the worst prognosis, with less than 50% of recipients surviving after 24 months from transplantation.

Recipients with transmitted renal cancers had the best outcomes, with over 70% of recipients surviving for at least 24 months after transplantation.

Recipients have an increased risk of infection due to immunosuppressive therapy and can potentially lead to the development of lymphomas secondary to Epstein-Barr virus, or hepatoma secondary to chronic hepatitis C.

Traditionally transplants are placed in the iliac fossa with vascular access to the common or external iliac artery, and with easy access to the urinary bladder.

An anastomosis is created between the transplant renal artery and vein to the iliac vessels of the recipient and between the donor’s ureter and the recipient’s bladder.

Donor kidneys are placed in the pelvis outside the peritoneum, and the diseased native kidneys are usually left in place.

ACE inhibitors decrease erythropoietin production, and are used after renal transplant to manage post-transplant erythrocytosis, a condition characterised which often develops 8-24 months after successful transplantation.

Premature transplant failure is the fifth leading cause for the initiation of dialysis in the US.

25% of patients whose transplants fail die within 2 years after returning to dialysis.

The best option for a patient who’s transplant has failed is a second transplant.

Candidates for repeat transplantation account for 20% of patients on the waiting list, but received only 12% of the deceased donor kidneys transplanted in the US.

Among patients on dialysis at for-profit facilities compared with nonprofit facilities, there is a lower likelihood of accessing kidney transplant (Gander JC).

Prevention of acute rejection is the key to achieving long-term graft survival.

Adequate tacrolimus exposure during the first year after transplantation and after the first year at lower doses, with low-dose glucocorticoids and an antimetabolite are essential for the prevention of early acute rejection and the development of de novo donor specific antibodies.

Patients with lower grades of T-cell mediated rejection are treated with glucocorticoids,  whereas those were higher grades received anti-thymocyte globulin.

Vaccinations must be administered before transplantation and only inactivated vaccine should be given after transplantation.

CMV infection is the most common opportunistic infection after kidney transplantation and CMV seronegative patients are at increased risk for such an infection if they receive a kidney from a seropositive donor.

BK virus is common in iimmunosuppressed kidney transplant recipients.

BK viruria progresses to viremia and can lead to nephropathy and transplant failure.

BK virus nephropathy is an interstitisl nephritis which is difficult to distinguish from acute rejection unless characteristic inclusions are recognized.

BK virus infection requires reduction of immunosuppressive therapy.

There is no effective antiviral agent for BK virus and patients should be screened for viremia, with early reduction of immunosuppressive therapy.

Post transplantation lymphoproliferative disease is a frequent extranodal B cell disorder associated with Epstein-Barr virus infection.

Post transplantation lymphoproliferative disorder suggests over immunosuppression, and it can be treated with anti CD20 agents and cytotoxic chemotherapy,  when necessary,  combined with minimization of immunosuppression.

The relative risk of delayed graft function is reported to be 38% lower with the use of therapeutic hypothermia than the use of normothermia in brain dead organ donors.

Machine perfusion of kidneys from donors is increasingly being adopted in the United States.

Among the brain, dead organ donors, therapeutic hypothermia was inferior to machine perfusion of the kidneys in reducing delayed graphed function after transplantation. (Malinski D).

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