5. Chronic kidney disease management: dialysis, transplantation

Question 1

What is the place of RRT in the treatment of CKD?

Answer 1

• It doesn’t replace all aspects of renal function. It primarily supplies clearance. Other aspects of CKD (anemia, renal bone disease, acidosis) need to be treated medically.
• You start dialysis at about 8-10ml/min mean GFR
• The best form of RRT is kidney transplantation, but it involves major surgery and is not always successful. On the other hand, dialysis can maintain stability but has many complications
• For some patients, no form of RRT is acceptable and thus conservative management is required (very elderly or significant comorbidities)
  
  • Symptom control + delaying progression

Question 2

What are the types of RRT?

Answer 2

• Kidney transplantation
• Dialysis:
  
  • Hemodialysis
  • Hemofiltration
  • Peritoneal dialysis

Question 3

What are the indications for dialysis?

Answer 3

• Life threatening AKI
• Progressive CKD
• ESRD with GFR < 15ml/min (GFR < 20ml/min if DM)
• Resistant hypervolemia
• Resistant hyperkalemia
• Resistant acidosis
• Uremic encephalopathy or pericarditis
• Intoxications (e.g. ethyl glycol, methanol, lithium)

Question 4

What is the mechanism of hemodialysis?

Answer 4

Diffusion (“tea bag”):

• Blood is passed over a semi-permeable membrane against dialysis fluid flowing in the opposite direction (countercurrent), thus blood is always meeting a less concentratated solution and we have diffusion of small solutes down the concentration gradient throught the membrane.
• Ultrafiltration creates a negative transmembrane pressure and used to clear excess fluid
• No medical contraindication

Convective transport (“coffee”) - Osmosis:

• The solvent drag of toxins

Question 5

How often is hemodialysis indicated and what are the preparations? What are the drawbacks?

Answer 5

• 3x/week for 4 hours in dialysis center
• Arteriovenous fistula in the radial artery and cephalic vein
• OR, tunnelized catheter in a large veins (IJV)

Drawbacks:

• Vascular access may result in thrombosis, stenosis, steal sydnrome, infection, blockage and recirculation of blood
• Disequilibration syndrome (cerebral edema during or shortly after hemodialysis)
• Hypotension
• Time consuming
• Expensive

Question 6

What is hemofiltration?

Answer 6

• It is hemodialysis with extra fluid and with a highly permeable membrane ==> diffusion of large and small solutes
• The ultrafiltrate is replaced by an equivalent volume of fluid thus there is no hemodynamic instrability
  
  • It is used in critically ill patients for this reason, but impractical in the long term as it takes much longer than hemodialysis to achieve the same clearance

Question 7

What is peritoneal dialysis and its preparation?

Answer 7

• A Tenckhoff catheter is inserted into the peritoneum, which works as a semi-permeable membrane
• Ultrafiltration is achieved by using glucose as an osmotic agent (convective transport)

Question 8

How often is peritoneal dialysis indicated and how? What are its drawbacks? Contraindications?

Answer 8

• 4x/day for 30 min
• Can be done at home, alone ==> more freedome
• Least expensive methode

Drawback:

• Peritonitis
• Exit site infection
• Loss of membrane function over time
• Hemorrhage

Contraindications:

• Uncorrected abdominal hernia
• Abdominal stoma
• Previous abdominal surgery
• Obesity
• Poor compliance and personal hygiene
• Anuria

Question 9

What is the comparison between hemodialysis and peritoneal dialysis?

Answer 9

• Hemodialysis if more common in the western world, but requires more time as the patient has to go to dialysis center 3x/week for 4 hours
• Peritoneal dialysis allows more freedom and flexibility, but risk of infections.
• Both have the same life expectancy

Question 10

What are the complication of RRT?

Answer 10

• Annual mortality is 20% mostly due to CV disease (MI, CVA) perhaps due to combination of HTN and calcium/phoaphate dysregulation
• Protein-calorie malnutrition is common in hemodialysis an associated with morbidity and mortality
• Renal bone disease (high bone turnover): renal osteodystrophy, osteitis fibrosa
• Infection: uremia causes granulocyte dysfunction
  
  • Sepsis-related mortality increased by 100-300 fold
• Amyloid accumulation in the long-term with dialysis patients and may cause carpal tunnel syndrome, arthralgia and fractures
• Malignancy is more common in dialysis patients
  
  • May be related to ESRD

Question 11

What are the implications of kidney transplantation?

Answer 11

• Treatment of choice in ESRD
• Major surgery with long immunosuppression with a lot of potential complications
  
  • Patients need to be psychologically suitable for it
• Anesthetic assessement is the key as well as cardiac testing and investigation of ther systems (respiratory)

Question 12

What are the allocations of kidney transplantation?

Answer 12

Prerequisite:

• Blood group compatibility (only ABO, Rh doesn’t matter)
• Negative crossmatch (to avoid host versus graft)

Matching:

• HLA
• Urgency, immunization status, age, gender

Question 13

What are the absolute contraindications of kidney transplantation?

Answer 13

• Active infection
• Cancer (if > 5years ago and considered cured, it may be considered for transplant)
• Severe comorbidities

Question 14

What are the different types of graft?

Answer 14

• Donor after cardiac death:
  
  • Donors who don’t meet criteria for brainstem death. Retrieval of organs only begins when CO has ceased
  • High risk of delayed graft function due to long warm ischemic time
• Donor after brainstem death:
  
  • ​Braindead patients that remain on cardiorespiratory support for retrieval
  • Much lower risk of delayed graft function
• Live donor:
  
  • Grafts give much better outcomes with planned surgery and minimal ischemic time
  • Related or unrelated donors
  • All need a psychological assessement to make sure they understand the risks

Question 15

What type of immunosuppression is required in kidney transplantation?

Answer 15

• Induction:
  
  • Conventional induction through anti-IL2 receptor monoclonal antibody (basiliximab or alemtuzumab)
    
    • Provides broad immunosuppression and allows steroid-free maintenance regimen
• Maintenance:
  
  • ​Mostly on triple therapy
    
    • Calcineurin inhibitor (CNI, tacolimus, cyclosporine)
    • Antimetabolite (azathioprine, mycophenolate)
    • Prednisolone

Question 16

What are the complications of kidney transplantation?

Answer 16

• Surgical:
  
  • Bleeding, thrombosis, infection, urinary leaks, lymphocele, hernia
• Recurrent or de novo kidney disease
• Delayed graft function:
  
  • Up to 40% of grafts especially in DCD
  • Usually due to ATN in graft
• Rejection:
  
  • Acute:
    
    • Humoral-mediated or cellular-mediated (more common)
    • High IV dose of methylprednisolone and intensification of immunosupression is required
  • Chronic allograft nephropathy:
    
    • Combination of chronic, low-grade antibody response + vascular changes and the effect of calcineurin inhibitor
    • Usually doesn’t respond to treatment, but slowed progression when switching from CNI to sirolimus
• Infection:
  
  • _​_Increased risk of any infection by opportunistic pathogens (E.g. HSV, candid, pneumocystis jirovecii, CMV, HBV)
• Malignancy:
  
  • ​5-fold increased risk of cancer due to immunosuppression, espcially in the skin and viral-associated (HPV, EBV)
• Cardiovascular disease:
  
  • Probably due to drugs.
  • Leading cause of death in transplant patients
    
    • HTN in > 50% of transplants (probably due to donor vascular disease in graft + immunosuppression)

Question 17

What is the prognosis of kidney transplants?

Answer 17

• 1 year survival:
  
  • Graft: 91% (DCD) to 96% (LD)
  • Patient: 96% (DCD) to 99% (LD)
• 10 year survival:
  
  • Graft: 60% (DCD) to 80% (LD)