Seminar on Renal Transplantation

8/2/2019 Seminar on Renal Transplantation

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Seminaron

kidney transplantation

Presented by,Mrs Bibi BabyII year MSc(N)

Medical surgical nursing.


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HISTORICAL REVIEW OF KIDNEY TRANSPLANTATION


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DEFINITION OF KIDNEY TRANSPLANTATION

Kidney transplantation or renaltransplantation is the organ transplant of akidney into a patient withend-stage renal disease .

A kidney transplant is a surgical procedure inwhich a kidney is removed from one person(donor) and placed into the body of a personsuffering from renal failure (recipient), in

whom the transplanted kidney can perform allthe functions which the patient's own kidneysare not able to perform.
http://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Chronic_kidney_diseasehttp://en.wikipedia.org/wiki/Chronic_kidney_diseasehttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Organ_transplant


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CONTRAINDICATIONS OF KIDNEY TRANSPLANTATION

Certain infections, such as TB or boneinfections.

Recent history of cancer.

Infections such as hepatitis .

Smoking, alcohol or drug abuse, or

other risky lifestyle habits.Serious cardiac or

peripheral vascular disease .

Hepatic insufficiency.
http://www.nlm.nih.gov/medlineplus/ency/article/000077.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/001154.htmhttp://emedicine.medscape.com/article/761556-overviewhttp://emedicine.medscape.com/article/761556-overviewhttp://www.nlm.nih.gov/medlineplus/ency/article/001154.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/000077.htm


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Severe obesity (BMI of greaterthen 35).History of noncompliance to

medical therapy.Active infections.HIV Positive.Active substance abuse.Active psychiatric disorder which

remains untreated or is


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SOURCES OF KIDNEY


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Immunology of graftrejections


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Types of grafts:

1. Xenografts, which are grafts between

members of different species, have the mostdisparity and elicit the maximal immuneresponse, undergoing rapid rejection.

2. Autografts, which are grafts from one part of the body to another , are not foreign tissueand, therefore, do not elicit rejection.

3. Isografts, which are grafts betweengenetically identical individuals (eg,monozygotic twins), also undergo norejection.

4. Allografts are grafts between members of

the same species that differ genetically. Thisis the most common form of trans lantation.


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Genetic background

The antigens responsible for rejection of genetically disparate tissues are calledhistocompatibility antigens; they are productsof histocompatibility genes.

In humans, the MHC is called the humanleukocyte antigen (HLA) system and is locatedon the short arm of chromosome 6, near thecomplement genes.

The MHC genes are codominantly expressed,which means that each individual expressesthese genes from both the alleles on the cellsurface. Furthermore, they are inherited as

haplotypes or 2 half sets (one from each


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The MHC molecules are divided into 2 classes.

The class I molecules are normally expressedon all nucleated cells,

class II molecules are expressed only on theprofessional antigen-presenting cells (APCs),

such as dendritic cells, activatedmacrophages, and B cells.

The physiological function of the MHCmolecules is to present antigenic peptides to Tcells, since the T lymphocytes only recognizeantigen when presented in a complex with anMHC molecule.

q The class I molecules are responsible forpresenting antigenic peptides from within the


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Sensitization stage

In this stage, the CD4 and CD8 T cells, viatheir T-cell receptors, recognize the alloantigensexpressed on the cells of the foreign graft. Twosignals are needed for recognition of anantigen;

the first is provided by the interaction of the T cell receptor with the antigen presented by

MHC molecules,

the second by a costimulatory receptor/ligandinteraction on the T cell/APC surface. Of thenumerous costimulatory pathways, theinteraction of CD28 on the T cell surface with

its APC surface ligands, known as CD80 orCD86. In addition, c totoxic T l m hoc te


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Direct pathway

In the direct pathway, host T cells recognizeintact allo-MHC molecules on the surface of

the donor or stimulator cell. Mechanistically,host T cells see allo-MHC molecule + allo-peptide as being equivalent in shape to self-MHC + foreign peptide and, hence, recognizethe donor tissue as foreign. This pathway ispresumably the dominant pathway involved inthe early alloimmune response.

The transplanted organ carries a variable

number of passenger APCs in the form of interstitial dendritic cells. Such APCs have a


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Indirect pathway

In the indirect pathway, T cells recognizeprocessed alloantigen presented as peptidesby self-APCs. Secondary responses such asthose that occur in chronic or late acuterejection are associated with T cellproliferative responses to a more variablerepertoire, including peptides that werepreviously immunologically silent. Such achange in the pattern of T cell responses hasbeen termed epitope switching or spreading.A link between self-MHC + allopeptide-primed

T cells and the development of acute vasculartype rejection has been demonstrated to bemediated in part by accelerated alloantibody


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Molecular mechanisms of T cellactivation

During T cell activation, membrane-bound inositol phospholipid is hydrolyzed intodiacylglycerol (DAG) and IP3. This increases thecytoplasmic calcium. The elevation in calciumpromotes the formation of calcium-calmodulincomplexes that activate a number of kinases aswell as protein phosphatase IIB or calcineurin.Calcineurin dephosphorylates cytoplasmicnuclear factor of activated T cells (NFAT),permitting its translocation to the nucleus,where it binds to the IL-2 promoter sequenceand then stimulates transcription of IL-2 mRNA.Numerous other intracellular events, including


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Effector stage

Alloantigen-dependent and independentfactors contribute to the effector mechanisms.Initially, nonimmunologic "injury responses"(ischemia) induce a nonspecific inflammatoryresponse. Because of this, antigenpresentation to T cells is increased as theexpression of adhesion molecules, class IIMHC, chemokines, and cytokines isupregulated. It also promotes the shedding of intact, soluble MHC molecules that mayactivate the indirect allorecognition pathway.After activation, CD4-positive T cells initiatemacrophage-mediated delayed typehypersensitivity (DTH) responses and provide


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Apoptosis

The final common pathway for the cytolyticprocesses is triggering of apoptosis in thetarget cell. After activation of the CTLs, theyform cytotoxic granules that contain perforin

and granzymes. At the time of target cellidentification and engagement, these granulesfuse with the effector cell membrane andextrude the content into the immunological

synapse.


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Role of natural killer cells

The natural killer (NK) cells are important in

transplantation because of their ability todistinguish allogenic cells from self and theirpotent cytolytic effector mechanisms.[4]

These cells can mount a maximal effectorresponse without any prior immunesensitization. Unlike T and B cells, NK cells areactivated by the absence of MHC moleculeson the surface of target cells (missing selfhypothesis). The recognition is mediated byvarious NK inhibitory receptors triggered by


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RENAL PRESERVATIONS

Preservation solutionsVarious flush solutions are used for

organ preservation. Each

substantially differs in theircomposition, but the purposes of each are similar: to prevent cellular

edema, to delay cell destruction, andto maximize organ function afterperfusion is reestablished.


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Euro-Collins solution

Euro-Collins solution was developed as amodification of the original Collins solutionand contained high concentrations of potassium (110 mM), phosphate (60 mM), andglucose (180 mM). Organ preservationimproved with the use of Euro-Collins solution.When it was used for kidney preservation,delayed renal function after implantation wassignificantly reduced.

Bretschneider histidine tryptophanketoglutarate solution

Bretschneider histidine tryptophan

ketoglutarate (HTK) solution was found to be


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University of Wisconsinsolution The solution


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Hydroxyethyl starch (HES) 50 g/L

Bactrim 0.5 ml/L

The lactobionate is the major effectivecomponent of the solution. Its insoluble naturemaintains the colloid oncotic pressure of the

solution, delaying or preventing equilibrationof the solution across the cell membrane, andthus delaying the development of cellularedema.

The lowered concentration of potassiumimproves the flushing efficiency of thesolution by removing the vasoconstrictiveeffect of the high potassium solution.

Glutathione is unstable in solution and


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Hypothermic preservation

Two techniques of hypothermic preservation areused: simple cold storage and continuoushypothermic perfusion.

With simple cold storage, the organ is flushed

with cold preservative solution and placed in asterile bag immersed in the solution. Thesterile bag is placed inside another bag thatcontains crushed ice. Advantages of simplecold storage include universal availability andease of transport.

With continuous hypothermic perfusion, whichBelzer developed in 1967, a machine is used

to continuously pump perfusion fluid through


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Ethical issues in transplantation

1. It is the right of individuals todonate as well as to receive an organ.

2. Commercially motivated renaltransplantation is unacceptable, hasbeen widely prohibited by law, and

the International Society of Transplantation strongly opposes itspractice.

3. Given the increasing success of


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5. A patient should be treated as an end

and not as a means. Respect for dignity,integrity and authenticity of the person is abasic human right .

6. Acceptance of living unrelated donorsshould be done only after the local ethicalcommittee has given permission or, asrequired by the country, permission by theCourts .

7. In the last instance, what is and what isnot ethical should be determined by thebalance between clinical utilitarian

demand (saving lives in a cost-effective


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Pre operative management before thekidney transplantation procedure:

Emotional and physical preparation of thepatient for surgery.

Informed consent for transplantation and

availability of potential donars. The need of immunosuppressive drugs and

measures to prevent infection must bereviewed.

Dialysis may be required before surgery forany significant abnormality such as fluidoverload and hyperkalemia.

Inform the patients about the need for dialysisor da s or weeks because the kidne there is a


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Investigations to be done before kidneytransplantation.

Tissue and blood typing to help make sure thatthe body will not reject the donated kidney

Blood Type matching

The first test establishes blood type. There arefour blood types A, B, AB and 0. Everyone fitsinto one of these inherited groups. The recipientand donor must have either the same blood typeor compatible ones. The list below showscompatible types.

If blood type is A, donor blood type must be A

or O
http://www.nlm.nih.gov/medlineplus/ency/article/003550.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003345.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003345.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003550.htm


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Tissue Typing

This involves matching of a type of white

blood cell called "lymphocytes". These cells(in fact, all body cells) have special markerscalled antigens on their surfaces. It is nowknown that a special group of these antigens,

called HLA (Human Leukocyte Antigens) areimportant in transplantation. The closer thematch of antigens between patient and donor,the better the chance of a successfultransplant.

Since these antigens are inherited fromparents, each child inherits half of theirantigens from each parent. Therefore, if a

parent is the prospective donor for the child,the will share at least one hal o the


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Procedure The renal artery of the kidney, previously

branching from the abdominal aorta in thedonor, is often connected to theexternal iliac artery in the recipient.

The renal vein of the new kidney, previouslydraining to the inferior vena cava in thedonor, is often connected to theexternal iliac vein in the recipient.
http://en.wikipedia.org/wiki/Renal_arteryhttp://en.wikipedia.org/wiki/Abdominal_aortahttp://en.wikipedia.org/wiki/External_iliac_arteryhttp://en.wikipedia.org/wiki/Renal_veinhttp://en.wikipedia.org/wiki/Inferior_vena_cavahttp://en.wikipedia.org/wiki/External_iliac_veinhttp://en.wikipedia.org/wiki/External_iliac_veinhttp://en.wikipedia.org/wiki/Inferior_vena_cavahttp://en.wikipedia.org/wiki/Renal_veinhttp://en.wikipedia.org/wiki/External_iliac_arteryhttp://en.wikipedia.org/wiki/Abdominal_aortahttp://en.wikipedia.org/wiki/Renal_artery


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Kidney-pancreas transplant

The kidney is transplanted together with thepancreas . This is done in patients withdiabetes mellitus type 1 , in whom thediabetes is due to destruction of the beta cells

of the pancreas and in whom the diabetes hascaused renal failure ( diabetic nephropathy ).
http://en.wikipedia.org/wiki/Pancreashttp://en.wikipedia.org/wiki/Diabetes_mellitus_type_1http://en.wikipedia.org/wiki/Beta_cellhttp://en.wikipedia.org/wiki/Diabetic_nephropathyhttp://en.wikipedia.org/wiki/Diabetic_nephropathyhttp://en.wikipedia.org/wiki/Beta_cellhttp://en.wikipedia.org/wiki/Diabetes_mellitus_type_1http://en.wikipedia.org/wiki/Pancreas


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Typical Postoperative Orders for theKidney Transplant Patient :

Fluid: 0.45% normal saline cc: cc replacementper hour up to 500 cc/hour. Vital signs andpulse oximetry: Every 1 hour times 12; every2 hours times 12, then every hour if stable.

Incentive spirometer : Every 2 to 4 hours.

Intake and output: Hourly first 12 hours thenevery 2 hours.

Foley irrigation PRN if clots are present.

CVP every hour times four, then every 2 hourstimes four, then every 4 hours.

Glucometer: If diabetic, check every 6 hours.


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Labs: CBC, chemistry, glucose, phosphorus,magnesium, calcium. Postoperative day 3,immunosuppressive drug levels.

Analgesia: Morphine 1-10 mg every hour forthe first 48 hours then oxycodon (Percocet[R])or propoxyphene (Darvocet[R]) 1 to 2 tabletsevery 4 to 6 hours PO.

Compression device until ambulatory.


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A calcium channel blocker such as verapamil(Calan[R]) (5 mg) also may be administereddirectly into the renal artery to reducecapillary spasm and improve renal blood flow.Caution should be exercised with usingverapamil for patients who have a history of

taking beta blocker antihypertensivemedications

Pain management in the transplant patientconsists of morphine administeredintravenously every 2 to 3 hours for the first24 to 48 hours . Pain should be assessed usingthe self-reporting pain visual analog scale andcompared with vital signs.

A re imen of immunosu ressive or anti-


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Urine output must be monitored and recordedhourly, with output replaced on an hourly

milliliter-for-milliliter basis. If the patient ishypovolemic or an attempt is being made toincrease urine output, 0.9% normal saline canhe administered intravenously as fluid bolusesof 250 to 500 ml over 1 hour.

The transplant team will provide detailedinstructions on what should be avoided post-transplant. After recovery, the patient will still

have to be vigilant about exposure to virusesand other environmental dangers.

Transplant recipients may need to adjust theirdietary habits. Certain immunosuppressive

medications cause increased appetite or


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There are three types of rejection:

a) Hyperacute Rejection - Hyperacuterejection occurs within minutes to hours afterthe release of the vascular clamps to thetransplanted kidney. In spite of aggressive

treatment with anti-rejection medications,hyperacute rejection often leads to graft loss.Even with sophisticated cross-matchingprocedures, a hyperacute rejection episodestill may occur in approximately 5% of patients .

b) Acute Rejection - Acute rejection occursdays to weeks after the transplant and is

manifested by signs and symptoms such as
http://findarticles.com/p/articles/mi_qa3867/is_4_129/ai_n32372880/?lc=int_mb_1001


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Chronic Rejection - occurs slowly over a longperiod of time and there may be no obvious

symptoms. Chronic rejection leads to late graftloss, occurs insidiously over months to years,and results in progressive loss of renal function.Chronic rejection can be due to noncompliance

with immunosuppressive medications, the ageof the transplant, and/or use of medications/herbal supplements that decreaseimmunosuppression medication levels. In

kidney recipients, chronic rejection (calledchronic allograft nephropathy) manifests asfibrosis and glomerulopathy. The followingfactors increase the risk of chronic rejection:

Previous episode of acute rejection.


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InfectionBecause the drugs used to prevent

and control rejection also weaken the bodysdefences, patients are more prone to infectionafter transplant. Risk of infection commonly inthe wound site, mouth, urinary tract and lungsis highest in the first few months after

transplant because drug dosage is highest. This is the reason for strict infection control inthe transplant ward. Whilst some infectionscan be very serious, most are controlled by

antibiotics and/or reducing doses of anti-


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Cardio vascular disease

Transplant recipients have an increasedincidence of atherosclerotic vascular disease.Cardiovascular disease is the leading cause of death after renal transplantation.Hypertension, hyperlipidemia, diabetesmellitus, smoking, rejection, infections andincreased homocysteine levels can allcontribute to cardiovascular disease.Immunosupressants can worsen hypertensionand hyperlipidemia levels. It is important thatthe patient be taught to control risk factors.


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Corticosteroid related complications

Aseptic necrosis of hips, knees and other joints can result from chronic corticosteroids

theraphy and renal osteodystrophy. Othersignificant problems related to corticosteroidsinclude peptic ulcer disease, glucoseintolerance and diabetes, cataracts,hyperlipidemia, and an increased incidence of infections and malignancies. vigilantmonitoring fro side effects of corticosteroidsand early treatment is essential.


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Advantages of transplantation overdialysis .

1. There is no dependence on the machinethrice a week for the rest of one's life.2. There are hardly any restrictions in the dietand fluid intake after a successful transplant.3. The physical sense of well-being is so muchbetter that one can go back to work in a stylesimilar to that before the illness.4. Usually the anaemia (and feeling of tiredness) seen in patients with renal failure isreversed after a successful transplant, since thekidney is functioning to maintain normal red cellproduction. For patients on dialysis, correction

of anaemia requires life-long use of


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Seminar on Renal Transplantation

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