21 Renal Replacement Therapy: Dialysis Transplantation Flashcards Preview

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Flashcards in 21 Renal Replacement Therapy: Dialysis Transplantation Deck (19)
1

End stage renal disease (ESRD)

  • Definition
  • Incidence & prevalence
  • Causes
  • Treatment
  • Mortality
  • Economic costs

  • Definition
    • Permanent kidney failure requiring dialysis or transplant
  • Incidence & prevalence
    • > 600,000 ppl in the US
    • ~100,000 new pts per year
    • Rate of new cases: 4x higher in African Americans than whites.
  • Causes
    • DM
    • HTN
    • Glomerulonephritis
    • Cystic kidney diseases
  • Treatment
    • Hemodialysis (in-center, home) – 64%
    • Renal transplant– 30%
    • Peritoneal dialysis – 6%
  • Mortality
    • 7x higher for dialysis pts than general population
    • Transplant pts similar to non-ESRD pts
  • Economic costs 
    • $50 billion/yr
    • Largely covered by Medicare

2

Initiation of dialysis / renal replacement therapy

  • Indications
  • Goals
  • 4 elements of hemodialysis

  • Indications
    • A – Acidosis
    • E – Electrolyte abnormalities (esp hyperkalemia w/ EKG changes
    • I – Intoxications w/ water soluble drugs
    • O – Overload w/ salt & water that is refractory to diuretics & cardiac drugs & causes pulmonary edema, CHF, & HTN
    • U – Uremic symptoms including pericarditis, uremic bleeding, intractable nausea/vomiting, & anorexia
  • Goals
    • Remove uremic waste products & correct the secondary effects of uremia
    • Replenish calcium & bicarbonate stores
    • Remove excess water & salt
  • 4 elements of hemodialysis
    • Vascular access
    • Dialysis filter (dialyzer)
    • Dialysis solution (dialysate)
    • Dialysis machine to power and mechanically monitor the procedure

3

Removal of solute occurs primarily by diffusion

  • Diffusion rates are determined by...
  • The amount of diffusion that occurs is also dependent on...
  • Blood and dialysate flow
  • Low MW substances are dependent on...
  • High MW substances are dependent on...
  • Dialysate is composed of...

  • Diffusion rates are determined by...
    • Conc gradient of dissolved solutes on either side of the dialyzing membrane
    • Surface area and pore sizes of the dialyzing membrane
  • The amount of diffusion that occurs is also dependent on...
    • Dialysate delivery rate
      • ~500 mL/min of dialysate bathes the dialyzing membrane
    • Rate of blood flow pumped through the dialyzer
      • 300-400 mL/min, depending on the type of dialyzer & adequacy of the pt's access
  • Blood and dialysate flow
    • Opposite directions (countercurrent)  to maintain the conc gradient
  • Low MW substances are dependent on...
    • Flow rate 
  • High MW substances are dependent on...
    • Surface area and pore size
  • Dialysate is composed of...
    • Sodium 135-145 mEq/L
    • Potassium 0-4 mEq/L
    • Calcium 2.5-3.5 mEq/L
    • Magnesium 0.5-0.75 mEq/L
    • Chloride 98-124 mEq/L
    • Bicarbonate 30-40 mEq/L
    • Dextrose 11 mEq/L

4

Removal of solvent occurs primarily by ultrafiltration

  • Water molecule size
  • Water molecule movement
  • Convective transport

  • Water molecule size
    • Small enough that they pass freely between the blood and dialysate compartments
  • Water molecule movement
    • Driven in one direction by increasing the hydrostatic pressure gradient between compartments
    • Achieved practically by increasing resistance to blood flow as it leaves the dialyzer
  • Convective transport
    • Any molecules small enough will be carried with solvent (solvent drag)

5

Vascular access for hemodialysis

  • Arteriovenous (AV) fistulas
    • Primary or “native” AV fistula
    • Use
    • "Fistula first"
  • Synthetic AV fistulas (AV grafts)
    • Use
    • Construction
    • Adverse effects
  • Hemodialysis catheters
    • Temporary hemodialysis catetheters
    • Placed in...
    • Tunneled dialysis cathether (TDC)
    • Adverse effects
  • Access complications

  • Arteriovenous (AV) fistulas
    • Primary or “native” AV fistula: anastomosis between an artery and vein
      • Transmission of high arterial pressure into a low pressure venous system --> high flow AV fistula
      • Over time the vein “arterializes”: increases diameter & wall thickness
    • Optimal access for hemodialysis
      • Require 6 - 8 weeks to mature
      • Should be created 6 - 12 months before dialysis will be needed
    • “Fistula first”
      • National vascular access improvement initiative to support AV fistula placement in suitable hemodialysis patients, while reducing central venous catheter use.
  • Synthetic AV fistulas (AV grafts)
    • For pts w/ poor peripheral vasculature (diabetics) & insufficient venous size to allow the creation of a native AV fistula
    • Constructed of Polytetrafluoroethylene (PTFE)
      • Endothelialize in 2-3 weeks
      • This “maturation period” is necessary before they can be used.
    • Adverse effects
      • Higher rate of infection & clotting risk
      • Shorter lived than “native” AV fistulas
  • Hemodialysis catheters
    • Temporary hemodialysis catetheters
      • For 30 - 50% of pts w/ advanced chronic renal failure require immediate dialysis
    • Placed in the internal jugular vein (or subclavian vein or femoral vein)
    • Tunneled dialysis cathether (TDC)
      • Placed if dialysis is required for > 3 weeks & construction of an AV fistula isn't possible
      • Reduces the risk of infection
      • Avoid the subclavian site to reduce the risk of central venous stenosis
    • Adverse effects
      • Induction of venous stenosis
      • Poor flows
      • Thrombosis
  • Access complications
    • Thrombosis
      • --> obstruction of the access & poor blood flow
      • Outflow obstruction in an AV fistula --> localized extremity swelling
    • Infection
      • Local infections
      • Sepsis or septic emboli to bone, heart valves or the lungs
    • Steal syndromes
      • AV fistulas can reduce blood flow to the hand distal to the anastomosis --> ischemia, pain, & gangrene.
    • Cardiac overload
      • An AV fistula increases CO by 10% --> high output CHF

6

Hemodialysis prescription

  • Dialyzer
    • Type and size
  • Blood and dialysate flow rates
  • Duration and frequency
    • 3x/week (MWF or TTS) for 4 hrs each treatment
  • Dialysate composition
    • Typically adjust sodium, potassium, calcium, bicarbonate
  • Ultrafiltration
    • Can specify the amount of fluid to be removed
  • Anticoagulation
    • Usually heparin

7

Complications of hemodialysis

  • Acute intra-dialytic complications
  • Chronic complications
  • Dialysis survival rates

  • Acute intra-dialytic complications
    • May occur during any dialysis session
    • HoTN
      • Due to excessive ultrafiltration, autonomic neuropathy or peripheral vasodilation
      • Usually responds to normal or hypertonic saline or administration of colloid in the form of salt poor albumin (SPA) or mannitol
    • Cramps
      • Due to HoTN or inappropriately low dialysate Na conc
      • Usually responds to saline, quinidine sulfate, muscle relaxant, or carnitine
    • Nausea & vomiting
      • Due to HoTN or the disequilibrium syndrome (too brisk a reduction in uremic waste products, usually seen with initiation of dialysis)
      • Usually responds to correction of HoTN & anti-emetics
    • Access issues
    • To prevent disequilibrium syndrome
      • Less rigorous treatments at initiation of dialysis
      • Gradually increase dialysis parameters to most efficient settings
  • Chronic complications
    • Develop due to CKD & continue after dialysis started
    • Malnutrition
      • Best indicator of nutrition is serum albumin
      • Low albumin is a strong predictor of mortality
    • HTN
      • Treated w/ water & salt restriction & meds
    • Hyperlipidemia
      • Increased triglycerides & LDL w/ decreased HDL
    • Pruritus
      • Due to uremic toxins, elevated calcium-phosphorous product (>65), dry skin or allergies to components of the dialyzer or dialysate.
    • Mortality
      • Major cause of death is CV disease
    • Access issues
  • Dialysis survival rates
    • 80% at 1 yr
    • 50% at 3 yrs
    • 33% at 5 yrs
    • 10% at 10 yrs

8

Principles of peritoneal dialysis

  • Peritoneal dialysis definition
  • Peritoneal dialysis procedure
  • Peritoneal "dialysis" membrane
  • Water removal
    • Ultrafiltration
    • Forces affecting ultrafiltration
      • Osmotic gradient
        • Water movement
        • Major osmotic driving force in peritoneal dialysis
      • Hydrostatic pressure

  • Peritoneal dialysis definition
    • Fluid and solute exchange between the peritoneal membrane capillary blood and dialysis solution in the peritoneal cavity
  • Peritoneal dialysis procedure
    • Peritoneal membrane is used as a dialyzing membrane
    • Dialysate fluid is instilled into the abdomen & left for a period of time (dwell time) to absorb waste & remove fluid, then drained & discarded
    • Cycles / “exchanges” are repeated 4-5x/day
  • Peritoneal "dialysis" membrane
    • Vascular wall, interstitium, mesothelium & adjacent fluid films that make up the parietal and visceral peritoneal membrane
  • Water removal occurs by ultrafiltration
    • Ultrafiltration
      • Bulk movement of water through a semipermeable membrane
      • Osmosis = this ‘diffusion of water”
      • Due to the interaction of solvent molecules w/ dissolved solute, ultrafiltration --> solute transport via “solvent drag”
    • Forces affecting ultrafiltration
      • Osmotic gradient
        • Diffs in solute conc across a semipermeable membrane --> water moves from more to less dilute solution
          • Water flux will continue until the conc of osmotically active particles is equal on either side of the semipermeable membrane
        • Major osmotic driving force in peritoneal dialysis: supplied by dialysate glucose conc
          • Increase glucose conc --> increase ultrafiltration
          • This effect will dissipate as glucose is absorbed and as it is diluted out by water flux
      • Hydrostatic pressure
        • Causes some fluid movement
        • Plays a minor role in PD

9

Principles of peritoneal dialysis:
Diffusion rates of solute (electrolytes & uremic waste) removal are affected by...

  • Conc gradient of dissolved solutes on either side of the dialyzing membrane
    • Greater difference -->
    • Gradients are dependent on...
    • Dialysate conc is similar to hemodialysis sol'n except...
  • MW of the solute
  • Charge on the solute
  • Membrane resistances

  • Conc gradient of dissolved solutes on either side of the dialyzing membrane
    • Greater difference in solute conc b/n the 2 compartments --> more rapid flux of that solute from high to low conc
    • Gradients are dependent on the delivery rates of dialysate and peritoneal blood flow rate
      • Peritoneal blood flow is relatively constant even in shock
    • Dialysate conc is similar to hemodialysis sol'n except...
      • Substitution of lactate for bicarbonate
        • Ca bicarb will precipitate if bicarb is mixed w/ Ca-containing sol'ns)
      • Large dextrose conc (1.5 – 4.25 %)
  • MW of the solute
    • Larger MW --> slower it can move through membrane pores
  • Charge on the solute
    • Charged particles are hindered as they pass through the lipid bilayer
  • Membrane resistances
    • Peritoneal membrane can be altered by disease states
    • Acute peritonitis --> decreased membrane resistance & increased clearances
    • Repeated episodes of peritonitis --> scarring & slowed transport

10

Peritoneal dialysis:
Advantages & disadvantages

  • Advantages
    • Hemodynamic effects
    • Location
    • Process
    • Diet
    • Meds
  • Disadvantages
    • Efficiency
    • Infection
    • Requires...
    • Long-term
    • Can't be used in pts w/...
    • Can't be used for...

  • Advantages
    • Few hemodynamic effects
      • Method of choice in pts w/ a tenuous cardiac status
    • Done at home
      • Pts have greater freedom & independence for normal activities
      • Travel is easier
        • Supplies can be taken w/ the pt or delivered to the pt's destination.
    • Process is continuous
      • Pts are less likely to have disequilibrium syndromes seen in hemodialysis where clearance is efficient but episodic
    • Diet is more liberal
    • Meds (ex. insulin, antibiotics) can be administered in the peritoneal dialysis sol'n
  • Disadvantages
    • Gentler but less efficient form of dialysis
      • Dose may be inadequate in pts > 80 kg, who have lost residual renal function completely, or who are non-adherent with PD
    • Infection
      • Peritonitis due to poor technique: most common cause of transfer to hemodialysis
    • Requires compulsiveness & intellect
    • Pts on long-term PD can “burn out” due to the daily grind of doing their exchanges
    • Can’t be used in pts w/ peritoneal fibrosis or adhesions
      • Interferes w/ drainage
    • Can’t be used for > 1 week following abdominal surgery
      • Increases leaks at catheter site and infection

11

Peritoneal dialysis:
Peritoneal access

  • Standard access 
  • Procedure

  • Standard access
    • 2 cuff Tenckhoff style catheter
    • Made of silicone (catheter) & Dacron (cuffs)
    • Variety of dif catheters are available
  • Procedure
    • Catheter is inserted into the peritoneal cavity by a surgeon
    • Internal cuff is anchored in the muscle fascial layer immediately above the parietal peritoneum
    • Catheter is tunneled through the subcutaneous tissues & brought through the epithelium 5 - 10 cm lateral of where the internal cuff was seated
    • External cuff is usually 1 cm deep from the exit wound & causes local fibrosis, which seals the tunnel

12

Types of peritoneal dialysis

  • CAPD (Continuous Ambulatory Peritoneal Dialysis)
    • Procedure
    • Advantages
    • Disadvantages
  • CCPD (Continuous Cycler Peritoneal Dialysis) 
    • Procedure
    • Advantages
    • Disadvantages
  • Less common

  • CAPD (Continuous Ambulatory Peritoneal Dialysis)
    • Procedure
      • Instillation of 2 L of dialysate which dwells for 4 - 8 hours & then is drained
      • Repeated 4x/day
    • Advantages
      • Long dwell times--> max solute removal
      • Highest large solute clearances
      • Extremely portable.
    • Disadvantages
      • Manual exchanges  --> increased risk of infection
      • Constant fluid in the abdomen may worsen gastroparesis
  • CCPD (Continuous Cycler Peritoneal Dialysis)
    • Procedure
      • Pt connects to an automated peritoneal dialysis cycler at bedtime
        • Device periodically instills dialysate, allows it to dwell, then drains & replaces it in the pt's abdomen
        • 3-5 exchanges / nocturnal period
      • Machine instills a fresh aliquot of dialysate before the pt awakens & disconnects
        • Exchange dwells during the day
        • Daytime exchange is drained at bedtime when the pt connects to the machine
      • Advantages
        • Increased convenience by eliminating daytime exchanges
        • Decreased manual hook-ups--> decreased chance of peritonitis
      • Disadvantages
        • Short dwell times --> ineffective large molecule clearance
        • Requires excellent catheter function
          • Poorly draining PD catheter may not allow rapid cycling at night
        • Constant fluid in the abdomen may worsen gastroparesis
        • Being attached to a machine at night may interfere with sexual function
  • Less common
    • Combo of daytime exchanges & nocturnal cycling
    • Periods where the abdomen is “dry” (completely drained of fluid)

13

Complications of peritoneal dialysis

  • Mechanical
    • Intraluminal catheter occlusion due to fibrin 
    • Catheter occlusion due to a full colon (constipation) 
    • Catheter malposition or kinks
  • Dialysate leaks
  • Subcutaneous dialysate leaks
    • Past the internal cuff into the subcutaneous tissues 
    • Along the processus vaginalis 
  • Infections
    • Can involve...
    • Most torublesome PD infection

  • Mechanical
    • Intraluminal catheter occlusion due to fibrin
      • Occurs due to direct catheter irritation of the peritoneal membrane
      • Treatable w/ intraperitoneal heparin
    • Catheter occlusion due to a full colon (constipation)
      • Laxative treatment allows the catheter to reposition in the pelvic basin
      • In refractory cases, catheter replacement may be required
    • Catheter malposition or kinks
      • Requires catheter replacement
      • May be able to reposition w/ stiff wire under fluoroscopy
  • Dialysate leaks
    • Peritoneal-pleural dialysate leaks
      • Via large pores in the diaphragm --> pleural effusions
    • May require switch to hemodialysis
  • Subcutaneous dialysate leaks
    • Past the internal cuff into the subcutaneous tissues
      • --> soft tissue swelling
      • Resolves by allowing periods of time with a dry abdomen
      • May require new catheter
    • Along the processus vaginalis
      • --> swelling of the scrotum or labia major
      • Seen with inguinal hernias
      • Requires hernia repair or reinforcement of the internal ring of the inguinal canal
  • Infections
    • Can involve...
      • Peritoneal cavity (peritonitis)
      • Catheter tunnel (tunnel infection)
      • Exit site (exit site infection)
    • Most troublesome PD infection: peritonitis

14

Renal transplantation:
Process

  • Major problem
  • Patients w/ CKD are usually referred for transplant evaluation when...
  • Goal
  • Pt evaluation
    • Cardiac health
    • Malignancy screening
    • Infectious disease
    • HLA-typing or tissue typing
    • Social issues
  • Once the patient has successfully fulfilled these requirements...

  • Major problem
    • Lack of donor organs (17,000 transplants / 90,000 pts)
  • Patients w/ CKD are usually referred for transplant evaluation when...
    • Creatinine clearance < 20 ml/min
  • Goal
    • Transplantation before dialysis since post-operative management & graft survival is usually improved
  • Pt evaluation
    • Cardiac health
      • Cardiac disease is common in pts w/ CKD & is the leading cause of death in transplant recipients
      • Usually stress test + echo
    • Malignancy screening (ex.s)
      • Mammography for breast cancer
      • Prostate specific antigen for prostate cancer
      • Colonoscopy for colon cancer
    • Infectious disease
      • Screening for TB, hepatitis B or C, HIV, syphilis, & gonorrhea
      • Vital since immune suppressive therapy can increase the risk or severity of malignancy or an infectious disease
    • HLA-typing or tissue typing
      • To find the best “matched” kidneys for pts
    • Social issues
      • Pts w/ poor adherence to meds & current history of drug abuse won't be listed until they change their behavior
      • Evidence of coercion or financial reward of a potential donor is also grounds for refusing a recipient a transplant
  • Once the patient has successfully fulfilled these requirements...
    • Their name is entered on the transplant waiting list
    • Avg waiting time at UPMC: 3-5 years

15

Renal transplantation:
Surgery

  • Donor organs usually come from...
  • Operation

  • Donor organs usually come from...
    • Living donors (50%)
      • Living related donors (blood relatives)
      • Emotionally related donors (most commonly spouses)
      • ABO incompatible, + crossmatch
      • National kidney registry (NKR)
    • Brain dead or "deceased" donor (~7000/year)
      • SCD (standard criteria), ECD (expanded criteria), CDC high risk, DCD
  • Operation
    • Takes 3-4 hours
    • Incision along the inguinal ligament in right or left lower abdominal quadrant
    • Transplanted organ is anastomosed into the common, external or internal iliac artery and vein and the ureter connected to the bladder.
    • Pt is usually hospitalized for 5 days
    • Follow-up afterwards is intensive w/ daily outpatient visits for several weeks
    • If the transplant recipient does well, follow-up intervals progressively increase

16

Renal transplantation:
Outcomes

  • Life expectancy for grafts
    • Living donor
    • Deceased donor
  • % grafts surviving post-transplant
    • Living donor
      • 1 year
      • 5 years
    • Deceased donor
      • 1 year
      • 5 years
  • % pts surviving post-transplant
    • Living donor
      • 1 year
      • 5 years
    • Deceased donor
      • 1 year
      • 5 years

  • Life expectancy for grafts
    • Living donor: 15 years
    • Deceased donor: 10 years
  • % grafts surviving post-transplant
    • Living donor
      • 1 year: 95%
      • 5 years: 80%
    • Deceased donor
      • 1 year: 90%
      • 5 years: 66%
  • % pts surviving post-transplant
    • Living donor
      • 1 year: 98%
      • 5 years: 90%
    • Deceased donor
      • 1 year: 95%
      • 5 years: 80%

17

Renal transplantation:
Immunosuppressive agents

  • Corticosteroids
  • Calcineurin Inhibitors (cyclosporine A and tacrolimus)
  • Azathioprine
  • Mycophenolate
  • Sirolimus
  • Belatacept

  • Corticosteroids
    • Generalized suppression of the immune system
    • Prevent IL-1 and IL-6 production by macrophages
  • Calcineurin Inhibitors (cyclosporine A and tacrolimus)
    • Block interleukin-2 release from T cells
    • Prevent T-cell mediated lymphocyte proliferation
  • Azathioprine
    • Converts to 6-mercaptopurine
    • Inhibits DNA/RNA synthesis --> decreasing lymphocyte production
  • Mycophenolate
    • Inhibits inosine monophosphate dehydrogenase (IMPDH)
      • Essential rate-limiting enzyme in the purine metabolic pathway
      • Catalyzes the de novo synthesis of guanine nucleotides required for lymphocyte proliferation
    • Decreases B and T lymphocyte production
  • Sirolimus
    • Inhibits T-lymphocyte activation by suppressing IL-2 and IL-4 mediated proliferation
    • Inhibits B lymphocyte activity
  • Belatacept
    • Co-stimulatory blockade

18

Renal transplantation:
Post-transplant complications

  • Leading cause of death is cardiac
  • Second leading cause is infection
  • Malignancy, esp skin cancer and lymphoma
  • Recurrence of original glomerular disease
  • Chronic rejection & eventual graft failure

19

Renal transplantation:
Future directions

  • Xenografts
  • Stem Cells
  • Wearable Artificial Kidney (WAK)
  • Implantable Artificial Kidney

  • Xenografts
    • Transplanted organs from immunologically altered animals
    • Porcine sources are closest to human beings in size
    • Potential risks: introduction of infection or cancer causing agents from the animal source
  • Stem Cells
    • Could enable production of organs in vivo or in vitro
    • Science fiction at the present time
  • Wearable Artificial Kidney (WAK)
    • Miniaturized dialysis machine which can be worn like a belt
    • Allows pts to move about freely while undergoing uninterrupted dialysis treatment
    • Weighs 10 pounds & requires a couple of 9V batteries
  • Implantable Artificial Kidney
    • Thousands of nano-filters remove toxins from the blood
    • A BioCartridge of renal tubule cells mimics the metabolic and water-balance roles of the human kidney
    • Relies on the body's BP to perform filtration w/o needing pumps or an electrical power supply
    • Not ready for clinical trials for another 5-7 years