Renal replacement therapy

Renal replacement therapy (RRT) is used to support or replace kidney function (i.e., remove toxins, metabolites, and/or water from the body). RRT is indicated in various acute (e.g., acute renal injury, poisoning, refractory fluid overload) and chronic conditions (e.g., chronic kidney disease). There are three main RRT modalities: dialysis (either hemodialysis or peritoneal dialysis), hemofiltration, and kidney transplantation. The choice of RRT depends on the anticipated duration of treatment (acute RRT vs. chronic RRT), indications for treatment, patient characteristics, and patient preference. Dialysis uses diffusion to remove solutes from the blood across a semipermeable membrane, while hemofiltration uses convection; both modalities employ varying degrees of ultrafiltration to remove water. Kidney transplantation is the most comprehensive method of RRT in patients with end-stage renal disease (ESRD) and is covered separately in “Transplantation.”

• Acute renal replacement therapy
  • Performed in patients with acute conditions (patients may have no preexisting renal disease): e.g., acute kidney injury (AKI), poisoning, acute decompensated heart failure
  • Modalities include hemodialysis and hemofiltration
• Chronic renal replacement therapy
  • Performed in patients with ESRD
  • Modalities include peritoneal dialysis, hemodialysis, hemofiltration, and kidney transplantation

Approach ^[1]

The following is applicable for all patients in whom acute or chronic RRT is being considered.

• Consult nephrology early; optimizing medical management may prevent the need for RRT.
• Stabilize the patient.
  • Manage any life-threatening and/or urgent conditions, e.g.:
    • Initiate management of hyperkalemia.
    • Address acid-base disorders.
    • Provide immediate hemodynamic support for undifferentiated shock.
  • Treat any poisoning or overdose (e.g., salicylate toxicity).
  • Consider diuresis and use fluids judiciously in patients with clinical signs of volume overload.
• Perform a thorough clinical evaluation, paying particular attention to the following:
  • Symptoms of uremia
  • Relevant diagnoses (e.g., sepsis, hypotension, prior and/or existing kidney disease)
  • Laboratory studies
    • CBC: for anemia of chronic kidney disease (CKD)
    • CMP: for renal function and electrolyte abnormalities
    • Blood gas: for acid-base status
    • Urine studies: to assess for proteinuria, hematuria, and infection
• Discontinue and avoid nephrotoxic medications.
• Determine indication(s) for dialysis.
• In consultation with nephrology and/or ICU, determine the preferred RRT modality and obtain appropriate access.

RRT should be initiated before potentially life-threatening complications of renal failure develop. ^[2]

Indications for RRT ^[3][4][5]

• Severe metabolic acidosis, e.g., pH < 7.1 and/or serum bicarbonate < 12 mmol/L ^[6][7]
• Refractory severe electrolyte abnormalities, e.g., hyperkalemic emergency, hypercalcemic crisis ^[6][7]
• Symptoms of uremia, particularly uremic pericarditis, uremic encephalopathy, and/or bleeding
• Fluid overload refractory to medical management, e.g., in CKD, CHF
• Poisoning or overdose with a dialyzable substance, e.g., lithium, toxic alcohols
• Additionally, in ESRD: ^[4][5]
  • Refractory hypertension
  • Anorexia or weight loss despite nutritional interventions

Indications for urgent RRT: “A.E.I.O.U.” -Acidosis, Electrolyte abnormalities (hyperkalemia), Ingestion (of poisons), Overload (fluid), Uremic symptoms

Dialyzable medications and poisons: “I STUMBLED” - Isoniazid, isopropyl alcohol; Salicylates; Theophylline, Tenormin^® (atenolol); Urea; Methanol; Barbiturates; Lithium; Ethylene glycol; Dabigatran, Depakote^®(valproic acid)

RRT mechanisms and modalities ^[2][7][8]

Select the RRT modality based on therapeutic goals, availability, and local expertise. Kidney transplantation is covered separately in “Transplantation.”

Mechanisms

• Diffusion
  • Solutes move across a semipermeable membrane down their concentration gradient.
  • Smaller molecules have faster rates of diffusion and are cleared more easily.
• Convection
  • Hydrostatic pressure gradients drive water (i.e., ultrafiltration) and solutes across a semipermeable membrane.
  • Solutes of all sizes can be effectively cleared; the solutes cleared depends on the pore size in the filter membrane.

Modalities

• Peritoneal dialysis
• Hemodialysis or hemofiltration

Basic principles ^[2][9][10]

• Hemodialysis: utilizes diffusion and a small degree of ultrafiltration to remove solutes and water from the blood
  • More effective at removing small molecules (e.g., urea, creatinine, ammonia) than larger molecules
  • Blood is pumped through the dialysis unit on one side of a semipermeable membrane and dialysate in the opposite direction on the other side of the membrane.
  • Molecules diffuse across the semipermeable membrane down their concentration gradient.
• Hemofiltration: utilizes convection and a high degree of ultrafiltration to remove solutes and water from the blood
  • More effective at removing medium to large molecules (e.g., cytokines, myoglobin) than hemodialysis ^[10]
  • Blood is pumped through a machine and the difference in hydrostatic pressures drives water and solutes across a semipermeable membrane.
  • Lost plasma volume is replaced with a physiologic crystalloid solution. ^[2]
• Hemodiafiltration
  • Combination of hemodialysis and hemofiltration
  • Removes molecules of all sizes (most effective method for medium-sized molecule clearance)
• Administration options
  • Intermittent renal replacement therapy
    • Typically occurs over 3–5 hours; may last 6–18 hours (prolonged intermittent renal replacement therapy) ^[2][7]
    • Most common option for outpatient administration in patients with CKD; also used for acute RRT ^[7]
  • Continuous renal replacement therapy ^[7]
    • Gradual fluid and solute clearance over 24 hours
    • Used almost exclusively for acute RRT
    • Preferred if fluid shifts are contraindicated ^[3]

Intermittent RRT can be performed in a clinic or at home by the patient after adequate training.

Access ^[1][3][11]

Consider the anticipated duration of RRT and patient factors (e.g., preference, life expectancy, mobility) to determine the most appropriate type of access for RRT.

Venous catheter for renal replacement therapy

• Indications ^[1][11]
  • Urgent and/or short-term RRT
  • If an AV fistula or AV graft cannot be used
  • Limited life expectancy
• Types of catheter ^[1][3]
  • Nontunneled hemodialysis catheter
    • Typically used as initial access in urgent acute RRT
    • High infection risk; use limited to a maximum of 2 weeks ^[11]
  • Tunneled hemodialysis catheter
    • Lower infection risk and more stable than nontunneled catheters
    • Suitable for long-term use
• Placement: central venous access, preferably in the right internal jugular vein ^[1][3][11]
• Structure ^[9]
  • Large bore, double-lumen
  • Blood is removed from the vein through one lumen and returned through the other lumen.

Arteriovenous access ^[11]

• Indication: for maintenance dialysis in ESRD
• Procedure
  • An anastomosis is created between an artery and a vein to provide long-term large-bore vascular access
  • Usually created in the nondominant arm (less impairment) between the radial artery and the cephalic vein (i.e., radiocephalic fistula)
• Types of AV access
  • Arteriovenous fistula: an artery is directly connected to a vein
  • Arteriovenous graft: a synthetic or biological conduit is used to connect an artery to a vein

AV fistulas need approximately 4–6 weeks to mature (i.e., enlargement and thickening of the vein in response to arterial pressure); maturation is unsuccessful in up to 60% of patients. Arrange AV access before dialysis is likely to be required. ^[11]

Complications of hemodialysis ^[2][7][11]

Vascular access complications ^[11]

• Loss of access due to thrombosis or stenosis
• Infections e.g., skin and soft tissue infection, central line-associated bloodstream infection
• Local aneurysm
• AV access steal syndrome: painful ischemia of the hand secondary to the AV fistula or graft shunting blood away from the distal limb
• Dialysis vascular access hemorrhage ^[12][13][14]
  • Apply firm pressure for 15–20 minutes; avoid occluding the vessel.
  • If the patient is hemodynamically unstable:
    • Manage as hemorrhagic shock
    • Place tourniquets above and below the site and attempt a figure of 8 or purse-string suture.
    • Determine time of last dialysis and consider anticoagulant reversal.
  • Urgently consult vascular surgery if bleeding is heavy, persists, or recurs.

Cardiovascular complications ^[2]

• Hypotension ^[9]
• Heart failure ^[15]

Increased bleeding risk ^[16]

• Caused by platelet dysfunction due to CKD and/or platelet contact with the dialysis membrane ^[16]
• Avoid systemic anticoagulation solely to maintain or improve hemodialysis catheter patency. ^[11]

Dialysis disequilibrium syndrome ^[3][17]

• Definition: the development of acute cerebral edema secondary to the rapid extraction of osmotically active substances (e.g., urea, NaCl) from the blood
• Risk factors ^[18]
  • First dialysis sessions
  • Extremely elevated BUN
  • Metabolic acidosis
  • Preexisting neurological abnormalities
  • Hyperglycemia or hypernatremia
• Prevention ^[17]
  • Use hemofiltration over hemodialysis in patients with risk factors.
  • If hemodialysis is performed, provide regular, slow dialysis.
  • Consider adjusting the dialysate to mitigate osmotic shifts. ^[17][18]
• Management: Monitor patients for symptoms of cerebral edema and initiate management of raised ICP if present. ^[17]

Other complications ^[2][7]

• Acquired cystic kidney disease ^[19]
• Cramps
• Electrolyte abnormalities, e.g., hypophosphatemia
• Dialysis-related amyloidosis, which can cause carpal tunnel syndrome ^[20][21]
• Allergic reaction to the equipment or dialysate ^[3]

Cardiovascular disease is the leading cause of death in patients on dialysis and kidney transplant recipients. ^[5]

Basic principles ^[2][22]

• Mechanism: utilizes diffusion across the peritoneum (acts as a semipermeable membrane) and ultrafiltration to remove water and solutes from the blood
• Procedure
  • Dialysate is instilled into the abdomen and left for a set period of time (i.e., dwell time) to allow diffusion.
  • Hypertonic dialysate draws water across the peritoneal membrane via osmosis.
  • The effluent is removed at the end of the dwell time.
• Administration options: self-administered by highly adherent patients (or their carers) at home ^[23]
  • Continuous ambulatory peritoneal dialysis
    • Performed manually 3–5 times/day
    • No requirement to be connected to a machine
  • Automated peritoneal dialysis
    • Automated exchange cycles, typically scheduled overnight
    • Patients are connected to a machine.
• Peritoneal catheter
  • Location: placed into the peritoneal cavity and tunneled to an exit site ^[22]
  • Placement: laparoscopic, percutaneous (with or without image guidance), or open surgical approach

Because of the high risk of complications, individuals must be trained and able to demonstrate strict adherence to correct techniques before being allowed to perform home peritoneal dialysis. ^[2]

Complications of peritoneal dialysis ^[2][22][24]

• Metabolic disturbances: weight gain, hyperglycemia
• Infections
  • Exit site and catheter tunnel infections
  • Peritoneal dialysis-associated peritonitis
• Protein loss: hypoalbuminemia ^[25]
• Abdominal hernias: umbilical and inguinal hernias are most common ^[26]
• Leakage of dialysate
• Pleural effusion (rare) ^[27][28]

Frequently examine the peritoneal dialysis catheter and exit site for signs of infection (e.g., swelling, purulent drainage); consider ultrasound for a more detailed assessment if infection is suspected. ^[24]

Risk factors ^[29]

• Obesity
• Smoking
• Depression
• Hypoalbuminemia
• Staphylococcus aureus nasal carriage
• Previous exit site infection
• Inadequate peritoneal dialysis training
• Pets in the area where peritoneal dialysis is being performed
• Invasive abdominal procedures (e.g., colonoscopy, cholecystectomy, hysteroscopy)

Clinical features ^[29]

• Often asymptomatic and identified by cloudy peritoneal effluent
• Clinical features of peritonitis may be present.

Diagnostics ^[29]

• Perform a comprehensive clinical evaluation, including an examination of the catheter.
• Obtain a peritoneal fluid sample.
  • Send for cell count with differential, Gram stain, and cultures.
  • If the effluent is cloudy, initiate empiric antibiotic therapy.
• Systemic signs of infection: Initiate diagnostic workup for sepsis.
• Confirm peritonitis if ≥ 2 of the following are present:
  • Clinical features of peritonitis
  • Peritoneal fluid with > 100 WBCs/mcL (typically > 50% polymorphonuclear cells) ^[30]
  • Positive peritoneal fluid culture

Initiate empiric antibiotic therapy for presumed peritonitis in all patients with cloudy peritoneal effluent, even if they are asymptomatic. ^[29]

Management ^[29][31][32]

Initial management

• Features of sepsis
  • Admit the patient.
  • Initiate sepsis management, including empiric systemic antibiotics. ^[29]
• No systemic signs of infection (common)
  • Consult nephrology and infectious diseases; most cases can be managed in an outpatient setting
  • Initiate broad-spectrum empiric intraperitoneal antibiotics. ^[29]
• Empiric antibiotic regimens
  • Adjust the dose based on renal function per hospital protocol.
  • Recommended regimens include: ^[29][32]
    • Vancomycin OR first-generation cephalosporin (gram-positive cover)
    • PLUS third-generation cephalosporin OR aminoglycoside (gram-negative cover)

Ongoing management

• Adjust antibiotics based on culture and susceptibility results.
• Start antifungal prophylaxis (oral nystatin or fluconazole). ^[29]
• Provide supportive treatment as needed (e.g., pain management, antiemetics).
• Patients with relapsing or refractory peritonitis or confirmed fungal peritonitis: Consider removal of the peritoneal dialysis catheter and temporary hemodialysis. ^[32]

Prevention ^[29]

• Antibiotic prophylaxis
  • Perioperative antibiotic prophylaxis prior to insertion of the peritoneal dialysis catheter
  • Systemic prophylaxis prior to certain procedures (e.g., dental procedures, invasive abdominal procedures)
  • Daily application of topical antibiotics to the catheter exit site.
• Patient education on peritoneal dialysis catheter care
  • Keeping the exit site clean ^[24]
  • Practicing thorough hand hygiene prior to dialysis exchange
• Prompt treatment of exit site infections
• Addressing modifiable risk factors

Educate patients to monitor effluent characteristics at home and seek medical attention if they observe any changes suggestive of peritonitis (e.g., cloudiness).

• Monitor for complications (see “Complications” in “Hemodialysis and hemofiltration” and “Peritoneal dialysis”).
• Avoid nephrotoxic medications and adjust medications accordingly. ^[7][33]
• Involve a renal dietitian in management.
• Monitor fluid balance closely.
• Coordinate necessary vaccinations with the treating nephrologist. ^[34][35][36]
  • Likely to be vaccine nonresponders; additional and/or higher doses and serological testing may be needed
  • Avoid live vaccines in immunosuppressed posttransplant patients.
• Preserve active and future vascular access sites. ^[11]
  • Do not use blood pressure cuffs on extremities with active RRT access.
  • Avoid forearm venipunctures.
  • Coordinate any nonemergent line placement with nephrology.
• Avoid unnecessary blood transfusions in patients awaiting kidney transplantation. ^[34][37]
• Discuss advance care planning with patients on dialysis. ^[38]

Contact nephrology and/or a pharmacist for all medication dosing and if clinical management may affect or be affected by RRT.

Do not access any RRT lines except in an emergency, if no other access is available.