Renal transplant and renal replacement therapy Flashcards
What is the ideal feline renal allograft recipient?
A cat with significant, compensated CKD that is otherwise healthy
When should renal transplantation be performed?
Controversial - some centers use a minimum creatinine of 4.0 mg/dL as a cutoff
What disease conditions rule out a cat for transplantation and should be tested for?
FIV, FeLV, moderate to severe heart disease, neoplasia, pyelonephritis, other significant comorbities (Toxoplasmosis, etc)
What disease conditions should be tested for and addressed before transplant?
Systemic hypertension, hyperthyroidism, active infections, periodontal disease
During transplantation, warm ischemic time of the donor kidney should be limited to how long?
<60 minutes
The donor kidney can be flushed with what solution to store for up to 7 hours before transplantation?
Cold sucrose phosphate solution
What drugs are used for immunosuppression post-operatively?
Cyclosporine and prednisolone
Cyclosporine absorption varies among cats. How often should cyclosporine levels be monitored post-operatively?
Weekly until the right dose is identified, then every 3 months
What complication has been reported acutely after renal transplantation and is associate with neurologic signs (60% of cats in one study)?
Severe hypertension (>170 mmHg)
What drug can be used to mitigate post-transplant hypertension?
Hydralazine
What is delayed graft function?
- Lack of function in an allograft with otherwise normal blood flow and no evidence of obstruction
- Creatinine >3 for 3 days after transplantation
What causes delayed graft function?
Pre-, peri-, or intraoperative graft injury
What are clinical signs of an acute graft rejection?
Palpable enlargement of the allograft, hyperthermia or hypothermia, malaise, loss of appetite, weight loss, worsening azotemia
How is an acute rejection reaction treated?
IV immunosuppressives and fluid therapy until creatinine plateaus
What is chronic allograft nephropathy?
Chronic, gradual loss of allograft function characterized by interstitial fibrosis and tubular atrophy
What percent of feline allografts have evidence of chronic allograft nephropathy on histopathology?
70%
What percent of renal transplant patients develop infections?
25-36%
Following renal transplantation, what is the increased risk of cancer compared to age matched controls?
6 fold increase in cancer risk
What is the 6 month survival rate for cats undergoing renal transplantation? 3 year survival rate?
6 month: 60-65%
3 year: 40%
What is the median survival time of dogs after renal transplant?
Terrible 24 days in one study, 8 months in another study
What percent of feline donors for renal transplant have no long term effects? What percent develop renal insufficiency? Die from urinary tract disease?
- 84% had no long term effects
- 5% developed CKD (2 died)
- 2% developed AKI
- 4% developed acute ureteral obstruction and died
What are the indications for renal replacement therapy (RRT) in dogs and cats?
- Anuric or severe oliguric AKI
- Refractory life threatening hyperkalemia
- Refractory hypervolemia
- Severe or progressive azotemia (>5)
How is diffusion used in hemodialysis? What molecular weight molecules can it remove? Name 2 molecules that are removed via diffusion
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
What is the equation for diffusion flux in hemodialysis?
Diffusion flux = -KoA x C
Ko: mass transfer coefficient (membrane permeability)
A: membrane surface area
C: concentration gradient
What is convection and how is it used in hemofiltration? What size molecules can be removed?
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
What is ultrafiltration?
Movement of water across a semipermeable membrane
What is adsorption and how is it used in hemoperfusion? What types of molecules can it remove?
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
Compared the sizes and protein binding of molecules removed via hemodialysis, hemofiltration, hemoperfusion, and TPE
What are 2 major determinants of dialysis disequilibrium?
Degree of azotemia
Rate of solute removal
What is volume of distribution and what do the values indicate?
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)
Extracorporeal therapies are most effective for solutes with what volume of distribution?
Low Vd (in the intravascular space)
What are the main factors to consider when deciding on the best method of extracorporeal therapy?
The Vd, molecular weight, and percent protein binding of the solute you wish to remove
What is the main determinant of whether a molecule can be removed via dialysis?
Molecular weight
What occurs during TPE?
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)
When should extracorporeal therapy be recommended for toxin exposure?
- 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
What percent of dogs and cats require blood transfusions during hemodialysis?
Cats: 87%
Dogs: 32%
What factors are removed in TPE?
- Total proteins: 25% decrease
- Fibrinogen: 53% decrease
- Bilirubin: 36% decrease
- BUN: 9% decrease
What is the complication rate of TPE?
34% - transfusion reactions and signs of hypocalcemia (from citrate) most common
