Renal transplant and renal replacement therapy

Question 1

What is the ideal feline renal allograft recipient?

Answer 1

A cat with significant, compensated CKD that is otherwise healthy

Question 2

When should renal transplantation be performed?

Answer 2

Controversial - some centers use a minimum creatinine of 4.0 mg/dL as a cutoff

Question 3

What disease conditions rule out a cat for transplantation and should be tested for?

Answer 3

FIV, FeLV, moderate to severe heart disease, neoplasia, pyelonephritis, other significant comorbities (Toxoplasmosis, etc)

Question 4

What disease conditions should be tested for and addressed before transplant?

Answer 4

Systemic hypertension, hyperthyroidism, active infections, periodontal disease

Question 5

During transplantation, warm ischemic time of the donor kidney should be limited to how long?

Answer 5

<60 minutes

Question 6

The donor kidney can be flushed with what solution to store for up to 7 hours before transplantation?

Answer 6

Cold sucrose phosphate solution

Question 7

What drugs are used for immunosuppression post-operatively?

Answer 7

Cyclosporine and prednisolone

Question 8

Cyclosporine absorption varies among cats. How often should cyclosporine levels be monitored post-operatively?

Answer 8

Weekly until the right dose is identified, then every 3 months

Question 9

What complication has been reported acutely after renal transplantation and is associate with neurologic signs (60% of cats in one study)?

Answer 9

Severe hypertension (>170 mmHg)

Question 10

What drug can be used to mitigate post-transplant hypertension?

Answer 10

Hydralazine

Question 11

What is delayed graft function?

Answer 11

• Lack of function in an allograft with otherwise normal blood flow and no evidence of obstruction
• Creatinine >3 for 3 days after transplantation

Question 12

What causes delayed graft function?

Answer 12

Pre-, peri-, or intraoperative graft injury

Question 13

What are clinical signs of an acute graft rejection?

Answer 13

Palpable enlargement of the allograft, hyperthermia or hypothermia, malaise, loss of appetite, weight loss, worsening azotemia

Question 14

How is an acute rejection reaction treated?

Answer 14

IV immunosuppressives and fluid therapy until creatinine plateaus

Question 15

What is chronic allograft nephropathy?

Answer 15

Chronic, gradual loss of allograft function characterized by interstitial fibrosis and tubular atrophy

Question 16

What percent of feline allografts have evidence of chronic allograft nephropathy on histopathology?

Answer 16

70%

Question 17

What percent of renal transplant patients develop infections?

Answer 17

25-36%

Question 18

Following renal transplantation, what is the increased risk of cancer compared to age matched controls?

Answer 18

6 fold increase in cancer risk

Question 19

What is the 6 month survival rate for cats undergoing renal transplantation? 3 year survival rate?

Answer 19

6 month: 60-65%
3 year: 40%

Question 20

What is the median survival time of dogs after renal transplant?

Answer 20

Terrible 24 days in one study, 8 months in another study

Question 21

What percent of feline donors for renal transplant have no long term effects? What percent develop renal insufficiency? Die from urinary tract disease?

Answer 21

• 84% had no long term effects
• 5% developed CKD (2 died)
• 2% developed AKI
• 4% developed acute ureteral obstruction and died

Question 22

What are the indications for renal replacement therapy (RRT) in dogs and cats?

Answer 22

• Anuric or severe oliguric AKI
• Refractory life threatening hyperkalemia
• Refractory hypervolemia
• Severe or progressive azotemia (>5)

Question 23

How is diffusion used in hemodialysis? What molecular weight molecules can it remove? Name 2 molecules that are removed via diffusion

Answer 23

High concentrations of a molecule within the blood move are in low concentrations in the dialysate, leading to movement of molecules out of the blood

Can be used for molecules from 500- 10,000 Daltons

BUN and phosphate

Question 24

What is the equation for diffusion flux in hemodialysis?

Answer 24

Diffusion flux = -KoA x C

Ko: mass transfer coefficient (membrane permeability)
A: membrane surface area
C: concentration gradient

Question 25

What is convection and how is it used in hemofiltration? What size molecules can be removed?

Answer 25

Removal of solutes by solvent drag - solutes in the ultra filtrate are transported through a membrane by the flow of solvent. Higher pressure exists in the blood than in the ultra filtrate to push water and solutes across the membrane Can be used for middle sized molecules: 10,000 - 50,000 Daltons as well as small molecules Ex. FGF23, cytokines, endothelin, leptin

Question 26

What is ultrafiltration?

Answer 26

Movement of water across a semipermeable membrane

Question 27

What is adsorption and how is it used in hemoperfusion? What types of molecules can it remove?

Answer 27

Uses a sorbent substance (activated charcoal, etc) within a filter to remove toxins/solutes from the blood Can remove more protein or lipid bound molecules that hemodialysis or hemofiltration Can remove solutes up to 40,000 Dalton with 90-95% protein binding

Question 28

Compared the sizes and protein binding of molecules removed via hemodialysis, hemofiltration, hemoperfusion, and TPE

Answer 28

Question 29

What are 2 major determinants of dialysis disequilibrium?

Answer 29

Degree of azotemia Rate of solute removal

Question 30

What is volume of distribution and what do the values indicate?

Answer 30

Description of the theoretic distribution of a solute throughout the body Water is 60% of body weight, so solutes with a Vd 0.6L/kg distribute equally throughout total body water Vd <0.6 L/kg = restriction in the intravascular space Vd >0.6 L/kg = accumulation in extravascular compartments (ex. within fat)

Question 31

Extracorporeal therapies are most effective for solutes with what volume of distribution?

Answer 31

Low Vd (in the intravascular space)

Question 32

What are the main factors to consider when deciding on the best method of extracorporeal therapy?

Answer 32

The Vd, molecular weight, and percent protein binding of the solute you wish to remove

Question 33

What is the main determinant of whether a molecule can be removed via dialysis?

Answer 33

Molecular weight

Question 34

What occurs during TPE?

Answer 34

Solute separation is performed - a fraction of whole blood (plasma) is removed along with the molecules within that fraction Can remove solutes up to 1,000,000 Daltons that are highly protein bound molecules (>80% binding)

Question 35

When should extracorporeal therapy be recommended for toxin exposure?

Answer 35

- Toxin is likely to cause significant organ injury or death - Extracorporeal therapy is likely to exceed endogenous clearance (not useful for drugs with a very short half life) - Another antidote or treatment is not available

Question 36

What percent of dogs and cats require blood transfusions during hemodialysis?

Answer 36

Cats: 87% Dogs: 32%

Question 37

What factors are removed in TPE?

Answer 37

- Total proteins: 25% decrease - Fibrinogen: 53% decrease - Bilirubin: 36% decrease - BUN: 9% decrease

Question 38

What is the complication rate of TPE?

Answer 38

34% - transfusion reactions and signs of hypocalcemia (from citrate) most common