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Renal Replacement Therapy

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Renal replacement therapy (RRT) refers to a group of medical treatments used to replace the essential functions of the kidneys in patients with acute or chronic kidney failure.

  • renal replacement therapy
  • hemodialysis
  • peritoneal dialysis
  • kidney failure
  • renal care

By Dr. Ayesha Fatima

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  1. Slide 1. RENAL REPLACEMENT THERAPY Prepare By Dr Ayesha Fatima Pharm D Assistant Professor Dept of Pharmacy Practice
  2. Slide 2.  Renal replacement therapy (RRT) refers to medical treatments that replace the normal functions of the kidneys in patients with acute or chronic kidney failure.  It helps in: 1. Removal of waste products (urea, creatinine) 2. Regulation of electrolytes 3. Removal of excess fluid 4. Maintenance of acid–base balance
  3. Slide 3. General Indications Classical Indications 1. Acute Kidney Injury (AKI) 2. Chronic Kidney Disease (CKD stage 4–5) 3. End-Stage Renal Disease (ESRD / CKD stage 5) 1. Fluid overload – Pulmonary edema, Diuretic resistance 2. Electrolyte imbalance – Severe hyperkalemia 3. Metabolic acidosis – Refractory acidosis 4. Uremic complications – Pericarditis, Encephalopathy 5. Bleeding tendencies (uremic platelet dysfunction) 6. Dialyzable intoxications – Lithium, Salicylates, Toxic alcohols 7. Rapid fall in GFR 8. Risk of solute imbalance or toxicity
  4. Slide 4. Types (Forms) of Renal Replacement Therapy 1. Primary modalities 1. Hemodialysis (HD) 2. Peritoneal Dialysis (PD) 3. Kidney Transplantation 2. Other extracorporeal techniques 1. Hemofiltration 2. Hemodiafiltration
  5. Slide 6. Basic Principle of RRT All RRT modalities work on a common principle: Blood is exposed to a dialysate across a semipermeable membrane This allows removal of: Low molecular weight solutes, Excess fluids and Electrolytes Molecular Clearance Concept: Low molecular weight solutes (generally < 50,000 Daltons) pass easily, Larger molecules require convection - based techniques Mechanisms of Solute and Fluid Removal 1. Diffusion: Passive movement of solutes from high → low concentration. a. Diffusion in renal replacement therapy is the passive movement of solutes across a semipermeable membrane from the blood compartment to the dialysate compartment (or vice versa) down a concentration gradient. b. Occurs between blood and dialysate c. Driven by concentration difference d. Most effective for small molecular weight solutes (e.g., urea, creatinine, potassium) e. Primary mechanism in hemodialysis f. Depends on: Concentration gradient and Molecular size
  6. Slide 7. 2. Ultrafiltration: Movement of fluid due to a pressure gradient Fluid moves from high pressure → low pressure 1. Ultrafiltration in renal replacement therapy is the movement of water across a semipermeable membrane from the blood to the dialysate side due to a transmembrane pressure gradient. 2. Driven by hydrostatic pressure difference or osmotic pressure 3. Responsible for removal of excess body fluid 4. Occurs in: Hemodialysis, Hemofiltration, Peritoneal dialysis 3. Convection: Solutes are carried along with fluid movement (solvent drag) 1. Convection in renal replacement therapy is the transport of solutes across a semipermeable membrane along with the movement of water during ultrafiltration (solvent drag). 2. Solutes are carried with bulk flow of fluid 3. Effective for middle and larger molecular weight solutes 4. Primary mechanism in hemofiltration and hemodiafiltration
  7. Slide 8. Hemodialysis (HD)  Hemodialysis is a renal replacement therapy in which blood is circulated outside the body and purified through a dialyzer (artificial kidney), where waste products, excess fluids, and electrolytes are removed across a semipermeable membrane.  Principle of Hemodialysis 1. Diffusion 2. Ultrafiltration 3. Convection  Blood and dialysate flow on opposite sides of a semipermeable membrane.
  8. Slide 10. Mechanisms involved  Diffusion : Movement of solutes from high → low concentration 1. Depends on: Concentration gradient, Molecular size, Charge of molecules, Membrane characteristics, Blood and dialysate flow rate 2. More effective for small molecules (urea, creatinine)  Ultrafiltration: Movement of water due to pressure gradient (hydrostatic/osmotic) 1. Responsible for removal of excess fluid  Convection: Solutes move along with water (solvent drag) 1. Effective for larger molecules  Diffusion and convection can be independently controlled and individualized
  9. Slide 11. Vascular Access for Hemodialysis  Access is required to remove and return blood:  Common sites: Internal jugular vein, Femoral vein, Subclavian vein  Types: Double-lumen catheter: One lumen: arterial (blood removal), Other lumen: venous (blood return)  Long-term access (important addition): Arteriovenous (AV) fistula (preferred), AV graft Procedure of Hemodialysis 1. Blood is withdrawn from the patient through vascular access 2. Heparin is added to prevent clotting, Reduced or avoided in patients with high bleeding risk 3. Blood is pumped into the dialyzer (artificial kidney) 4. Inside the dialyzer: Blood flows through hollow fibers or flat plates 5. Dialysate flows in the opposite direction (countercurrent flow) to maximize diffusion 6. Waste products and excess fluid move into dialysate 7. Purified blood is returned to the patient
  10. Slide 12.  Dialyzer Structure: Contains a semipermeable membrane Types: Hollow fiber dialyzer (most common), Flat plate dialyzer  Composition of Dialysate: Dialysate is a solution resembling extracellular fluid, containing: 1. Water + electrolytes: 2. Sodium 3. Potassium 4. Calcium 5. Magnesium  Composition can be modified: 1. Adjust potassium for hyperkalemia 2. Increase bicarbonate for acidosis 3. Adjust calcium levels as needed  Control of Fluid Removal 1. Achieved by manipulating: 2. Hydrostatic pressure gradient 3. Dialysate and blood circuit pressures 4. Determines rate of ultrafiltration
  11. Slide 13. Feature Intermittent Hemodialysis (IHD) Continuous Hemodialysis (CRRT) Definition Hemodialysis performed at intervals (sessions) Hemodialysis performed continuously over 24 hours Frequency 3–4 times per week Continuous (24 hours/day) Duration Short sessions (3–5 hours) Prolonged therapy (24 hours or longer) Solute Clearance Rapid and efficient Slow and gradual Fluid Removal Rapid fluid removal Gradual fluid removal Hemodynamic Stability Less stable (risk of hypotension) Better stability (preferred in unstable patients) Indications Stable patients with ESRD Critically ill patients (ICU, AKI) Electrolyte Control Rapid correction Controlled, gradual correction Setting Usually dialysis center ICU setting Advantages Faster toxin removal, shorter duration Better tolerated, precise fluid and electrolyte control Disadvantages Rapid shifts → hypotension, not suitable for unstable patients Requires continuous monitoring, more complex and costly
  12. Slide 14. Complications Advantages of Hemodialysis Disadvantages of Hemodialysis 1. Hypotension (most common), Hypertension 2. Muscle cramps 3. Nausea, Vomiting 4. Headache 5. Chest pain, Back pain, Fever and chills (infection) 6. Infection, Thrombosis High solute clearance efficiency Requires frequent hospital visits (2–3 times/week) Rapid correction of electrolyte imbalance Loss of patient independence Rapid removal of fluid overload Risk of infections (vascular access related) Well monitored in center- based dialysis Risk of thrombosis (vascular access) Effective for acute conditions Hemodynamic instability (e.g., hypotension) Long-term decline in residual kidney function
  13. Slide 15. Hemofiltration (HF) 1. Hemofiltration is a form of renal replacement therapy (RRT) in which plasma water and solutes are removed from blood by ultrafiltration through a semipermeable membrane, and the filtered fluid is replaced with a substitution (replacement) fluid. 2. Unlike hemodialysis, dialysate is not primarily used, and solute removal occurs mainly by convection. 3. Hemofiltration works mainly on: 1. Ultrafiltration 2. Convection (solvent drag) 4. Mechanism: 1. A hydrostatic pressure gradient forces plasma water across a highly permeable membrane 2. Solutes are carried along with water (convection) 3. Larger molecules (up to ~20,000–30,000 Daltons) can be removed more effectively than in diffusion-based dialysis 5. No significant role of diffusion (since dialysate is absent or minimal)
  14. Slide 16. Procedure of Hemofiltration 1. Vascular access is established (venous or arterial-venous) 2. Blood is withdrawn from the patient 3. Blood is passed through a hemofilter (high-permeability membrane) 4. Ultrafiltrate (fluid + solutes) is removed 5. Replacement fluid (sterile electrolyte solution) is infused: Either before (pre- dilution) or After (post-dilution) the filter 6. Filtered blood is returned to the patient  Blood flow is usually pump-driven (especially in venovenous methods)
  15. Slide 17. Feature CVVH (Venovenous) CAVH (Arteriovenous) Pathway Vein → filter → vein Artery → filter → vein Driving force Pump Arterial pressure Pump required Yes No Use Common (ICU) Rare Vascular Access Routes
  16. Slide 18. Type Key Features Clinical Use / Notes Intermittent Hemofiltration Performed for short sessions; Similar to intermittent hemodialysis Used less commonly Continuous Venovenous Hemofiltration (CVVH) Access via dual-lumen venous catheter; Blood flow maintained using a pump; Continuous (24- hour) therapy Most commonly used in ICU Continuous Arteriovenous Hemofiltration (CAVH) Blood drawn from artery (e.g., femoral artery) and returned to vein; Flow driven by arterial pressure (no pump required) Rarely used now Types of Hemofiltration
  17. Slide 19. Advantages of Hemofiltration Disadvantages of Hemofiltration Continuous and gradual fluid removal More complex than standard hemodialysis Better hemodynamic stability (ideal for ICU patients) Expensive (equipment and replacement fluids) Precise control of fluid balance Requires continuous monitoring Effective electrolyte regulation Risk of infection (vascular access) Better removal of middle and larger molecules Risk of thrombosis Useful in critically ill patients Requires trained personnel
  18. Slide 20. Hemodiafiltration (HDF)  Hemodiafiltration is a renal replacement therapy that combines the principles of hemodialysis and hemofiltration, allowing removal of both: 1. Small molecular weight solutes (via diffusion) 2. Middle and larger molecular weight solutes (via convection)  It is considered an advanced form of dialysis with improved solute clearance.
  19. Slide 21.  Principle of Hemodiafiltration: HDF works through a combination of two mechanisms: 1. Diffusion: Movement of solutes from high → low concentration Efficient for: Urea, Creatinine, Electrolytes 2. Convection (Solvent Drag): Solutes are removed along with fluid movement Effective for: Middle and large molecules (e.g., β2-microglobulin) 3. Ultrafiltration: A pressure gradient is applied to remove large volumes of fluid Lost fluid is replaced with sterile substitution fluid Thus, HDF provides: High-efficiency clearance of a wide range of solutes
  20. Slide 22. Procedure of Hemodiafiltration 1. Blood is withdrawn via vascular access 2. Blood passes through a high-flux dialyzer 3. Simultaneously: Dialysate flows for diffusion Ultrafiltration occurs for convection 4. Large volumes of plasma water are removed 5. Replacement fluid is infused: 6. Pre-dilution or post-dilution 7. Purified blood is returned to the patient
  21. Slide 23. Advantages of HDF Disadvantages of HDF Superior solute clearance Expensive (equipment + replacement fluid) Removes both small and middle molecules Requires high-quality ultrapure water Better removal of uremic toxins Needs specialized machines Improved hemodynamic stability More complex procedure Reduced complications (e.g., dialysis-related amyloidosis) Requires trained staff Better long-term outcomes (in some patients) Limited availability in some settings Improved quality of life
  22. Slide 24. Peritoneal Dialysis (PD) Peritoneal dialysis is a form of renal replacement therapy in which the peritoneal membrane acts as a semipermeable membrane, allowing removal of waste products, excess fluids, and electrolytes from the blood into a dialysis fluid instilled in the peritoneal cavity.
  23. Slide 25. Principle of Peritoneal Dialysis  PD works mainly through: Diffusion, Osmosis (Ultrafiltration)  Mechanism: The peritoneal membrane is highly vascular and semi-permeable  Solutes move from: Blood (higher concentration) → Dialysate (lower concentration) by diffusion  Fluid removal occurs due to: Osmotic gradient (created by glucose in dialysate)  Allows removal of: 1. Urea, creatinine 2. Electrolytes 3. Excess water  PD is preferred in: 1. Hemodynamically unstable patients (hypotension) 2. Patients with residual kidney function 3. Patients preferring home-based/self-care therapy
  24. Slide 26.  Structure of Peritoneal Membrane 1. Composed of: Mesothelial cells , Basement membrane , Interstitial tissue 2. Surface area: ~1–2 m² (similar to body surface area)  Peritoneal Dialysis Access: Indwelling peritoneal catheter (silastic, biocompatible) 1. Length: 40–45 cm 2. Positioned in pelvic cavity 3. Contains 1–2 cuffs: 1. Prevent infection 2. Provide stability 4. Exit site: Important for preventing infection 5. Maturation period: 2–6 weeks preferred
  25. Slide 27. Component Details Base Sterile water with electrolytes Electrolytes Sodium (~132 mEq/L), Chloride (~96 mEq/L), Calcium (2.5–3.5 mEq/L), Magnesium (0.5 mEq/L), Lactate (~40 mEq/L buffer) Osmotic Agents Dextrose (1.5%, 2.5%, 3.86%, 4.25%) or Icodextrin (7.5%) Function of Osmotic Agent Creates osmotic gradient → removes excess fluid (ultrafiltration) Osmolarity Hyperosmolar (dextrose solutions), Iso-osmolar (icodextrin) pH Slightly acidic (~5–6 in standard solutions; newer solutions closer to physiological ~7.3) Volume per exchange 1–3 liters  Peritoneal Dialysis Solutions
  26. Slide 28. Type Characteristics Dextrose-based solutions Most commonly used; effective ultrafiltration; may cause hyperglycemia and weight gain Icodextrin-based solutions Long-duration ultrafiltration; fewer metabolic effects; used for long dwell (8–16 hours) Biocompatible solutions Neutral pH, low glucose degradation products; better for peritoneal membrane
  27. Slide 29.  Procedure / Process of Peritoneal Dialysis 1. A soft catheter is surgically inserted into the peritoneal cavity 2. Sterile, warmed dialysate (1–2 liters) is infused into the abdomen 3. The fluid remains in the cavity for a fixed time (dwell period) 4. Waste products and fluid move into dialysate 5. The fluid is then drained into a collection bag  Phases of Peritoneal Exchange: Each cycle consists of: 1. Fill phase – Dialysate is infused 2. Dwell phase – Exchange of solutes and fluid occurs 3. Drain phase – Used dialysate is removed
  28. Slide 30. Feature CAPD (Continuous Ambulatory PD) APD (Automated PD) Method Manual exchanges by patient Machine-assisted (cycler) Common use Most commonly used Widely used (especially home therapy) Dwell time 4–8 hours Short cycles (night) + optional long daytime dwell Frequency 3–5 exchanges/day, daily (7 days/week) Multiple automated exchanges (usually overnight) Machine requirement Not required Required Portability Portable, flexible Less portable (machine dependent) Patient suitability Independent patients Patients needing assistance / prefer overnight dialysis Variants — Includes CCPD and other automated forms
  29. Slide 31. Category Complications Infectious Peritonitis (most important), Catheter-related infections Mechanical Catheter malfunction, Dialysate leakage, Hernias, Back pain Metabolic Weight gain (glucose absorption), Hyperglycemia, Protein and amino acid loss Others Inadequate ultrafiltration, Technique failure, Hemorrhoids
  30. Slide 32. Advantages of Peritoneal Dialysis Disadvantages of Peritoneal Dialysis Better hemodynamic stability (no rapid fluid shifts) Risk of peritonitis Preserves residual kidney function Protein loss through peritoneum No need for vascular access Continuous glucose absorption → obesity, hyperglycemia Can be done at home (independence, flexibility) Reduced appetite Less blood loss Mechanical complications: hernias, dialysate leaks, catheter problems No need for systemic heparinization Less efficient for rapid toxin removal (vs hemodialysis) Useful for all age groups Allows intraperitoneal drug administration

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