Kidney Disease Clinic Signs and symptoms managment

Kidney transplant

One of the best option of kidney failure management is Kidney transplant, it offer patients a new life, less mortality and morbidity, and it less cost among the other options.
In this few pages we If GOD Well will explore this option and will try to cover common ask questions about it.
The most important issue for kidney transplant is the patient wellness to have kidney transplant and he should know his responsibility and show commitment to obey and follow medical advices to survive transplanted kidney for long time.

When renal patient could have kidney transplant?

Dialysis patients: most kidney transplanted patients have kidney transplant after starting dialysis until available kidney donor

Pre dialysis: patient who have chronic kidney disease progress to end stage can plan for kidney transplant before they starting dialysis.
For diabetic patients can plan for kidney transplant when GFR (glomerular filtration rate) reach 20 ml per minute, while for undiabetic 15 ml per minute.
Pre-emptive transplant can improve post-transplant patient and graft survival.

Is me suitable for kidney transplant?

All renal patients less than 75 years old are suitable for kidney transplant if comorbid illness can be treated before the surgery, unfortunately there are some medical conditions cannot be cured such as:

Disseminated malignancy

Extensive vascular disease

High risk for perioperative mortality

Persistent coagulation abnormality

Some Relative contraindication include:

Renal disease with high recurrence rate

Refractory noncompliance

Urologic abnormalities

Active systemic illness

Ongoing substance abuse

Uncontrolled psychosis

What the risk factors affect kidney survival?

Major risk factors that have an impact on the recipient include age, the presence of diabetes mellitus, arteriosclerotic heart disease, chronic pulmonary disorders, and malignancy. Patient compliance

Age
The very young patient (<5 years) and the elderly recipient do have a poorer patient and graft survival than patients of ages between these two extremes. However, with the improvements in perioperative management and immuno suppressive strategies, advanced age itself is no longer a contraindication

Obesity
Obesity alone is rarely an absolute contraindication to transplantation, yet it is a well-defined risk factor.
Lower graft survival rates as well as higher postoperative mortalities and complications have been demonstrated in patients with a body mass index (BMI) greater than 30 kg/m2.
The large body size is also a risk factor for progression and subsequent premature failure, due to the physiologic changes that have been linked to nephron hyperfiltration.
weight reduction is important for an obese dialysis patient before proceeding to transplantation.

Prior Kidney Transplantation
Renal allograft failure is now one of the most common causes of ESRD, accounting for about 30% of patients awaiting renal transplantation.
Graft survival of a second and/or third kidney transplant has been reported to be inferior to that of the first.
Evaluation of a potential recipient for a second or third allograft requires careful attention to the reason for the graft failure.

Factors to be assessed include

noncompliance with immunosuppressive medications

loss of the graft in association with recurrent renal disease

high alloreactivity with high panel-reactive antibody (PRA) titers (PRA).
These patients may also manifest complications of prior immunosuppressive therapy, and as such should be screened for complications associated with these medications (e.g. infection and malignancy).

Types of kidney transplants

There are two general types of kidney transplants
one from a living donor and another from a deceased donor.
A living donor transplant is preferred to the deceased donor because these tend to be better quality kidneys in that the waitlist times tend to be low and graft survival is longer than deceased donor kidneys.

The half-life of living kidneys is around 12–14 years while that of the deceased donor is around 9 years.
The longer people wait for transplantation while on dialysis, the more unfavorable their outcomes are after transplant.
Ideally, patients would be transplanted before initiating dialysis, referred to as pre-emptive transplant, or as soon as possible after initiating dialysis.
Patients can be listed for transplant when their glomerulus filtration rate is below 20 mL/min/m2.
Statistics show that kidney transplants from live donors function longer and the survival rate for live donor kidneys is greater than 95 % for the first year.
The average life of a kidney donated from a perfectly matched (tissue typing identical) sibling is 25 to 30 years
the average life of a kidney donated from a half matched or unrelated donor is 16 years.

Deceased donor:
A deceased donor kidney comes from a person who has chosen to be an organ donor and has been declared deceased.
Like the living donor, the deceased donor must have blood testing performed to show compatibility with the proposed recipient.
The kidney transplant survival rate for the first year with a deceased donor kidney is 85 to 90 %.
The average functional time period of a deceased donor kidney transplant is between 8-20 years.

What the suitable donor for me?

Basically the donor should have blood group compatible with yours.
If blood types are not compatible, the donor still may be able to donate directly to you using treatments that lower your blood antibody levels.
In addition, the donor may consider donating through a paired exchange program which would allow you to get a kidney from another donor who is not a match for their intended recipient.

suitable donor
Recipient blood group	donor blood group
A	A and O
B	B and O
AB	A, B, AB and O
O	O

Kidney transplant and gender

The most successful transplant based on donor-recipient gender was observed in male donor to male recipient, and then male donor to female recipient.

Is There an Age Cutoff for Kidney Donors?

There is no limit for donor age, theoretically it can be from 6 to 80 years.
For the pediatric they cannot legally give their “informed consent” proving that they agree to the procedure, and there is some genetic kidney diseases cannot be detected at this age.
For elderly more than 70 may have ageing kidney
The age may not be a barrier to organ donation

Is There an Age Cutoff for Kidney Recipient?

There is no age limit for kidney transplant
https://www.youtube.com/watch?v=n8skoBVca38

Why cannot get kidney from any donor?

when you transplant kidney, your body will consider it as foreign body like bacteria and viruses , and activate the immune system attempts to destroy them to protect the body from harm, by producing cells and/or antibodies that invade and damage the kidney.
This called rejection, which result in complex process ending by damaged transplanted kidney.

How to minimize body defense against transplanted kidney?

the best way is to select donor with immune compatibile with your body.

How to select compatibile donor ?

The main part of immune system is human leukocyte antigen (HLA) system (the major histocompatibility complex [MHC] in humans), it controlled by genes located on chromosome 6.
It encodes cell surface molecules specialized to present antigenic peptides to the T-cell receptor (TCR) on T cells.
The donor with shared HLA matching will be the better.

Why HLA matching important ?

HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression.
Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy.
HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant.

How I know whether the donor is HLA match ?

you should HLA typing in medical lab for you and for the donor.
Input here the results for initial assessment

I had HLA matching test, what then ?

After decting HLA mathcing, one should screen the presence of antibodies.
Complement Dependent Lymphocytotoxicity (CDC):

IgG antibodies directed against HLA class I (on both B and T cells) are the most important

PRA stands for Panel Reactive Antibodies. In order to determine whether or not a patient already has any specific HLA antibodies

When PRA positive (there is HLA antibodies), it called the patient is sensitized, and need a procedure called desensitization

what happen if I have antibodies ?

It is not easy to become sensitized to human HLA antigens. Most people waiting for a transplant (around 80%) are not sensitized. Patients can become sensitized to HLA antigens because of:

Pregnancies. About 30-50% of women with three or more pregnancies will develop HLA antibodies. In some women the antibodies could be present for just a short time (weeks to months), while in others they may persist for many years.

Blood transfusions. About 50% of patients who receive multiple transfusions will develop antibodies. Today, most patients who require blood transfusions receive filtered blood, which decreases the chances for a patient to become sensitized.

Previous transplant. About 90% of patients develop HLA antibodies within two weeks of a failed graft. However, by the time the patient is relisted (some will have "lost" their antibodies.

Viral/bacterial infections. There are some reports that patients with virus infections develop HLA antibodies, although this is relatively rare.

what is the definition of sensitization ?

The definition of sensitization is variable. One definition defines it as moderately sensitized when PRA is >20% and highly sensitized when the PRA >80%. This is however variable between centres.

what is Desensitization Protocols of Kidney Transplant Recipients ?

Removal of anti-HLA antibodies
- Plasmapheresis
- Immunoadsorption
- IdeS
Depletion of antibody-producing cells
- Naïve and memory B cells: rituximab (anti-CD20)
- Plasma cells: bortezomib (proteosomal inhibitor)
Inhibition of antibody and complement-system cascade
- IVIg
- Complement inhibitors
  - Eculizumab (C5a inhibitor)
  - C1 inhibitor
Inhibition of cytokines and inflammation
- IVIg
- Tocilizumab (anti–IL-6 receptor blocker)

Abbreviations: IdeS, immunoglobulin G-degrading enzyme of Streptococcus pyogenes; IL-6, interleukin 6; IVIg, intravenous immune globulin.

what is PLASMAPHERESIS AND IMMUNOADSORPTION ?

Both these techniques are aimed at removing alloantibodies.

PP removes all plasma proteins including Ig.

IA includes a sepharose-bound staphylococcal protein A column with a high affinity for binding IgG and developed to remove IgG antibodies.

The advantages of IA over PP include specificity, a greater amount of antibody removal, and the elimination of the need to replace large volumes of plasma.

One 3- to 4-hour treatment course with IA results in a 15% to 20% reduction and three to six courses of treatment result in 90% reduction in plasma IgG levels.

However, anti- HLA antibody titers rebound and return to baseline levels within a few weeks after the completion of PP or IA.

Most of the IA columns manufactured in USA and Japan are not approved by the FDA

INHIBITION OF ANTIBODY PRODUCTION & COMPLEMENT INHIBITORS ?

Based on inhibiting antibody production by B-cells and plasma cells.

Rituximab (Anti-CD 20):
- off label use in desensitization protocol/treatment of AMR as a single dose of 375mg/m².
- Plasma cells and pro-B cells do not have surface CD-20 decreasing the efficacy.
- B-cell recovery takes 6-12 months.
Bortezomib (Proteasomal Inhibitor):
- Induces apoptosis of plasma cells.
- Given in dosage of 1.3 mg/m² and repeated on days 4, 8, and 11 intravenously over 3 to 5 seconds.
- It is a monoclonal antibody against C5.
- Binds to C5 protein with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing generation of the terminal complement complex C5b-9.

Person	Class A	Class B	Class DR
Reciepent
Doner