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.

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.

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.

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.

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.

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.