Renal Replacement Therapy

Renal replacement therapy replaces excretory and homeostatic kidney functions through extracorporeal blood purification, the peritoneal membrane, or a transplanted kidney. This article addresses dialysis modalities.

Principles of solute and fluid removal

• Diffusion: solute movement down a concentration gradient across a semipermeable membrane, efficient for small molecules such as urea, potassium and creatinine.
• Convection (ultrafiltration with replacement fluid): solute drag with plasma water, better for middle molecules.
• Ultrafiltration: fluid removal driven by transmembrane pressure.
• Adsorption: binding of molecules to the membrane.

Modalities

• Intermittent haemodialysis: 3 to 5 hours, three times weekly in end-stage kidney disease, or daily in acute settings.
• Prolonged intermittent therapy (SLED): 6 to 12 hours at lower blood flow (150 to 200 mL/min) and dialysate flow, used in haemodynamic instability.
• Continuous renal replacement therapy: CVVH (convection), CVVHD (diffusion) and CVVHDF (both), for critically ill patients with haemodynamic instability or raised intracranial pressure.
• Peritoneal dialysis: continuous ambulatory (CAPD, usually four exchanges daily) or automated (APD, overnight cycler).
• Haemoperfusion and plasma exchange: specialised adsorptive and plasma removal therapies.

Indications in acute kidney injury (any one of the following)

• Refractory hyperkalaemia (potassium above 6.5 mmol/L, or ECG changes) despite medical therapy.
• Severe metabolic acidosis (pH below 7.1 or bicarbonate below 12 mmol/L) not responding to treatment.
• Fluid overload with pulmonary oedema unresponsive to diuretics.
• Uraemic complications: pericarditis, encephalopathy, uraemic bleeding, intractable nausea.
• Dialysable intoxications: lithium, methanol, ethylene glycol, salicylate, metformin-associated lactic acidosis, valproate, theophylline, and some others.

Early (accelerated) initiation in AKI without these indications does not improve survival and increases catheter complications, so a watchful waiting approach is preferred unless oliguria persists beyond 72 hours with worsening trends.

Indications in chronic kidney disease

• Start dialysis when symptoms or signs of uraemia appear (nausea, anorexia, pruritus, pericarditis, encephalopathy, weight loss), or fluid, potassium, acid-base or blood pressure control fails, typically at eGFR 5 to 10 mL/min/1.73 m2. Routine initiation based on eGFR alone, at eGFR 10 to 14, shows no benefit over symptom-guided initiation.

Prognosis: five-year survival on dialysis is about 40 to 50%, with cardiovascular disease the leading cause of death. Survival is better with transplantation, home therapies in selected patients, and early fistula use.

Preparation and assessment

• Patients approaching dialysis show fluid retention, hypertension, anaemia, hyperphosphataemia, secondary hyperparathyroidism, acidosis and uraemic symptoms.
• Review comorbidity, frailty, life expectancy, patient goals and access options. Conservative kidney management is appropriate for patients with advanced age or frailty, where dialysis may not improve survival or quality of life.

Complications of haemodialysis

• Intradialytic hypotension (10 to 30% of sessions): dizziness, cramps, nausea, caused by excessive ultrafiltration, autonomic neuropathy, antihypertensives or cardiac dysfunction.
• Muscle cramps, headache, chest pain, itching.
• Dialysis disequilibrium syndrome: headache, nausea, confusion, seizures or coma, from cerebral oedema after rapid urea removal in the first sessions of severely uraemic patients.
• Air embolism: sudden dyspnoea, chest pain, cough, neurological symptoms.
• First use syndrome and anaphylactoid reactions: with ethylene oxide sterilised dialysers or ACE inhibitors with AN69 membranes.
• Catheter-related bloodstream infection: fever and rigors during dialysis, exit-site erythema or pus. Staphylococcus aureus is the commonest organism.
• Access problems: thrombosis, stenosis (falling flows, prolonged bleeding after needle removal, arm swelling), aneurysm, infection, steal syndrome, and heart failure from high-output fistula.
• Bleeding: from heparin or uraemic platelet dysfunction.
• Hyperkalaemia or hypokalaemia after dialysis, hypophosphataemia in prolonged therapy, and hypocalcaemia with citrate.

Complications of peritoneal dialysis

• Peritonitis: cloudy effluent, abdominal pain, fever. A dialysate white cell count above 100/µL with over 50% neutrophils after a dwell of at least 2 hours is diagnostic.
• Exit-site and tunnel infection, catheter malfunction (constipation, migration, omental wrapping, fibrin), hernia, leaks, hydrothorax, encapsulating peritoneal sclerosis, hyperglycaemia, weight gain, and loss of ultrafiltration.

Complications of continuous therapy: hypothermia, hypophosphataemia, hypokalaemia, hypomagnesaemia, citrate accumulation (rising total to ionised calcium ratio above 2.5), filter clotting, antibiotic underdosing, and bleeding.

Pre-dialysis assessment

• Creatinine, urea, eGFR, electrolytes, bicarbonate, calcium, phosphate, PTH, haemoglobin, ferritin and transferrin saturation, albumin, glucose and HbA1c.
• Hepatitis B surface antigen and antibody, hepatitis C and HIV serology before starting in-centre therapy, with vaccination for non-immune patients.
• ECG, echocardiography (volume status and ventricular function), chest radiograph and renal ultrasound.
• Vascular mapping with duplex ultrasound of arm arteries and veins (artery diameter 2 mm or more, vein diameter 2.5 mm or more) before fistula creation. Preserve veins by avoiding venepuncture and peripherally inserted central catheters in the non-dominant arm.

Adequacy monitoring

• Haemodialysis: single-pool Kt/V target at least 1.2 per session (aim 1.4) for thrice weekly therapy, or urea reduction ratio above 65%. Monthly bloods for urea, electrolytes, calcium, phosphate, albumin and haemoglobin, with PTH every 3 months.
• Peritoneal dialysis: weekly Kt/V 1.7 or more including residual renal function, with ultrafiltration and peritoneal equilibration testing.
• Continuous therapy: delivered effluent dose 20 to 25 mL/kg/h (prescribe 25 to 30 mL/kg/h to compensate for downtime).
• Dry weight is reassessed clinically with blood pressure, oedema, bioimpedance or lung ultrasound.

Access surveillance: clinical monitoring (thrill, bruit, arm swelling, prolonged bleeding), measured access flow below 600 mL/min (or a fall over 25%) in grafts and fistulas, duplex ultrasound and fistulography for dysfunction.

Infection diagnosis: blood cultures from both the catheter and a peripheral vein, exit-site swab, and dialysate cell count and culture inoculated into blood culture bottles for peritonitis.

Vascular access

• Preferred: arteriovenous fistula (radiocephalic, then brachiocephalic or brachiobasilic transposition) created 2 to 3 months before expected dialysis start, followed by arteriovenous graft, then tunnelled cuffed catheter. Avoid subclavian vein catheters.
• Non-tunnelled catheters (right internal jugular preferred, ultrasound-guided; femoral for short-term use) for acute need. Tunnelled cuffed right internal jugular catheters for expected use beyond 3 weeks.
• Catheter lock solutions between sessions: heparin 1000 to 5000 units/mL, or 4% sodium citrate. Alteplase 2 mg in 2 mL per lumen for 30 to 60 minutes clears dysfunctional catheters. Taurolidine-containing locks and antibiotic locks reduce infection.
• Treat fistula stenosis with angioplasty. Surgical revision for failing access.

Haemodialysis prescription

• Typical: 4 hours, three times weekly, blood flow 300 to 400 mL/min, dialysate flow 500 mL/min, high-flux dialyser. Hemodiafiltration improves survival in some trials.
• Dialysate: sodium 138 to 140 mmol/L, potassium 2 to 3 mmol/L (individualised, avoid 1 mmol/L), bicarbonate 32 to 35 mmol/L, calcium 1.25 to 1.5 mmol/L, temperature 35.5 to 36.5 degrees C (cooler dialysate reduces intradialytic hypotension).
• Ultrafiltration rate below 13 mL/kg/h, and interdialytic weight gain below 4% of dry weight. Fluid restriction about 500 mL plus the previous day's urine output, sodium restriction under 2 g/day.
• First session in severe uraemia: short (2 hours), low blood flow (150 to 200 mL/min), aim for urea reduction under 30 to 40%, to prevent disequilibrium syndrome. Mannitol 12.5 to 25 g IV or hypertonic sodium dialysate can help prevention.
• Anticoagulation: unfractionated heparin bolus 2000 to 5000 units then 500 to 1500 units/h, or enoxaparin 0.5 to 1 mg/kg pre-dialysis. For bleeding risk, use saline flushes, regional citrate or heparin-free dialysis.

Continuous renal replacement therapy

• Regional citrate anticoagulation (4% trisodium citrate prefilter with calcium chloride or gluconate infusion postfilter, monitoring ionised calcium) is preferred over heparin in most ICU patients, and prolongs filter life. Avoid in severe liver failure and shock with high lactate.
• Dose delivered 20 to 25 mL/kg/h effluent. Adjust drug doses, especially antibiotics (for example piperacillin-tazobactam 4.5 g every 8 hours, meropenem 1 g every 8 hours during CVVHDF).
• Start with a blood flow of 150 to 250 mL/min, and use warm replacement fluid to prevent hypothermia. Phosphate supplementation to avoid hypophosphataemia.

Peritoneal dialysis

• Exchanges: 2 L (1.5 to 2.5 L) dwell volumes, three to five exchanges daily. Dextrose 1.5%, 2.3% and 4.25% solutions, with icodextrin 7.5% for the long dwell in ultrafiltration failure. Low glucose degradation product solutions preserve the membrane.
• Peritonitis treatment: send effluent for culture, give intraperitoneal antibiotics empirically without delay: vancomycin 15 to 30 mg/kg every 5 days (or cefazolin 15 mg/kg daily) plus ceftazidime 1 to 1.5 g daily (or an aminoglycoside). Tailor to culture. Duration 14 days (21 days for S. aureus, enterococci, Pseudomonas or Gram-negatives). Antifungal prophylaxis (fluconazole 200 mg alternate days) with antibiotic courses. Remove catheter for fungal peritonitis, refractory peritonitis (no improvement at 5 days) or relapsing peritonitis.
• Exit-site infection: topical mupirocin or gentamicin cream, oral cefalexin 500 mg twice daily or flucloxacillin.

Catheter-related bloodstream infection (haemodialysis)

• Empirical vancomycin (20 mg/kg load, then 500 mg to 1 g post dialysis based on pre-dialysis levels, target 15 to 20 mg/L) plus gentamicin 1 mg/kg after dialysis or ceftazidime 1 to 2 g after dialysis. Narrow by culture. Treat for 2 to 3 weeks with antibiotic lock therapy, and for 4 to 6 weeks if complicated (endocarditis, osteomyelitis). Remove the catheter in tunnel infection, sepsis or persistent bacteraemia at 72 hours.

Dialysis-associated conditions

• Anaemia: epoetin alfa 50 to 100 units/kg three times weekly (or darbepoetin 0.45 micrograms/kg weekly) targeting haemoglobin 10 to 11.5 g/dL. IV iron sucrose 100 mg with dialysis sessions to maintain ferritin 200 to 500 µg/L and transferrin saturation 20 to 30%. Roxadustat 70 mg three times weekly is an oral alternative.
• Mineral bone disease: phosphate 0.8 to 1.5 mmol/L, binders with meals (sevelamer 800 to 1600 mg three times daily, calcium carbonate 500 mg to 1 g with meals, lanthanum 500 to 1000 mg with meals), dietary phosphate restriction, cinacalcet 30 to 180 mg daily, etelcalcetide 5 mg IV after dialysis, and active vitamin D (calcitriol 0.25 to 1 microgram) for hyperparathyroidism.
• Hyperkalaemia: dietary restriction, patiromer 8.4 g daily or sodium zirconium cyclosilicate 5 to 10 g daily, and avoid trigger drugs.
• Hypertension: dry weight reduction, then beta blockers or ACE inhibitors or ARBs.
• Intradialytic hypotension: reduce ultrafiltration rate, cool dialysate, hold antihypertensives before dialysis, midodrine 5 to 10 mg 30 minutes before dialysis, extended session times.
• Nutrition: protein 1.0 to 1.2 g/kg/day, potassium 2 to 3 g/day, adequate calories 30 to 35 kcal/kg/day. Water-soluble vitamin supplementation.
• Vaccination: hepatitis B (double dose 40 micrograms at 0, 1, 2 and 6 months, titre check), pneumococcal, influenza annually, COVID-19.
• Cardiovascular risk: statin if age 50 or over (atorvastatin 20 mg), aspirin for secondary prevention.
• Medication dosing adjusted to residual function and dialysis clearance.

Withdrawal and conservative care

• Shared decision making with a time-limited trial. Withdraw in patients with irreversible decline and poor quality of life, with palliative care input (symptom control with haloperidol 0.5 to 1 mg for nausea, opioids such as hydromorphone or fentanyl in renal failure, avoid morphine).