4) Chronic Kidney disease drug therapy

Question 1

What is the UF coefficient

Answer 1

volume of ultrafiltrate per hour, divided by the pressure gradient across the membrane

ie the membrane’s effectiveness to filter the fluid.

Question 2

Clearance

Answer 2

How many ml of blood is totally cleared of a given molecule in 1 minute.

Question 3

Sieving coefficient

Answer 3

Membrane permeability of the membrane to a specific molecule

Question 4

Surface

Answer 4

total surface of the capillary membrane in the unit

Question 5

Blood volume

Answer 5

the amount of dialysed whole blood in mL

Question 6

TMP

Answer 6

transmembrane pressure

Question 7

TMP

Answer 7

transmembrane pressure

Question 8

What are dialysis membranes made out of?

Answer 8

Cellulose 20 micron pore size

Cellulose acetate

Polyacrylonitrile, PAN

Polysulfone - 40 micron pore size

Polpropylene

Question 9

What are the uremic toxins

Answer 9

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

Question 10

Anticoagulants used for hemodialysis, what are they

how are they administered

Answer 10

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

Question 11

When are the anti-coagulants contraindicated during AKI or CKD?

Answer 11

Uremic pericarditis

Hypertensive crisis

Any acute cerebrovascular events/strokes

Gastroenteritis with bleeding danger

Proliferative diabetic retinopathy

Question 12

Who should be referred to a nephrologist?

Answer 12

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.

Question 13

What needs to be matched for organ transplant allocation

Answer 13

Blood group compatibility, ABO, Rh does not matter

HLA matching for
HLA-A HLA-B and HLA-DR
Human leukocyte antigen

Age,
Gender,
size

Question 14

blood group compatibilities

How does this differ for allocation?

Answer 14

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

Question 15

Allocation procedure

Answer 15

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

Question 16

Determining actual eligibility

Answer 16

Vital parameters, is the patient stable

Renal exam, do they meet requirements for need

Surgical consult, exam. Can they withstand surgery.

Anesthesiological consult.

Question 17

Preoperative care for renal transplant

Answer 17

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.

Question 18

Kidney transplant placement
vessel attachments
ureter attachment

Answer 18

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.

Question 19

Types of donors

Answer 19

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.

Question 20

Early post-op care for transplant

Answer 20

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.

Question 21

Complications of renal transplantation

Answer 21

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

Question 22

Common infections after transplants

Answer 22

HSV
CMV
Hepatitis, HBV, HVC
EBV
VZV
Fungal infections
Nocardia
Toxoplasma
Cryptococcus

Question 23

Common tumors after transplants

Answer 23

Skin cancers are especially common.
sq. cell carcinoma,
melanoma,
baslioma

Other cancers incidence also all increase.

Question 24

What is PRA and sensitization

Answer 24

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.

Question 25

Graft survival estimates in years based on HLA mismatch

Answer 25

no mismatch: ~40% survival at 20 years, 17 year half life. 1 MM: 37%, 15 year half life 2 MM: 36% 6 MM: 29%

Question 26

Graft survival from siblings

Answer 26

60% survival in HLA matched siblings, 28 year half life

Question 27

Markers of graft survival

Answer 27

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,

Question 28

Immunosuppressive drugs classes used after transplants, Incidence of acute graft rejection

Answer 28

Acute rejection is ~10-15% Steroids: Prednisolone Antimetabolites: mycophenolate mofetil, azathioprine mTOR-inhibitors: Sirolimus Calcineurin inhibitors: cyclosporin

Question 29

Advantages of living donor over cadaveric donors

Answer 29

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%

Question 30

How does the GFR change for the living donor?

Answer 30

Immediate drop to 50%, then compensatory hypertrophy of the remaining kidney and increase back to about 70%

Question 31

What is the 'safe' GFR needed for a living donor to be eligible

Answer 31

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.

Question 32

Absolute contraindications for Renal transplantation

Answer 32

``` Active infections Active Glomerulonephritis HIV HBV Cancer with likely metastases Severe heart disease or other severe comorbidity, low survival. ```

Question 33

Relative contraindications for transplant

Answer 33

Age over 70

Question 34

1st line agents for treating blood pressure in CKD | Stages 1-3

Answer 34

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.

Question 35

Treated blood pressure in CKD stage 4-5

Answer 35

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.

Question 36

Duration of dialysis and rate of blood flow through the machine Total extracorporeal blood during dialysis

Answer 36

4 hours for each treatment, Blood is dialyzed at a rate of 200–400 mL/min 80-250mL extracorporeal

Question 37

Treatment of renal osteodystrophy

Answer 37

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.

Question 38

Who should be referred to a nephrologist

Answer 38

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

Question 39

What must be matched/checked for allocation of a kidney transplant

Answer 39

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.

Question 40

blood type matching

Answer 40

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 ```