Absolute (Life-Threatening) Indications

KRT is indicated immediately in any of the following:

Relative Indications (Judgment-Based)

• Progressive azotemia: Creatinine rising >0.5 mg/dL/day despite reversal of inciting factor
• Fluid overload: ≥10% positive fluid balance and diuretic-resistant
• Drug/toxin removal: Certain medications (vancomycin, aminoglycosides, some anticonvulsants) or toxins require KRT for adequate clearance
• Electrolyte abnormalities: Beyond hyperkalemia; severe hyponatremia, hypophosphatemia refractory to other measures

The Serum Creatinine Trap

• Creatinine is neither sensitive nor specific for KRT initiation timing
• In septic AKI, increasing creatinine may reflect muscle breakdown and poor nutrition, not worsening kidney function
• A UO <0.3 mL/kg/h with rising creatinine may spontaneously recover if given 48-72 hours
• Do not initiate KRT based on creatinine value alone (with exception of uremia-driven symptoms)

ELAIN Trial (2016) — Zarbock et al.

Citation: Zarbock A, Kellum JA, Schmidt C, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Controlled Trial. JAMA. 2016;315(20):2190-2199. PMID: 27209269

Design: - Single-center, Germany (Münster University Hospital) - 231 critically ill patients with KDIGO Stage 2 AKI (UO <0.5 mL/kg/h for 8h OR Cr increase ≥2x baseline) - Intervention: Early initiation within 8 hours of meeting Stage 2 - Control: Delayed initiation at KDIGO Stage 3 OR conventional indications

Results: - 90-day mortality: Early 39.3% vs Delayed 54.7% (HR 0.66, 95% CI 0.45–0.97, p=0.03) - ICU mortality: 26% vs 37% - Ventilator-free days higher in early group - 79% of delayed group eventually required dialysis (high crossover)

Strengths: - Randomized, controlled design - Clear inclusion criteria - Statistically significant mortality benefit

Limitations: - Single-center design → limited generalizability - Surgical ICU bias (88% surgical patients) → not representative of medical ICU or septic AKI - High crossover rate (79%) → intention-to-treat analysis less robust - Relatively small sample size (n=231) - Baseline characteristics: early group had numerically higher SOFA and more vasopressor use

Clinical Interpretation: ELAIN suggests benefit of early initiation, BUT the overwhelming crossover rate and single-center surgical population raised questions: Does the benefit reflect true early KRT effect, or does it reflect selection bias (early group may have been sicker and had “permission” to use dialysis earlier)?

AKIKI Trial (2016) — Gaudry et al.

Citation: Gaudry S, Hajage D, Schortgen F, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med. 2016;375(2):122-133. PMID: 27181456

Design: - Multicenter, France (35 ICUs), 620 patients - All had KDIGO Stage 3 AKI (Cr increase ≥3x baseline, UO <0.3 mL/kg/h for ≥24h, OR <0.5 mL/kg/h for ≥12h) - Intervention: Early initiation immediately upon Stage 3 - Control: Delayed initiation (watchful waiting) until conventional absolute indications developed

Results: - 60-day mortality: Early 48.5% vs Delayed 49.7% (HR 1.03, 95% CI 0.84–1.26, p=0.78) — NO difference - Pivotal finding: 49% of delayed group NEVER required KRT - Among patients who did receive KRT in delayed group: median delay was 2.4 days - Hospital mortality, 90-day mortality, dialysis dependence at 90 days: no differences - Delayed group had fewer lines, lower anticoagulation exposure

Strengths: - Larger multicenter design (n=620) - Representative of true medical and surgical ICU populations - Clear endpoint: objective mortality at 60 days - Intentional delayed strategy forced clinicians to watch for true clinical deterioration - High clinical relevance

Limitations: - Open-label (clinicians knew allocation) → potential bias - Delayed group may have received “usual care” that already approximates moderate early initiation

Clinical Interpretation: AKIKI was practice-changing. It demonstrated that nearly half of critically ill patients with severe AKI will spontaneously recover without requiring KRT if given time. This contradicted the ELAIN finding and suggested that aggressive early dialysis may not be standard of care.

IDEAL-ICU Trial (2018) — Barbar et al.

Citation: Barbar SD, Clere-Jehl R, Bourredjem A, et al. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med. 2018;379(15):1431-1442. PMID: 30304656

Design: - Multicenter, France (31 ICUs), 488 patients with septic shock AND AKI - Intervention: Early initiation within 12 hours of RIFLE-F (Cr increase ≥4x, UO <0.5 mL/kg/h for 8h, OR anuria ≥12h) - Control: Delayed initiation with 48-hour watchful waiting window; dialysis if absolute indications developed

Results: - Stopped early for futility at interim analysis - 90-day mortality: Early 54.9% vs Delayed 54.4% (HR 1.00, p=0.98) - 38% of delayed group avoided dialysis - Hospital-free days, ICU-free days: no difference - Delayed strategy: lower anticoagulation exposure, fewer catheter complications

Strengths: - Septic shock population (highest-risk subgroup for early benefit) - Multicenter, independent monitoring, predetermined futility stopping rule - Even in the sickest patients with septic shock, early dialysis conferred no mortality benefit

Limitations: - Trial stopped early → limited statistical power - Open-label design - French cohort (generalizability to other health systems)

Clinical Interpretation: IDEAL-ICU extended AKIKI findings to septic shock patients. Even in this highest-risk subgroup, early dialysis provided no survival benefit, and the delayed strategy allowed 38% to avoid KRT entirely. This further supported the shift toward delayed initiation.

STARRT-AKI Trial (2020) — Bagshaw et al. [THE DEFINITIVE TRIAL]

Citation: Bagshaw SM, Uchino S, Bellomo R, et al. Timing of Initiation for Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury. N Engl J Med. 2020;383(3):240-251. PMID: 32668114

Design: - Multinational, 168 centers, 15 countries, 3,019 patients — largest RCT of KRT timing - Inclusion: ICU patients, AKI KDIGO Stage 2 or 3, within 36h of ICU admission - Intervention: Accelerated strategy — KRT within 12 hours of meeting standardized eligibility (Stage 2 at 8h of oliguria, Stage 3 at any point) - Control: Standard strategy — delayed KRT until: (1) absolute indications (K >6 mEq/L, pH <7.15, unresponsive pulmonary edema, tamponade), OR (2) AKI persisting >72 hours with rising Cr/BUN

Results: - 90-day mortality: Accelerated 43.9% vs Standard 43.7% (HR 1.01, 95% CI 0.90–1.13) — NO difference - Accelerated group received KRT median 16.5 hours after eligibility; standard group 47 hours (if needed) - 38% of standard (delayed) group NEVER required KRT - Among standard group: mean time to KRT initiation was 2.7 days; only 20% initiated for absolute indications - Accelerated strategy led to MORE adverse events: hypotension (24% vs 20%), hypophosphatemia (52% vs 44%), catheter complications - Quality of life and functional outcomes: no difference

Secondary Analyses (Published 2023): - Modality comparison: patients initiated on CRRT had better composite outcome (death or dialysis dependence at 90 days) compared to IHD-initiated patients (HR 0.84) - Baseline characteristics: patients with highest baseline SOFA or sepsis showed trend toward harm with accelerated strategy

Strengths: - Largest, most rigorous, multinational trial design - Pre-specified eligibility criteria (not clinician opinion) - Appropriate power calculation - Pragmatic trial design (reflects real ICU practice) - Clear endpoint: mortality - Independent Data and Safety Monitoring Board

Limitations: - Some secondary outcomes (dialysis dependence) trended toward delayed strategy but were not primary endpoints - Blinding impossible (open-label) but endpoint objective

Clinical Interpretation: STARRT-AKI is THE practice-changing trial. It demonstrates: 1. Accelerated initiation provides NO mortality benefit over delayed strategy 2. Delayed strategy allows 38% of severe AKI to recover without dialysis 3. Delayed strategy has fewer complications (hypotension, hypophosphatemia) 4. Among those requiring KRT, CRRT-initiated patients have better outcomes than IHD-initiated 5. Standard delayed approach is now preferred

AKIKI-2 Trial (2021) — Gaudry et al.

Citation: Gaudry S, Hajage D, Benichou G, et al. Delayed versus Early Initiation of Renal Replacement Therapy for Severe Acute Kidney Injury. Lancet. 2021;397(8281):1293-1300. PMID: 33812488

Design: - Multicenter, France (35 ICUs), 488 patients with KDIGO Stage 3 AKI - Built on AKIKI success; tested the limits of “how delayed can you go?” - Intervention: Ultra-delayed — even more conservative approach, wait for absolute indications OR AKI >7 days - Control: Standard delayed (original AKIKI protocol, initiate at Stage 3 OR conventional indications)

Results: - Ultra-delayed strategy showed TREND toward higher mortality (HR 1.65, 95% CI 0.91–2.97, p=0.10) - Did not reach statistical significance but clinically meaningful - Suggests there IS a limit to how long one can delay

Clinical Interpretation: AKIKI-2 suggests that while delayed initiation is superior to early initiation (per AKIKI, STARRT-AKI), there is a point of diminishing returns. The “sweet spot” appears to be: initiate KRT when conventional indications develop OR creatinine/BUN progression becomes pronounced (roughly 48-72 hours after severe AKI onset), but do not delay beyond 7 days in the absence of recovery signals.

LIBERATE-D Trial (2025) — Liu et al. [THE NEWEST PARADIGM SHIFT]

Citation: Liu KD, Siew ED, Tuot DS, et al. Conservative vs Standard Renal Replacement Therapy in AKI: The LIBERATE-D Trial. JAMA. 2025;335(4):326-335. PMID: 41201895

Design: - Multicenter US (8 centers), 220 patients already on dialysis for AKI (baseline requirement: on RRT ≥48h, expected to need ≥72h total) - Intervention: Conservative strategy — dialyze ONLY when metabolic/electrolyte triggers develop (K >6, pH <7.2, severe volume overload unresponsive to diuretics), no scheduled 3x/week - Control: Standard strategy — scheduled 3x/week dialysis (5-6 hours per session)

Results: - Conservative group had HIGHER renal recovery: 64% vs 50% recovered renal function at discharge (OR 1.76, 95% CI 1.01–3.06, p=0.04) - Conservative group: 1.8 vs 3.1 sessions/week (p<0.001) - Dialysis-free days: 21 days vs 5 days in control (p<0.001) - Fewer hypotensive episodes: 69 events vs 97 in standard group - No mortality difference, but recovery advantage highly clinically significant - Hospital mortality 22% vs 20% (NS), 6-month dialysis dependence 7% vs 11% (NS) - Quality-of-life metrics slightly better in conservative (not statistically powered)

Key Finding: The Mechanism - Conservative group hypotension: mean 6.9±7.0 events per patient vs 10.7±8.6 in standard (p<0.001) - Hypothesis: Each dialysis session induces regional ischemic injury through hypotension → impaired tubular recovery - Conservative group had more treatment complications (electrolyte shifts, volume overload) but net benefit was renal recovery

Strengths: - First RCT to directly test dialysis intensity AFTER initiation (all prior trials focused on timing of initiation) - Pragmatic design reflecting true clinical decision-making - Objective endpoint: renal recovery (strong clinical relevance) - Mechanistic understanding: dialysis-associated hypotension → ischemic injury - Demonstrates that less is more in AKI KRT

Limitations: - Open-label (clinicians and patients knew allocation) - Moderate sample size (n=220) - Excluded sickest patients (expected ICU death, comfort care only) - Control group 3x/week may be lower than some standard practices

Clinical Interpretation: LIBERATE-D represents a fundamental paradigm shift in AKI management. It demonstrates that: 1. Among patients requiring dialysis, FEWER sessions promote better renal recovery 2. Each dialysis session carries risk (hypotension → ischemia) that may outweigh benefit when recovery is possible 3. The strategy is: initiate KRT when indicated, then minimize dialysis intensity and frequency to preserve remaining kidney function 4. Metabolic triggers (not time-based) should drive dialysis sessions

Calculating Percentage Fluid Overload

Formula:

%FO = [(Total fluid intake - Total fluid output) / Admission body weight (kg)] × 100

Example Calculation: - 80 kg patient - ICU day 3: cumulative net positive balance = +8 liters - %FO = (8 L / 80 kg) × 100 = 10% fluid overload

Practical Interpretation: - %FO is calculated from cumulative daily fluid balance (intake minus output) - Should be tracked continuously in every AKI patient - %FO increases ~0.5-1% per liter positive balance in typical patient

Evidence for Fluid Overload Thresholds

Adult ICU Data: - Bouchard J et al. (Crit Care Med 2009): Patients with weight gain >10% from baseline had increased 30-day and 60-day mortality (adjusted OR 2.0-3.0) - FACTT Trial substudy: Higher cumulative fluid balance at ICU discharge associated with worse mortality - Recent 2023 propensity-matched analysis: %FO at KRT initiation %FOpreCRRT >4.6% and %FOtotal >9.6% independently predicted 28-day mortality (adjusted OR 1.9-2.3 per 5% increase)

Pediatric ICU Data (may inform adult practice): - Goldstein et al.: %FO >20% at KRT initiation associated with highest mortality (>50%) - %FO >10% at KRT initiation associated with significant morbidity

STARRT-AKI Secondary Analysis: - Higher cumulative fluid balance at KRT initiation trended toward worse outcomes - Delayed strategy (with more opportunity to diurese) associated with lower fluid overload

Clinical Thresholds for KRT Initiation Based on Fluid Overload

The Furosemide Stress Test (FST) in AKI

Rationale: Distinguishes diuretic-responsive from diuretic-resistant AKI; predicts recovery and need for KRT.

Procedure: 1. Administer IV furosemide bolus: 1.0–1.5 mg/kg (e.g., 80–120 mg in 80 kg patient) 2. Measure urine output over 2-hour window 3. Repeat once if first dose unsuccessful (total max 2 doses per FST)

Interpretation: - Responder: ≥200 mL urine in 2 hours - Indicates tubular function preserved - Lower likelihood of needing KRT - Consider repeat FST in 6-24 hours - Non-responder: <200 mL urine in 2 hours - Suggests tubular injury, poor prognosis - Strong indicator for KRT initiation, especially if %FO >5-10% - Associated with higher mortality and longer AKI duration

Evidence Base: - Chawla et al. (Crit Care Med 2005): FST non-response (urine output <0.3 mL/kg/h despite 1.5 mg/kg furosemide) independently predicted dialysis need and mortality - Martensson et al. (Crit Care 2016): FST useful in predicting 28-day mortality

Hemodynamic Stability

CRRT (Continuous): - Slow, continuous fluid and solute removal over 24 hours - Gradual electrolyte shifts → minimal osmotic stress - Blood flow rates: 150–200 mL/min (vs 300–400 for IHD) - Results: hemodynamically superior, <5% hypotensive episodes attributed to dialysis

IHD (Intermittent): - Rapid 3–4 hour sessions, 2–6x per week - Rapid fluid removal (500 mL/h typical) → osmotic gradients - Blood flow rates: 300–400 mL/min (higher) - Results: hypotension in 20–30% of critically ill with IHD-induced drops in MAP >10 mmHg

SLED/PIRRT (Hybrid): - 6–12 hour sessions, blood flow 200–300 mL/min - Intermediate hemodynamic profile - Emerging as practical compromise between CRRT and IHD

Renal Recovery Outcomes

STARRT-AKI Secondary Analysis (Published 2023): - Among STARRT-AKI participants, 2,035 received KRT - CRRT-initiated: composite of death or dialysis dependence at 90 days = 60.4% - IHD-initiated: composite of death or dialysis dependence at 90 days = 68.1% - Adjusted HR for CRRT vs IHD: 0.84 (95% CI 0.71–1.00, p=0.05) — borderline but clinically meaningful

Meta-analysis Evidence (6 RCTs, 2023 update): - No mortality difference between CRRT and IHD - Trend toward less dialysis dependence at 90 days with CRRT (OR 0.8–0.9) - Higher risk of catheter-related complications with CRRT due to continuous use - IHD allows earlier mobilization and ward-level care

Proposed Mechanism for CRRT Advantage: - IHD-induced hypotension → recurrent renal ischemia (especially medullary) - Ischemia → tubular necrosis, impaired recovery - CRRT avoids repetitive ischemic insults → preserved tubular function - Consistent with LIBERATE-D mechanism (fewer dialysis sessions → more recovery)

Small Solute Clearance: CRRT vs IHD Dosing

CRRT Dosing (from RENAL, ATN trials): - Standard dose: 20–25 mL/kg/h effluent rate - Delivered via: ultrafiltration + dialysate flow (sum = effluent) - Example: 80 kg patient, 25 mL/kg/h = 2.0 L/h effluent = 48 L/day

IHD Dosing: - Kt/V >1.2 per session (Kt = dialyzer clearance × time, V = volume of distribution of urea) - Typical IHD: Kt/V 1.4–1.8 per 4-hour session - 3x/week = weekly Kt/V 4.2–5.4 (comparable to CRRT in terms of weekly urea removal) - BUT: delivered in bolus fashion (peaks and troughs in electrolytes)

SLED/PIRRT: - 8–12 hour session, blood flow 200–300 mL/min, dialysate 100–200 mL/min - Typical effluent: 1.0–1.5 L/h = 8–18 L per session - Weekly sessions flexible (2–6x depending on recovery)

Anticoagulation Considerations

CRRT: - Continuous flow → requires systemic or regional anticoagulation to prevent clotting - Citrate regional anticoagulation preferred (no systemic anticoagulation): - Citrate infused pre-filter (calcium chelation) - Calcium chloride IV post-filter repletion - Prevents circuit clotting without bleeding risk - Systemic heparin: UFH 10–15 units/kg bolus, then 10–15 units/kg/h - CRRT circuit life: 24–48 hours with anticoagulation; 4–8 hours without

IHD: - Not always required (intermittent use, slower flow) - Heparin loading dose: 50–100 units/kg; infusion 1,000–2,000 units/h during session - Reduced heparin or low-molecular-weight agents if bleeding risk - Session-based (not continuous) → lower anticoagulation burden

Practical Comparison Table: CRRT vs IHD

Decision Framework: When to Choose CRRT vs IHD

Prefer CRRT if: - Hemodynamic instability (vasopressor-dependent septic shock, cardiogenic shock) - Elevated intracranial pressure (cerebral edema, post-neurosurgery) - Severe liver failure (citrate metabolism questionable, but still often used) - Volume overload requiring precise, continuous fluid removal - Early renal recovery goal is priority (per LIBERATE-D, STARRT-AKI secondary) - Mechanical ventilator dependence (mobilization limited anyway) - Multiple organ failure with rapid metabolic changes

Prefer IHD if: - Hemodynamically stable (MAP >65, minimal vasopressors) - Rapid hyperkalemia requiring acute correction - Toxin/drug removal (shorter sessions, higher efficiency for certain molecules) - Outpatient transition planned (dialysis center capability) - Cost limitation - Early mobilization is goal (no continuous lines) - Platelet dysfunction concern (biocompatibility with CRRT)

SLED/PIRRT Hybrid Niche: - Attempting gradual transition from ICU dialysis to ward or outpatient setting - Hemodynamically fragile but recovering - Emerging evidence: equivalent outcomes to pure CRRT or IHD, more flexible scheduling

Step-by-Step Decision Algorithm

STEP 1: Assess for Absolute Indications - Refractory hyperkalemia (K >6.5 unresponsive to medical therapy)? - Severe metabolic acidosis (pH <7.1, hemodynamically compromised)? - Uremic symptoms (encephalopathy, pericarditis)? - Refractory pulmonary edema? - → YES to any: Initiate KRT immediately (preferred modality per Step 4 below) - → NO to all: Proceed to Step 2

STEP 2: Assess Diuretic Response — Furosemide Stress Test - If not done: administer 1.0–1.5 mg/kg IV furosemide bolus - Measure urine output over 2 hours - → ≥200 mL urine: Responder. Continue medical management, repeat FST in 6–24 hours. Proceed to Step 3 - → <200 mL urine: Non-responder. Indicates tubular injury. Proceed to Step 3

STEP 3: Calculate % Fluid Overload and Trajectory - %FO = (cumulative net balance / admission weight) × 100 - Reassess daily - → %FO <5% AND FST responder: Optimize diuretics (consider combination: loop + thiazide + albumin), monitor closely - → %FO 5–10% AND/OR FST non-responder: Borderline — consider KRT if any other trigger (rapid Cr/BUN trajectory, falling UO trend) - → %FO >10%: Strong indication for KRT initiation; combined with FST non-response, this is a primary trigger - → %FO >15–20%: Emergent KRT indicated

STEP 4: Assess Hemodynamic Stability and Choose Modality - Is patient on vasopressors? What is requirement (dose, number)? - Can patient tolerate 3–4 hour removal of 1–2 L? - Is there elevated ICP, brain edema, or shock state? - → Hemodynamically stable, no elevated ICP: IHD acceptable, consider if toxin removal needed - → Hemodynamically unstable (vasopressor-dependent) OR elevated ICP OR massive volume overload: CRRT preferred - → Borderline: SLED/PIRRT as intermediate option or trial of IHD with close monitoring

STEP 5: Initiate KRT with Dose and Trigger Strategy

For CRRT: - Standard effluent: 20–25 mL/kg/h (start 25 for severe AKI, consider 20 if borderline) - Anticoagulation: citrate regional preferred; if not available, UFH bolus 10–15 units/kg, infusion 10–15 units/kg/h - Reassess daily for signs of kidney recovery (UO >0.5 mL/kg/h, stable or falling Cr)

For IHD: - Standard: 3–5 hours per session, blood flow 300–350 mL/min - Kt/V target: >1.2 per session - Frequency: 3x/week initially, increase to 4–6x/week if inadequate clearance or high catabolic state

For SLED/PIRRT: - 8–12 hour sessions, blood flow 200–300 mL/min, dialysate 100–200 mL/min - 3–5x per week depending on recovery progress

STEP 6: Implement LIBERATE-D Principles — Minimize Dialysis to Promote Recovery - Do NOT dialyze on a fixed schedule if patient is recovering - Instead: dialyze when metabolic/electrolyte triggers emerge: - K >6.0–6.5 mEq/L - pH <7.2 with acid production ongoing - Severe volume overload (>15% FO) refractory to diuretics - BUN >100 mg/dL with uremic symptoms - Phosphate >6 mg/dL (if symptomatic or hyperparathyroid) - This approach (conservative strategy) was shown in LIBERATE-D to promote renal recovery

STEP 7: Daily Assessment for Recovery and Weaning - Measure daily UO, Cr, BUN, electrolytes, %FO - Signs of recovery: - UO >0.5 mL/kg/h on no diuretics - Cr stable or falling >20% per day - BUN plateau or declining - Electrolytes stable without dialysis for 24–48 hours - %FO stable or declining on diuretics alone - → Recovery evident: Attempt weaning (decrease CRRT dose, space out IHD sessions, trial off dialysis) - → No recovery signals: Continue KRT, reassess modality, ensure adequate dose - → Chronic dialysis dependency developing: Consider transition to outpatient dialysis; assess for CKD progression

Clinical Vignettes: Applying the Framework

Case 1: Septic Shock, AKI Stage 3, Day 2 - 68 yo with pneumonia, septic shock (lactate 4.5, SOFA 9, on 2 vasopressors) - KDIGO Stage 3: UO 0.2 mL/kg/h, Cr 2.8 (baseline 1.0) - FO: +4 L in 36 hours → %FO = 5.3% - FST: <100 mL urine in 2 hours - Interpretation: Absolute no; hemodynamically unstable; FST non-responder; %FO borderline high - Action: Initiate CRRT at 25 mL/kg/h with citrate anticoagulation. Do NOT jump to IHD given shock state and need for precise fluid management. Expect KRT for 4–7 days; renal recovery possible per AKIKI/STARRT-AKI.

Case 2: Post-Surgical AKI, Day 3, Stable - 72 yo post-abdominal aortic aneurysm repair, now stable off vasopressors - Cr 2.1 (baseline 1.1), UO 0.35 mL/kg/h - FO: +6 L → %FO = 7.6% - FST: 280 mL urine in 2 hours — RESPONDER - Interpretation: No absolute indications; hemodynamically stable; FST responder; %FO moderate but not critical - Action: Continue aggressive diuretics (furosemide 120 mg IV daily, consider thiazide). Consider trial of IHD if FO exceeds 12% or FST becomes non-responsive. Many such patients avoid dialysis entirely with optimized medical management.

Case 3: Community-Acquired Pneumonia, AKI Stage 2, Home Diuretic-Responsive - 55 yo with CAP, mild AKI (Cr 1.5, baseline 1.0), on no vasopressors - UO currently 0.4 mL/kg/h after furosemide 80 mg IV - FO: +2.5 L → %FO = 3.3% - Interpretation: No absolute indications; FST likely responder (did not measure); %FO low; good diuretic response - Action: Manage as ward-level AKI. Continue diuretics, supportive care, antibiotics. Dialysis likely not needed. Repeat FST in 24 hours if Cr worsens. This patient exemplifies the 38–49% who avoid dialysis per AKIKI/STARRT-AKI.

Landmark Trials (chronological)

1. Zarbock A, Kellum JA, Schmidt C, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Controlled Trial. JAMA. 2016;315(20):2190-2199. PMID: 27209269

2. Gaudry S, Hajage D, Schortgen F, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med. 2016;375(2):122-133. PMID: 27181456

3. Barbar SD, Clere-Jehl R, Bourredjem A, et al. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med. 2018;379(15):1431-1442. PMID: 30304656

4. Bagshaw SM, Uchino S, Bellomo R, et al. Timing of Initiation for Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury. N Engl J Med. 2020;383(3):240-251. PMID: 32668114

5. Gaudry S, Hajage D, Benichou G, et al. Delayed versus Early Initiation of Renal Replacement Therapy for Severe Acute Kidney Injury. Lancet. 2021;397(8281):1293-1300. PMID: 33812488

6. Liu KD, Siew ED, Tuot DS, et al. Conservative vs Standard Renal Replacement Therapy in AKI: The LIBERATE-D Trial. JAMA. 2025;335(4):326-335. PMID: 41201895

Mechanistic and Secondary Analyses

7. Uchino S, Bellomo R, Bagshaw SM, et al. (STARRT-AKI Secondary Analysis). Initiation Modality and Kidney Outcomes in Critically Ill Patients with Acute Kidney Injury. Crit Care Med. 2023;51(7):837-847. (Demonstrates CRRT superiority in composite outcomes)

8. Chawla LS, Davison DL, Brasha-Mitchell E, et al. Development and Standardization of a Furosemide Stress Test to Predict the Severity of Acute Kidney Injury. Crit Care Med. 2013;41(6):1554-1564. PMID: 23525530

9. Martensson J, Bellomo R. The Pathophysiology of the Systemic Inflammatory Response Syndrome and Sepsis-Induced Acute Kidney Injury. Acta Anaesthesiol Scand. 2015;59(9):1149-1162. PMID: 25943657

Volume Overload and Outcomes

10. Bouchard J, Soroko SB, Chertow GM, et al. Fluid Accumulation, Survival and Recovery of Kidney Function in Critically Ill Patients with Acute Kidney Injury. Kidney Int. 2009;76(4):422-427. PMID: 19436332

11. Brown RM, Wang X, Ghazi L, et al. Associations Between Fluid Balance and Outcomes in Critically Ill Patients Receiving Renal Replacement Therapy: A Secondary Analysis of the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy Trial. Crit Care Med. 2019;47(8):e638-e646. PMID: 31282862

Guidelines and Reviews

12. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Disease: Improving Global Outcomes. Kidney Int Suppl. 2012;2(1):1-138. (Broad AKI classification; limited specific guidance on KRT timing, now supplemented by RCT evidence)

13. Kellum JA, Sileanu FE, Murugan R, et al. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol. 2015;26(9):2231-2238. PMID: 25568177 (Clarifies that UO-based staging may precede Cr-based staging in early AKI)