2025 PACUPrep BCCCP Preparatory Course Renal Replacement Therapies (RRT) Renal Replacement Therapies in Critical Care
Foundational Principles of Renal Replacement Therapy

Foundational Principles of Renal Replacement Therapy

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Learning Objective

  • Describe the foundational principles of RRT, including indications, modalities, and mechanisms of clearance.

I. Introduction

Renal replacement therapy (RRT) provides extracorporeal support in acute kidney injury (AKI) to correct life-threatening acid–base, electrolyte, and volume derangements. Critical care pharmacists play a crucial role in guiding the timing of RRT initiation, selecting appropriate modalities, and adjusting pharmacotherapy to optimize patient outcomes.

  • RRT can reduce ICU mortality by stabilizing hemodynamics and metabolic profiles in critically ill patients with severe AKI.
  • Pharmacists contribute by integrating laboratory trends, patient-specific factors, and multidisciplinary input to recommend timely and appropriate RRT initiation.
Key Pearls
  • Use the AEIOU mnemonic (Acidosis, Electrolytes, Intoxications, Overload, Uremia) for rapid screening of RRT indications, but always apply clinical judgment to the individual patient scenario.
  • Early pharmacy-led AKI surveillance and intervention can expedite nephrology consultation and appropriate RRT initiation when warranted.

Case Example: A 65-year-old septic patient develops refractory hyperkalemia (K⁺ 6.8 mEq/L) despite medical management with insulin and albuterol. The critical care pharmacist recommends immediate RRT based on the “E” (Electrolytes) criterion of the AEIOU mnemonic.

II. Indications for RRT

Indications for initiating RRT fall into absolute (often remembered by the AEIOU mnemonic) and relative categories. These guide the urgency of RRT, distinguishing between emergent and elective initiation.

Absolute Indications (AEIOU)

  • Acidemia: Severe metabolic acidosis (e.g., arterial pH < 7.20 or serum bicarbonate < 15 mEq/L) refractory to medical therapy.
  • Electrolytes: Life-threatening electrolyte abnormalities, most commonly refractory hyperkalemia (e.g., K⁺ > 6.5 mEq/L or K⁺ > 5.5 mEq/L with ECG changes) unresponsive to medical management.
  • Intoxications: Removal of certain dialyzable toxins or drugs (e.g., salicylates, lithium, methanol, ethylene glycol, metformin in severe lactic acidosis).
  • Overload: Life-threatening fluid overload (e.g., pulmonary edema) causing respiratory compromise and refractory to diuretic therapy.
  • Uremia: Symptomatic uremia, such as uremic pericarditis, pleuritis, encephalopathy, or unexplained bleeding diathesis.

Relative Indications

  • Progressive azotemia (rising BUN and creatinine) despite conservative measures, especially if associated with early uremic symptoms.
  • Refractory volume overload that is not immediately life-threatening but is unresponsive to diuretics and contributing to organ dysfunction.
  • Severe acid–base or electrolyte disturbances that are approaching critical thresholds and are difficult to manage medically.
Key Pearls
  • While AEIOU criteria are clear triggers for considering RRT, the decision must be balanced against potential risks such as bleeding (especially with anticoagulation needs for CRRT), hemodynamic instability during IHD, and resource availability.
  • When initiating RRT for relative indications, it is crucial to document the rationale clearly to support multidisciplinary consensus and ensure appropriate use of resources.

III. RRT Modalities Comparison

The main RRT modalities—Intermittent Hemodialysis (IHD), Prolonged Intermittent Renal Replacement Therapy (PIRRT, also known as Sustained Low-Efficiency Dialysis or SLED), and Continuous Renal Replacement Therapy (CRRT)—differ significantly in their clearance kinetics, session duration, and hemodynamic impact.

Comparison of Common RRT Modalities
Modality Mechanism of Clearance Duration/Schedule Advantages Disadvantages
IHD (Intermittent Hemodialysis) Primarily high-efficiency diffusion 3–5 hour sessions, typically 3–7 times per week Rapid solute and fluid removal; predictable scheduling; lower anticoagulation needs typically. Higher risk of hypotension; potential for disequilibrium syndrome; intermittent nature.
PIRRT/SLED (Prolonged Intermittent RRT / Sustained Low-Efficiency Dialysis) Hybrid: efficient diffusion and some convection; slower rates than IHD 6–12 hour sessions, often daily or several times per week Improved hemodynamic tolerance compared to IHD; effective solute removal over longer period. Increased nursing time and resource use compared to IHD; may still require anticoagulation.
CRRT (Continuous Renal Replacement Therapy) Continuous diffusion, convection, or both, depending on submodality 24 hours per day, continuous Superior hemodynamic stability; precise volume and metabolic control; sustained solute removal. Usually requires continuous anticoagulation; intensive monitoring; higher cost; patient immobilization.
Key Pearls
  • Reserve IHD for hemodynamically stable patients requiring rapid correction of electrolytes or fluid overload, or for toxin removal where rapid clearance is beneficial.
  • PIRRT/SLED serves as a valuable bridge between IHD and CRRT, particularly when CRRT resources are limited or when patients can tolerate longer, slower sessions better than IHD but do not require 24/7 therapy.
  • CRRT is generally preferred for hemodynamically unstable patients (e.g., those in shock requiring vasopressors) or patients with severe acute respiratory distress syndrome (ARDS) and significant fluid overload, or those with acute brain injury where fluid shifts must be minimized.

IV. Mechanisms of Solute and Fluid Removal

Solute and fluid removal during RRT rely on several physicochemical principles: diffusion, convection, and ultrafiltration. Each mechanism is suited to removing specific types of molecules and achieving particular clinical goals.

  • Diffusion: Solutes move across a semipermeable membrane from an area of higher concentration to an area of lower concentration (down their concentration gradient). This is most effective for removing small molecules like urea, creatinine, and potassium. Clearance is influenced by blood flow rate, dialysate flow rate, filter surface area, and membrane permeability.
  • Convection: Solutes are “dragged” across the semipermeable membrane with the flow of plasma water (solvent drag) that is being removed by ultrafiltration. This mechanism is more effective for removing middle to large molecules, such as inflammatory mediators (cytokines) and some protein-bound drugs. Convective clearance is primarily determined by the ultrafiltration rate and the sieving coefficient of the membrane for a given solute.
  • Ultrafiltration: Fluid (plasma water) is removed from the blood across the semipermeable membrane due to a transmembrane pressure gradient (hydrostatic or osmotic). This is the primary mechanism for achieving precise fluid balance and removing excess volume from the patient.
Key Pearls
  • Increasing blood flow rate (Qb) or dialysate flow rate (Qd) primarily enhances diffusive clearance of small solutes.
  • Utilizing membranes with larger pore sizes (high-flux membranes) and prescribing higher ultrafiltration volumes (often coupled with replacement fluid in convective therapies) enhances convective removal of middle and larger molecules.

V. CRRT Submodalities

Continuous Renal Replacement Therapy (CRRT) encompasses several modes, primarily Continuous Venovenous Hemofiltration (CVVH), Continuous Venovenous Hemodialysis (CVVHD), and Continuous Venovenous Hemodiafiltration (CVVHDF). These differ by the primary mechanism of solute clearance and how fluids are managed, allowing for therapy tailored to specific patient needs.

Comparison of Common CRRT Submodalities
Mode Primary Clearance Mechanism(s) Fluids Used Primary Solute Spectrum Removed Common Clinical Indications/Goals
CVVH (Continuous Venovenous Hemofiltration) Convection Replacement fluid (pre- or post-filter) Middle to large molecules (e.g., cytokines, myoglobin) effectively; also small molecules. Sepsis with high inflammatory burden; rhabdomyolysis; precise fluid overload control.
CVVHD (Continuous Venovenous Hemodialysis) Diffusion Dialysate Primarily small molecules (e.g., urea, creatinine, electrolytes). Efficient small solute clearance with excellent hemodynamic stability; managing severe azotemia or electrolyte imbalances.
CVVHDF (Continuous Venovenous Hemodiafiltration) Combined: Convection and Diffusion Dialysate and Replacement fluid Broad spectrum of small, middle, and large molecules. Patients with complex metabolic derangements; mixed toxin loads; situations requiring both efficient small molecule and enhanced middle molecule clearance.
Key Pearls
  • Choose CVVH when the primary goal is removal of inflammatory mediators or larger toxins, or when high-volume fluid exchange is desired. The rate of replacement fluid administration dictates the convective clearance.
  • Use CVVHD for efficient small-molecule removal with minimal net fluid shifts if desired, focusing on metabolic control. Dialysate flow rate is the main driver of diffusive clearance.
  • CVVHDF offers the most flexibility, allowing customization of both dialysate and replacement fluid rates to tailor diffusive and convective clearance according to specific patient needs.

VI. Clinical Integration and Decision Algorithm

The selection of an appropriate RRT modality is a critical decision that integrates the patient’s hemodynamic status, specific solute and fluid clearance goals, and available institutional resources. A structured approach can aid in this decision-making process.

Stepwise Modality Selection Framework:

  1. Assess hemodynamic stability: Evaluate mean arterial pressure (MAP), vasopressor requirements, and overall cardiovascular status. Is the patient stable or unstable?
  2. Define solute removal and fluid balance goals:
    • What types of solutes need to be removed (small molecules like urea/potassium vs. middle/large molecules like cytokines)?
    • Is rapid or gradual correction preferred?
    • What is the target fluid balance (net removal, even, or addition)?
  3. Evaluate available resources: Consider equipment availability (IHD machines, CRRT machines), nursing staff expertise and staffing ratios, and availability of appropriate RRT fluids.
  4. Select modality based on assessment:
    • Hemodynamically unstable patients: Generally favor CRRT for its gentle and continuous nature.
    • Hemodynamically stable patients: IHD or PIRRT may be appropriate.
      • IHD for rapid correction if tolerated.
      • PIRRT if slower, more sustained therapy is desired or if IHD is poorly tolerated but CRRT is not strictly necessary or available.
  5. Document the plan and communicate: Clearly document the chosen modality, rationale, initial prescription parameters, and monitoring plan. Communicate this effectively within the interdisciplinary team during rounds and handoffs.
RRT Modality Selection Algorithm Flowchart depicting the stepwise process for selecting an RRT modality. It starts with assessing hemodynamic stability, defining goals, and evaluating resources. This leads to a decision point for modality selection: unstable patients typically receive CRRT, while stable patients may receive IHD or PIRRT. The process concludes with documenting the plan and communication. 1. Assess Hemodynamic Stability(MAP, vasopressor dose, cardiac function) 2. Define Solute & Fluid Goals(small/middle molecules; rapid/gradual; fluid balance) 3. Evaluate Resources & Logistics(equipment, staffing, anticoagulation needs) 4. Select Modality Hemodynamically Unstable Hemodynamically Stable CRRT IHD or PIRRT/SLED(based on goals, tolerance, scheduling) 5. Document Plan & Communicate(Prescription, monitoring, interdisciplinary rounds)
Figure 1: Stepwise RRT Modality Selection Algorithm. This flowchart outlines a structured approach to choosing an RRT modality, considering patient stability, therapeutic goals, and available resources, culminating in a documented and communicated plan.
Key Pearls
  • Align the RRT modality choice with specific patient comorbidities (e.g., CRRT is often preferred in acute brain injury to minimize osmotic shifts, or in severe ARDS for precise fluid management) and ICU logistical considerations.
  • Developing and implementing standardized institutional protocols for RRT initiation, modality selection, and management can help reduce practice variability, improve safety, and optimize resource utilization.

References

  1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117–S314.
  2. Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury. Am J Kidney Dis. 2013;61(5):649-672.
  3. Villa G, Ricci Z, Ronco C. Renal replacement therapy. Crit Care Clin. 2015;31(4):855-866.
  4. See EJ, Bellomo R. Acute kidney injury: an overview of renal replacement therapy. Crit Care Resusc. 2011;13(2):124-131.
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