4) Chronic Kidney disease drug therapy Flashcards
What is the UF coefficient
volume of ultrafiltrate per hour, divided by the pressure gradient across the membrane
ie the membrane’s effectiveness to filter the fluid.
Clearance
How many ml of blood is totally cleared of a given molecule in 1 minute.
Sieving coefficient
Membrane permeability of the membrane to a specific molecule
Surface
total surface of the capillary membrane in the unit
Blood volume
the amount of dialysed whole blood in mL
TMP
transmembrane pressure
TMP
transmembrane pressure
What are dialysis membranes made out of?
Cellulose 20 micron pore size
Cellulose acetate
Polyacrylonitrile, PAN
Polysulfone - 40 micron pore size
Polpropylene
What are the uremic toxins
Small MW toxins: purines, oxalate, myoinositol
Middle weight uremic toxins: Beta-2 Microglobulin Peptides Advanced-glycation-endproduct proteins AGE-proteins Variable peptides
Small MW solutes with ‘medium behavior’:
Homocysteine
Phenols
Chloramines
Anticoagulants used for hemodialysis, what are they
how are they administered
They are administered by the dialysis machine into the extracorporeal blood, prior to entering the dialysis capillary, preventing thrombosis from occuring in the machine.
Heparin - AT3 activation, thrombin inhibition
Hirudin; direct thrombin inactivator.
Citrate - calcium chelator
Prostacyclin - platelet inhibitor
Warfarin - VKOR inhibition
When are the anti-coagulants contraindicated during AKI or CKD?
Uremic pericarditis
Hypertensive crisis
Any acute cerebrovascular events/strokes
Gastroenteritis with bleeding danger
Proliferative diabetic retinopathy
Who should be referred to a nephrologist?
Nephrotic syndrome
Proteinuria or hematuria -everyone urgently
Urine Protein:Cre ratio: above 350mg/mM - everyone
UPCR above 100mg/mM - everyone except diabetics
UPCR above 45 mg/mM - if concurrent microhematuria or suspected autoimmune disorder.
Macrohematuria with proteinuria -urgently everyone
macrohematuria without proteinuria - refer if UTIs, urologic causes have been excluded.
What needs to be matched for organ transplant allocation
Blood group compatibility, ABO, Rh does not matter
HLA matching for
HLA-A HLA-B and HLA-DR
Human leukocyte antigen
Age,
Gender,
size
blood group compatibilities
How does this differ for allocation?
Donor: A
Recipient A or AB
Donor: B
Recipient: B or AB
Donor: AB
Recipient: AB
Donor: O
Recipient O or A or B
For allocation:
Group A donors can only go to A recipients, and Group A recipients can only receive from A donors.
Group O donors cannot go to A recipients
Allocation procedure
Donor typing from blood
Pre-cross match from sera of recipients
Selection based on waiting list priority:
Age, Urgency, highly immunized state
Is patient eligibility good? Contact patient and discuss
Recipient comes in and is examined.
Final crossmatch from the donor spleen and final decision
Determining actual eligibility
Vital parameters, is the patient stable
Renal exam, do they meet requirements for need
Surgical consult, exam. Can they withstand surgery.
Anesthesiological consult.
Preoperative care for renal transplant
Preoperative dialysis if needed.
Begin immunosuppression therapy
Antihypertensive therapy
PPI prophylaxis for ulcers
Antibiotic prophylaxis for infections
For patients with high sensitization/ Panel Reactive Antibodies, consider induction immunosuppression therapy, using monoclonal or polyclonal antibodies against T-cell receptors CD3.
Kidney transplant placement
vessel attachments
ureter attachment
In the illiac fossa,
Connected to the common illiac artery and vein.
or external/internal illiac a. and v.
Ureter can be implanted directly onto a new site on the bladder,
or
Uretero-ureteral anastomosis.
Types of donors
Cadaveric donor:
From brainstem-dead donors with beating hearts, on ventilation and circulatory support.
From non-heart heart beating donors - require more rapid retrieval.
Living related donors - Best option, well planed procedure, best HLA matching and graft survival
Living unrelated donors - often between spouces, have to meet the ULTRA requirements.
Early post-op care for transplant
1-2 weeks post op.
General wound care and monitoring
Medications: Immunosuppressants Blood pressure Blood sugar Heparin - transitioning to NSAID PPIs
Dialysis and renal biopsy if AKI/failure begins.
Complications of renal transplantation
Renal: Rejection Delayed graft function Recurrent kidney disease New kidney disease Stones Graft failure Surgery complications
Extrarenal: HTX New onset diabetes mellitus Dyslipidemia Cardiovasular problems Hematologic complications Marrow suppression, pancytopenia Osteopenia Infections Tumors Delayed wound healing Pyschological disorders, depression
Common infections after transplants
HSV CMV Hepatitis, HBV, HVC EBV VZV Fungal infections Nocardia Toxoplasma Cryptococcus
Common tumors after transplants
Skin cancers are especially common.
sq. cell carcinoma,
melanoma,
baslioma
Other cancers incidence also all increase.
What is PRA and sensitization
Panel Reactive Antibody (PRA) is an immunological laboratory test routinely performed on the blood of people awaiting organ transplantation. The PRA score is expressed as a percentage between 0% and 99%. It represents the proportion of the population to which the person being tested will react via pre-existing antibodies.
Higher sensitization, higher likelyhood for graft rejection.
Graft survival estimates in years based on HLA mismatch
no mismatch: ~40% survival at 20 years, 17 year half life.
1 MM: 37%, 15 year half life
2 MM: 36%
6 MM: 29%
Graft survival from siblings
60% survival in HLA matched siblings, 28 year half life
Markers of graft survival
Renal function
Proteinuria
Emergence of donor-specific antibodies in patients serum - indicate onset of antibody injury to graft.
ex: anti-HLA abs, anti-non-HLA
Graft biopsy and histology for early or late rejection,
Immunosuppressive drugs classes used after transplants,
Incidence of acute graft rejection
Acute rejection is ~10-15%
Steroids: Prednisolone
Antimetabolites: mycophenolate mofetil, azathioprine
mTOR-inhibitors: Sirolimus
Calcineurin inhibitors: cyclosporin
Advantages of living donor over cadaveric donors
Kidney will immeidately function, and does not require a post-operative dialysis phase
Half life is 20 years instead of 13 years
1 year graft survival 95% instead of 90%
How does the GFR change for the living donor?
Immediate drop to 50%,
then compensatory hypertrophy of the remaining kidney and increase back to about 70%
What is the ‘safe’ GFR needed for a living donor to be eligible
based on the ERBP european renal best practice guideline.
Safe GFR ensures that by the best estimate, the patients GFR at age 80 will be at least 37.5
Before age 45, the donors GFR should be at least 80.
Absolute contraindications for Renal transplantation
Active infections Active Glomerulonephritis HIV HBV Cancer with likely metastases Severe heart disease or other severe comorbidity, low survival.
Relative contraindications for transplant
Age over 70
1st line agents for treating blood pressure in CKD
Stages 1-3
ACEIs/ARBs and Loop diuretics (FUrosemide)
1st line: ACEIs or ARBs,
i. especially for diabetics with elevated ACR (>3mg/mM), microalbuinuria ii. Hypertension and ACR >30, proteinuria/nephrosis iii. Any patient with ACR >70, severe nephrosis iv. Dual therapy is contraindicated, just one.
Treated blood pressure in CKD stage 4-5
ACEIs/ARBs, Furosemide, and add Thiazide or Spironolactone
Spironolactone contrad if eGFR <30
-spironolactone inhibits aldosterone receptors, and can cause hyperkalemia if GFR is too low.
Duration of dialysis and rate of blood flow through the machine
Total extracorporeal blood during dialysis
4 hours for each treatment,
Blood is dialyzed at a rate of 200–400 mL/min
80-250mL extracorporeal
Treatment of renal osteodystrophy
Phosphate control:
1) Limit phosphate intake
2) Treat with phsophate binders:
- CaCo3 and Ca-Acetate, CKD 3-5
- Sevelamer, Lanthanum, CKD 5d
Vitamin D supplementation:
Correct nay measured deficiency, give native vitamin D or active vitamin D.
Treat secondary hyperPTHism: administer calcimimetic drug to inhibit PTH release.
Who should be referred to a nephrologist
GFR less than 15 unless it is pre mortem
GFR 15-29 always, urgenly if stable
GFR 30-60 and under aged 70 years
- or eGFR falling more than 4ml/year - Hb < 110g/L or ion imbalance
GFR 60-90 if there is evidence of nephritis/nephrosis
What must be matched/checked for allocation of a kidney transplant
Must be matched/have compatible ABO blood groups. Rh does not matter
Must have a negative crossmatch, mixing the patients serum with the blood of the donor and/or with cells from the donor. If the patients blood does not react to the donors then it is a negative, and the donoation can proceed.
HLA matching for the 6 HLA antigens is beneficial and higher matching will prolong the life of the donated kidney, but is NOT absolutely required for the transplant to occur, it is just strongly beneficial.
blood type matching
Blood Type Compatibility Chart
Blood Type: Can Donate To: O A,B, AB, O A A or AB (O)* B B or AB AB AB
Blood Type: Can Receive From: O O (A)* A A or O B B or O AB A or B or AB or O
