JC77 (Medicine) - Renal replacement therapy Flashcards
Renal replacement therapy 3 main types? When to start?
Peritoneal dialysis Hemodialysis Kidney transplantation
Start when:
- GFR falls to <10mL/min/1.73m3
- Uremic symptoms
Mechanism of peritoneal dialysis
Diffusion
- Process where molecules in solutions diffuse across semipermeable membrane using a concentration gradient
- Pulls solutes out of blood from peritoneal capillary network through membrane into intraperitoneal dialysate
- MOST effective for molecules that are not present in dialysis including urea, creatinine, K+, PO43- and other uremic toxins
Ultrafiltration
• Convective process where molecules pass through pores in the membrane using hydrostatic or osmotic pressure gradients
• Occurs across osmotic pressure gradient between dialysate and blood created by adding dextrose, icodextrin (glucose polymer solution) to dialysate
Factors that influence choice between peritoneal dialysis and hemodialysis
- Contraindications to PD or HD
- Local healthcare reimbursement - PD cheaper, used first
- Patient preference - PD at home or HD in hospital
Peritoneal dialysis
Indications
Contraindications
Indications:
- Acute kidney injury
- Chronic kidney injury with GFR < 10 mL/min/1.73 m2 (OR) Stage 5 CKD (AND) uremic symptoms
Contraindications:
Previous extensive abdominal surgery (scarring)
Frequent PD-related peritonitis
Place of residence that does not permit peritoneal dialysis or residence lacking sanitary conditions
Peritoneal dialysis
Subtypes
Continuous ambulatory peritoneal dialysis (CAPD)
Automated peritoneal dialysis (APD):
- Continuous cycling peritoneal dialysis (CCPD)
- Nocturnal intermittent peritoneal dialysis (NIPD
Explain why the peritoneal membrane is chosen for dialysis
- Thin semipermeable membrane
- Large surface area
- Highly vascularized
3 components of peritoneal dialysis
Peritoneal membrane
Peritoneal dialysis catheter
Peritoneal dialysis fluids
Peritoneal cavity access for PD
- Name of catheter
- Insertion and exit site
- Placement inside cavity
Tenckhoff catheter: with many side holes and 2 fibrous cuffs
Insertion: Paramedian incision is created, insertion ≥ 2 weeks before start of dialysis
Exit: Lateral and caudal to entrance site, should be visible by patient and should not be located at the belt line, skin creases or skin folds
Placement: Tip should be pointing downwards inside pelvic cavity since the pelvis is the most dependent part of the body
Typical composition of peritoneal dialysis fluid
Balanced salt solutions with
- No Potassium
- Glucose as osmotic agent: in 1.5/ 2.5/4.25g per dL concentration for various osmotic strengths
- Lactate as buffer agent
- Salts: Sodium, Calcium, Magnesium, Lactate
Compare the timing between different types of peritoneal dialysis
Continuous ambulatory peritoneal dialysis (CAPD): Manual, multiple exchanges (3 times) during daytime + overnight dwell
Automated:
Continuous cycling peritoneal dialysis: Full 24 hour cycle
Nocturnal intermittent peritoneal dialysis: Only at night, with faster dwells
Compare CAPD and APD
- Timing of PD exchange
- Need for daytime exchange
- Dialysis efficacy
- QoL
- Cost
4 types of osmotic agents in peritoneal dialysis solution
Glucose/ Dextrose: Most common, concentrations including 1.5% (小水)/ 2.5% (中水)/ 4.25% (大水)
Low GDP solution
Glucose-polymer-containing solution (Icodextrin*): Reduced carbohydrate dose provides some long-term metabolic advantages, good for DM
Amino-acid based solution: Improves nutritional status in PD patients
Disadvantages of using dextrose as osmotic agent in peritoneal dialysis solutions
- Easily absorbed leading to short-lived ultrafiltration
- Leads to metabolic complications including metabolic syndrome (hyperglycemia + hyperlipidemia + weight gain)
- Presence of glucose degradation products (GDP) which affects peritoneal host defence mechanism by inhibiting phagocytosis and bactericidal activity
Reasons for different salts and ions additives in peritoneal dialysis solution
Replenish low ions:
- Mg
- Ca
Avoid worsening electrolyte imbalance
- No Potassium (Patients are usually hyperkalemic, aim serum K+ at 4mEq/L)
- Low Na prevents hyperNa due to fluid removal
Complications of peritoneal dialysis
Catheter:
- Pericatheter leakage
- Bleeding, Injury to visceral organs
- Mechanical flow dysfunction: catheter failure, kinking, malposition
- Dialysis Failure
- Catheter migration
Catheter-associated infections:
- Exit site infections
- Tunnel infections
Metabolic:
- Metabolic syndrome (Hyperglycemia + Hyperlipidemia + Weight gain)
- Hypoalbuminemia
PD-related peritonitis
- Causative pathogens
- Predisposing factors
Microbiology:
o Gram +ve: Staphylococcus sp. (Particularly coagulase -ve)
o Gram -ve: E. coli/ Campylobacter/ Pseudomonas aeruginosa
o Mycobacterium tuberculosis
o Fungal infections
Predisposing factors:
- Catheter-associated infection (exit-site and tunnel infections)
- Contamination of catheter during exchange
- Underlying GI pathology (cholecystitis/ appendicitis/ diverticulitis)
- Constipation or diarrhea
- Recent invasive interventions (colonoscopy/ cystoscopy/ hysteroscopy)
PD-related peritonitis
Diagnostic tests
Treatment
Diagnostic:
- Clinically features indicative of peritonitis such as fever, abdominal pain or cloudy effluent
- WBC count ≥ 100 cells/mm3 and percentage of neutrophils (PMNs) > 50% in peritoneal fluid after dwell time ≥ 2 hours
- +ve Peritoneal dialysate effluent culture
Treatment:
- Gram +ve: 1st generation cephalosporin (cefazolin) or Vancomycin
- Gram -ve: Aminoglycoside or 3rd or 4th generation cephalosporin (ceftazidime/ cefepime)
- Cover both: e.g. Cefazolin + Amikacin
- Remove catheter for recurrent infections
Peritoneal dialysis failure
Cause
Chronic exposure to dextrose in PD fluid, Repeated peritonitis >> Fibrosis of peritoneal membrane and marked thickening of membrane
Peritoneal dialysis catheter leakage
Possible cavities involved
Leak out of peritoneal cavity to:
Pleural cavity
Anterior abdominal wall
Retro-peritoneal space
Main components of hemodialysis
Vascular access:
- Arteriovenous fistula (AVF)
- Arteriovenous Graft (AVG(
- Tunneled cuffed double lumen central venous catheter
Hemodialysis machine
Hemo-dialyzer
Choice of vascular access for chronic hemodialysis?
Reasons?
AV fistula most preferred
AV fistula > AV graft > Central hemodialysis catheter
Reasons:
lowest morbidity and mortality, lowest need for intervention and best long-term patency
Central hemodialysis catheter for HD
Risks
Indications
Risks: worse complication and survival rates than AV fistula or AV graft
Indications:
o AV access is exhausted
o AV access is contraindicated (e.g. severe heart failure)
o Expected duration of dialysis < 1 year
Compare AV fistula with AV graft
- Likelihood of failure
- Long-term patency
- Time to mature
- Ease of cannulation
- Complication rate
List 2 types of hemodialysis
Compare:
- frequency
- Duration
- Efficacy
- QoL
- Cost
- Training
Types of AV fistula and AV graft
AVF: vein-to-artery anastomosis
- Radial-cephalic AVF
- Brachial-cephalic AVF
- Brachial-basilic AVF
AVG: Constructed by interposing a prosthetic graft between an artery and vein with expanded polytetrafluoroethylene (ePTFE)
- Looped forearm (Brachial artery to cephalic vein)
- Straight forearm (Radial artery to cephalic vein)
- Looped upper arm (Axillary artery to axillary vein
- Straight upper arm (Brachial artery to axillary vein)
Complications of hemodialysis
Vascular access, catheter-related, dialysis-related complications
Vascular access:
Stenosis, thrombosis, upper limb ischemia
Catheter access:
Exit site infection, Bacteremia, Catheter malfunction (clot)
During dialysis:
CVD: hypotension, arrhythmia
Neuromuscular: Muscle cramps
Technical: Air embolism, blood loss
Central vascular access for HD
Which veins are used?
Internal jugular vein (IJV) (most common)
o Right IJV is preferred since it takes a straight path into SVC
External jugular vein (EJV)
Common femoral vein
o Indicated in bilateral occlusion of central thoracic vein
Subclavian vein
o Indicated if internal and external jugular veins are occluded and common femoral vein is not a good option
MHC
Genes contained in Major Histocompatibility complex
Expression of genes in MHC
- MHC Class I: HLA-A,B,C - Present on all nucleated cells and platelets
- MHC Class II: HLA-DP,DQ,DR - Expressed on APCs (antigen presenting cells)
- MHC Class III: TNF, C4 - Does not code for HLA but contains genes for other components involved in inflammation and other immune complexes
HLA genes
Function
Inheritance
Variability
HLA genes are blueprints to show how cells should organized amino acids to make proteins and are located on chromosome 6
Inheritance:
Each person gets two copies of each gene, one from father and one from mother
4 possible combinations from parents to children
Variability: highly polymorphic
Individual can express 6 different types of MHC Class I molecules and 6 different types of MHC Class II molecules on the cell surface
Reason for HLA matching before renal transplant
Matched HLA antigens at serological level required including HLA-A, HLA-B and HLA-DR
Anti-HLA antibodies will target against HLA antigens expressed on surface of allograft
Crossmatch is performed prior to transplantation to evaluate for any evidence of preformed antibodies with specificity for the potential donor that could lead to hyperacute or acute antibody-mediated rejection (AMR)
Pre-requisites for living and deceased donor for renal transplant
Requirements for living donor
• Good past health
• Normal renal structure and function
Requirements for deceased donor
• Irreversible brain damage leading to brainstem death
• Normal renal structure and function
• No known history of kidney disease
• No known history of long-standing HT or DM
Patient pre-requisites for renal transplant
Acute kidney injury (AKI)
• A = Acidosis: Metabolic acidosis with HCO3- < 10 mmol/L
• E = Electrolyte disturbance: Uncontrolled hyperkalemia > 6 mmol/L
• I = Intoxication
• O = Oedema: Fluid overload/ Uncontrolled pulmonary edema
• U = Uremia: Uremic pericarditis/ Uremic encephalopathy/ Intractable uremic symptoms
Chronic kidney disease (CKD)
• Patients with GFR < 10 mL/min/1.73 m2 (OR) Stage 5 CKD
• Patients becomes symptomatic of uremia
List uremic symptoms
Does it correlate with serum BUN or creatinine?
anorexia, nausea, vomiting, pericarditis, peripheral neuropathy and CNS abnormalities such as loss of concentration, lethargy, seizures and coma
NO direct correlation exists between the absolute serum levels of blood urea nitrogen (BUN) or creatinine and the development of symptoms
Nephrectomy techniques for renal transplantation
- Laparoscopic nephrectomy for living donor
- Open nephrectomy for deceased donor
Implantation of renal allograft
- Incisions
- Indications for removal of native kidney(s)
- Locations for placement of allograft
Incisions:
- Gibson incision - Curvilinear incision in the lower quadrant of the abdomen
- Hockey stick incision- Inverted J-shaped incision
Indications for removal of native kidneys:
- Renal cell carcinoma (RCC)
- Polycystic kidney disease (PKD)
- Pyelonephritis
Placement:
- Right iliac fossa (RIF)
- Extraperitoneal (retroperitoneal) position
Renal transplantation
3 Anastomosis
Renal artery (donor) anastomosis to internal or external iliac artery (recipient)
Renal vein (donor) anastomosis to external iliac vein (recipient)
Anastomosis of ureter to the bladder by ureteroneocystostomy
Methods to monitor renal allograft function
Serum creatinine and GFR
Urine dipstick (Urinalysis) for proteinuria/ Spot urine albumin-to-creatinine ratio (ACR)
Allograft renal biopsy (if allograft dysfunction)
Types of organ rejection after transplantation according to timing
Hyperacute (7mins) - Pre-existing antibodies and complement activation to donor tissue
Acute (8-11 days) - CD4-controlled, CD8 mediated, NK cells and macrophage-mediated
Chronic rejection (3 months to 10 years) - Mixed CD4 and antibody
Short-term/ acute complications of renal transplant
Acute transplant rejection
Side-effects to Rejection prophylaxis drugs
Rejection prophylaxis in renal transplant
Purpose
Choice of prophylaxis drugs
Long-term immunosuppressant is needed to prevent rejection of transplanted kidney by recipient’s immune system
3 immunosuppressants are used concurrently to minimize the side effects of individual drugs while achieving adequate immunosuppression
• Corticosteroids (e.g. Prednisolone) (AND)
• Calcineurin inhibitors (e.g. Cyclosporine/ Tacrolimus) (AND)
• Any of the following: Azathioprine/ Mycophenolate mofetil (MMF)/ mTOR kinase inhibitors (e.g. Sirolimus)
MOST common combination = Prednisolone + Tacrolimus + MMF
Causes of early renal allograft dysfunctions
- Urological complication (e.g. leakage)
- Vascular complication (e.g. renal vein thrombosis)
- Infection (e.g. UTI, viral infection)
- Drug toxicity (e.g. rejection prophylaxis drugs)
Long-term complications of renal transplant
Opportunistic infections: CMV, Pneumocystis pneumonia, BK virus, TB
Malignancy: e.g. Post-transplant lymphoproliferative disorders
Cardiovascular disease *most deadly
Drug-related S/E
Chronic allograft injury *most common cause of late graft fallure
Recurrence of primary disease: e.g. IgA nephropathy, membranous nephropathy, FSGS
Definition of Chronic allograft injury in renal transplant
Slow, progressive decline in renal graft function, proteinuria, hypertension
With histological features of interstitial fibrosis, tubular atrophy
Pneumocystis pneumonia
- S/S
- Prophylaxis treatment
Acute onset of fever, cough and SoB with type I respiratory failure
High-dose Septrin prophylaxis
Cyclosporine
Class
MoA
S/E
Class: Calcinuerin inhibitor
MoA:
Bind to cytoplasmic receptor protein called cyclophilin (CpN)
Inhibits calcineurin phosphatase
Prevent activation of nuclear factor (NFATc)
Inhibits synthesis of IL-2
↓ Cell-mediated immunity
S/E:
Nephrotoxicity
Gum hyperplasia
Hyperkalemia
Hypertension
Hyperlipidemia
Tacrolimus
Class
Drug interactions
MoA
S/E
Calcineurin inhibitor
D/D: Cyclosporine, additive nephrotoxicity
MoA:
Binds to FK-binding protein
Inhibits calcineurin phosphatase
Prevent activation of nuclear factor (NFATc)
Inhibits synthesis of IL-2
↓ Cell-mediated immunity
S/E:
Nephrotoxicity
Neurotoxicity
Hyperkalemia
Hypertension
Hyperlipidemia
DM
Sirolimus
Drug interaction
MoA
S/E
D/D: Aggravates cyclosporine-induced renal dysfunction
MoA:
Binds to FK-binding protein
Interfere with mTOR signal
Block T-cell proliferation in response to IL-2 stimulus
S/E:
Pancytopenia
Hypertension
Hyperlipidemia
Azathioprine
Class
MoA
S/E
Anti-metabolite (Folate antagonist)
MoA:
Azathioprine is converted into 6-MP
6-MP is converted into thioinosine monophosphate (TIMP)
TIMP inhibits de novo purine ring synthesis which is required for lymphocyte proliferation
TIMP is converted into 6-thioguanine (6-TG)
6-thioguanine (6-TG) is incorporated in DNA as a false nucleotide
S/E:
Hepatotoxicity
Bone marrow toxicity
(Myelosuppression)
• Anemia
• Leukopenia
• Thrombocytopenia
Pancreatitis
Mycophenolate mofetil
MoA
S/E
MoA:
Inhibits inosine monophosphate dehydrogenase
Block purine synthesis (guanosine phosphate) which is required for lymphocyte proliferation
Deprive B and T cells of a key component of nucleic acids
S/E:
GI disturbances:
Abdominal pain
Diarrhea
Constipation
Nausea and vomiting
Myelosuppression:
Anemia
Leukopenia
IL-2 antagonists
Examples
MoA
S/E
Basiliximab
Daclizumab
MoA:
Anti-CD25 antibodies block IL-2 receptor on activated T-cells
Inhibits IL-2 mediated T-cell activation and proliferation
S/E:
None
Prednisolone for organ transplant
MoA
S/E
MoA:
Inhibition of nuclear factor kappa B activation (NFκB)
Binding to glucocorticoid response elements in cytokine genes
Inhibits cytokine production by T cells and macrophages
Disrupt T-cell activation and macrophage-mediated tissue injury
S/E:
Cushingoid changes
Cataracts
Peptic ulcer disease (PID)
Proximal myopathy
Thinning of skin
Osteoporosis/ AVN
Hypertension
Hyperlipidemia
Glucose intolerance
Immunosuppression
