Lecture 21 - Dialysis

what is diffusion

passive movement of solutes from an area of higher concentration to an area of lower concentration until an equilibrium is reached

what is ultrafiltration

process that removes excess fluid from blood during dialysis, relies on pressure differences across a semipermeable membrane

fluid moves from higher to lower fluid pressure gradient 

what is ultrafiltration driven by in hemodialysis

hydrostatic pressure 

what is ultrafiltration driven by in peritoneal dialysis

osmotic pressure 

what is convection

passive movement of solutes dissolved in fluid from pressure gradients rather than differences in concentration (solvent drag)

solutes move from area of higher to lower fluid pressure gradient

rate is dependent on molecular size

what principles does hemodialysis use

diffusion

ultrafiltration

limited convection

what principles does peritoneal dialysis use

diffusion 

ultrafiltration

convection 

what is hemodialysis

blood flows counter-current with dialysate

blood and dialysate are separated by semipermeable membrane → allows for movement of fluid and solutes from blood to dialysate

what is peritoneal dialysis

dialysate is infused into peritoneal cavity

blood and dialysate are separated by peritoneal membrane → acts as semperimeable membrane and allows for movement of fluid and solutes from blood to dialysate

what does the rate of movement of solute depend on 

concentration gradient

permeability of membrane 

surface area of membrane 

length of time that blood and fluid remain in contact with membrane

what are the indications for dialysis in AKI

Acidosis - metabolic acidosis

Electrolyte abnormalities - hyperkalemia

Intoxications - salicylates, lithium, methanol, ethylene glycol, theophylline, phenobarbital

Overload - fluid overload

Uremia - pericarditis, encephalopathy

what are the goals of therapy for dialysis in AKI

maintain fluid and electrolyte, acid-base, and solute hemostasis

prevent further injury to kidney

permit renal recovery

allow other supportive measures

when should dialysis be considered in CKD

patients with GFR <15-20 or risk of renal replacement therapy >40% over 2 years → referred to specialist

balance between prolonging the dialysis-free period to maximize quality of life while trying to facilitate a dialysis-assisted period with minimal complications

should dialysis be initiated early in CKD

no - does not appear to increase survival in CKD patients

early start is associated with increased mortality in patients without diabetes or other comorbidities

starting dialysis at eGFR 14-16 may be associated with 5% reduction in 5 year risk of death (extend life by 1.6 months) compared to starting at eGFR 6-7

when should dialysis be initiated in CKD

if one or more of the following are present:

• s/s of kidney failure - neurological attributed to uremia, pericarditis, anorexia, medically-resistant acidosis/electrolyte abnormalities, intractable pruritus, serositis

• inability to control volume status or BP

• progressive deterioration in nutritional status refractory to dietary intervention 

• cognitive impairment 

initiated based on clinical status rather than specific CrCl (s/s manifest around eGFR 5-10)

what are the goals of therapy for dialysis in end-stage CKD

manage s/s of ESRD

remove uremic toxins and other substances

restore fluid and electrolyte imbalances

re-establish normal pH

what are properties of hemodialysis

most common renal replacement therapy for ESRD

extracorporeal - cleaned outside body

membrane is artificial

can be done in centre or at home

how does hemodialysis clean blood 

dialysis machine pumps blood from body towards semipermeable membrane 

• blood flows counter-current to dialysate (creates larger conc. gradient)

• membrane pores allow movement of small molecules, but not large enough for RBCs

solutes removed from blood by diffusion → creatinine, potassium, urea, uremic toxins, drugs 

excess water removed by ultrafiltration 

bicarbonate moves from dialysate to blood 

limited convection 

what are the main components of a hemodialysis circuit

vascular access

dialyzer

dialysate

dialysis machine

when is temporary access used for hemodialysis

immediate access required

done via central venous catheter (CVC)

when is permanent access used for hemodialysis 

advanced planning 

done in arteriovenous (AV) fistula or graft 

where is a central venous catheter inserted for hemodialysis

large vein e.g. jugular, subclavian, femoral

what is an AV fistula

preferred method for permanent access HD

native fistula: surgically created by connecting an artery and vein in the forearm

require 2-6 months for maturation before it can be used for HD

longest survival time of vascular access methods and lower rate of complications

what is an AV graft 

synthetic tubing graft is surgically inserted under the skin to connect an artery and a vein 

require 2-4 weeks of healing time before it can be used for HD

shorter access survival time, higher rates of infection and thrombosis  

what is the dialyzer in HD

filter, artificial kidney

houses semipermeable membrane

• larger pores = increased diffusion of solutes

• more permeable to water transport = increased ultrafiltration of water

blood flows through one section and dialysate through the other

what is the dialysate in HD

cleasing fluid, contains electrolytes, purified water, dextrose

composition can be adjusted based on patient needs

bicarbonate - high concentration allow for movement of bicarbonate into blood

potassium - low concentration to prevent sudden hypokalemia as excess potassium is removed from blood

what does the dialysis machine do in HD 

monitors patient for dry weight and BP

controls flow rates or blood and dialysate 

controls ultrafiltration 

what is a typical in-centre HD schedule

3x/week with each HD run lasting approx. 4 hours

what is a typical home HD schedule 

interval and duration of HD

• 3-6x/week

• some patients can do nocturnal HD

what are complications during HD

hypotension

HTN

cramps

N/V

headache

chest/back pain

pruritis

fever/chills

what are infectious complications of HD

access site infections

bacteremia, sepsis

what are non-infectious complications of HD

worsening of existing anemia

thrombosis of AV fistula/graft/catheter 

what are advantages of dialysis 

higher solute clearance - intermittent treatment 

clear parameters → underdialysis detected early

low technique failure rate 

homeostasis parameters better corrected than in peritoneal dialysis 

close monitoring in centre

what are disadvantages of dialysis

multiple visits per week

disequilibrium, hypotension, muscle cramps are common

infections/thrombosis

decline in residual kidney function more rapid compared to peritoneal dialysys

what is the process of peritoneal dialysis

instillation of dialysate into the peritoneal cavity through the PD catheter

peritoneal membrane = semipermeable membrane between dialysate and blood → abdominal viscera is highly vascularized

solutes are removed from blood across peritoneal membrane by diffusion and convection (solute drag)

excess plasma water removed by ultrafiltration

what are the components of PD

1. access → permanent PD catheter 

2. dialyzer → peritoneum semipermeable membrane

3. dialysate → PD bag solutions, osmotic agent is dextrose, similar electrolyte composition to serum but no potassium, uses lactate instead of bicarbonate

what are contraindications of PD

absolute: peritoneal adhesions from previous surgeries

relative:

• ostomy

• severe physical or mental disability

• inflammatory bowel disease

• lack of appropriate caregiver or inadequate living situation for home dialysis

what exchanges occur in PD

fill → dialysate solution is instilled into the peritoneal cavity (20 mins)

dwell → duration dialysate remains in peritoneal cavity (2 hours)

drain → effluent fluid removed from peritoneal cavity (10-15 mins)

whole process called an exchange

what factors are considered when determining a PD prescription

types → continuous ambulatory PD or automated PD

target dry weight

number of exchanges per day

volume of dialysate to be instilled for each exchange

type of dialysate (dextrose concentration)

dwell duration

what are infectious complications of PD

PD peritonitis → infection within peritoneal cavity 

PD catheter exit site infections 

tunnel infections 

what are non-infectious complications of PD

increased glucose absorption from dialysate → hyperglycemia, increased insulin requirements, hypertriglyceridemia, weight gain, obesity

malnutrition (loss of albumin)

fibrin formation in dialysate

hypokalemia

what are advantages of PD

slow filtration = hemodynamic stability

high clearance of large solutes

better preservation of kidney function

convenient route for drugs like ABX or insulin

freedom from the machine = independence

less blood loss/iron deficiency

no systemic heparization

what are disadvantages of PD

loss of proteins and amino acids

risk of peritonitis

infections

inadequate ultrafiltration with large body size

high rate of technique failure

obesity

hernias, dialysate leaks, hemorrhoids, back pain

what are trends in morbidity and mortality in patients on dialysis 

increased hospitalizations and complications 

lower life expectancy → 40% 5 year survival

leading causes of death: CV related causes, infections

mortality rates steadily declining 

what are impacts of dialysis on quality of life

physical endurance

employment

social life

diet

sex

fatigue

high rates of depression and anxiety

what is the role of the pharmacist in dialysis patients

drug dosing → drug dialyzability, dose adjustments, timing of medications

de-prescribing of nephrotoxic drugs

medication education

management of CKD complications

PD patients → management of constipation, peritonitis

HD patients → management of hypotension

what is drug dialyzability 

how much drug is removed from body during dialysis

high = more removed

low = less removed 

depends on molecular weight, protein binding, Vd, water solubility, dialysis membrane, blood/dialysate flow rates 

what are the general principles of drug dosing in dialysis

renally cleared drugs → dose adjustments

if drug is unaffected by renal impairment (>50% elimination by other routes), typically no adjustments needed

drugs that are toxic and excreted in active form → dose or frequency adjustment to avoid accumulation

drugs highly dialyzed → dosing adjustments, adjust timing (post-dialysis), may require supplementary dosing