Acute Kidney Injury and Acute-on-Chronic Kidney Disease in Critical Care: A Contemporary Review

Dr Neeraj Manikath , claude.ai

Abstract

Background: Acute kidney injury (AKI) affects 20-50% of critically ill patients and carries significant mortality risk. The intersection of AKI with pre-existing chronic kidney disease (CKD) creates complex pathophysiological scenarios requiring nuanced management approaches.

Objective: To provide critical care physicians with evidence-based strategies for diagnosis, classification, and management of AKI and acute-on-chronic kidney disease, emphasizing practical clinical pearls and contemporary therapeutic approaches.

Methods: Comprehensive review of recent literature, international guidelines, and expert consensus statements on AKI management in critical care settings.

Conclusions: Early recognition using novel biomarkers, aggressive hemodynamic optimization, and judicious use of renal replacement therapy remain cornerstones of management. Emerging therapies show promise for improving outcomes in this high-risk population.

Keywords: Acute kidney injury, chronic kidney disease, critical care, renal replacement therapy, biomarkers

Introduction

Acute kidney injury represents one of the most challenging clinical scenarios in intensive care medicine. The traditional view of AKI as a reversible condition has evolved to recognize its complex pathophysiology and long-term consequences. When superimposed on chronic kidney disease, the clinical picture becomes even more intricate, requiring sophisticated diagnostic and therapeutic approaches.

The KDIGO (Kidney Disease: Improving Global Outcomes) definition has standardized AKI classification, yet significant challenges remain in early detection, appropriate intervention timing, and outcome optimization. This review synthesizes current evidence to provide critical care practitioners with actionable insights for managing these complex patients.

Epidemiology and Definitions

AKI Classification (KDIGO 2012)

Stage 1: Serum creatinine increase ≥0.3 mg/dL within 48 hours OR 1.5-1.9× baseline within 7 days OR urine output <0.5 mL/kg/hr for 6-12 hours

Stage 2: Serum creatinine 2.0-2.9× baseline OR urine output <0.5 mL/kg/hr for ≥12 hours

Stage 3: Serum creatinine ≥3.0× baseline OR increase to ≥4.0 mg/dL OR initiation of RRT OR urine output <0.3 mL/kg/hr for ≥24 hours OR anuria for ≥12 hours

🔍 Clinical Pearl #1: The "Creatinine Blind Spot"

Serum creatinine is a lagging indicator—by the time it rises significantly, 50% of kidney function may already be lost. In critically ill patients with fluctuating volume status and muscle mass, this delay is even more pronounced.

Pathophysiology: Beyond Hemodynamics

Traditional Paradigm

The classical prerenal-intrinsic-postrenal classification, while useful, oversimplifies the complex pathophysiology of critical illness-associated AKI.

Contemporary Understanding

Sepsis-Associated AKI: Combines hemodynamic instability, inflammatory cytokine release, and microcirculatory dysfunction
Cardiorenal Syndrome: Type 1 (acute cardiac dysfunction causing AKI) and Type 3 (AKI causing acute cardiac dysfunction)
Hepatorenal Syndrome: Functional AKI in advanced liver disease with preserved kidney histology

💎 Clinical Pearl #2: The "Subclinical AKI" Concept

Novel biomarkers (NGAL, KIM-1, TIMP-2×IGFBP7) can detect kidney injury 24-72 hours before creatinine elevation. Consider trending these markers in high-risk patients.

Diagnostic Approach

History and Physical Examination

Volume assessment: CVP, passive leg raise, echocardiography
Medication review: NSAIDs, ACE inhibitors, contrast agents
Signs of systemic disease: Rash, arthritis, neurological symptoms

Laboratory Evaluation

Basic Workup

Complete metabolic panel with phosphorus and magnesium
Urinalysis with microscopy
Urine electrolytes and osmolality
Fractional excretion of sodium (FENa) and urea (FEUrea)

Advanced Testing

Novel biomarkers: NGAL, KIM-1, L-FABP
Tubular stress markers: TIMP-2×IGFBP7 (NephroCheck®)
Complement levels: C3, C4, CH50 if glomerulonephritis suspected

🎯 Clinical Hack #1: The "5-2-1 Rule" for Prerenal AKI

BUN/Cr ratio >20:1
FENa <1% (or FEUrea <35%)
Urine osmolality >500 mOsm/kg
Specific gravity >1.020
Urine sodium <20 mEq/L

Caveat: These indices may be unreliable in elderly patients, those on diuretics, or with CKD.

Management Strategies

Hemodynamic Optimization

Fluid Management

The concept of "fluid responsiveness" has revolutionized critical care nephrology. Static parameters (CVP, PCWP) poorly predict fluid responsiveness.

Dynamic Parameters:

Pulse pressure variation (PPV)
Stroke volume variation (SVV)
Passive leg raise test
Echocardiographic parameters (IVC collapsibility)

💡 Clinical Pearl #3: The "Goldilocks Zone" of Fluid Balance

Aim for euvolemia—both fluid overload and hypovolemia worsen AKI outcomes. Use cumulative fluid balance as a daily metric, targeting neutral balance by day 3 in most patients.

Vasopressor Selection

Norepinephrine: First-line agent, maintains renal perfusion pressure
Vasopressin: Consider early addition, especially in septic shock
Dopamine: Avoid—no renal protective effect and increased arrhythmia risk

Medication Management

Nephrotoxin Avoidance

Contrast agents: Use lowest effective dose, ensure adequate hydration
Aminoglycosides: Consider alternatives, monitor levels
NSAIDs: Discontinue in AKI
ACE inhibitors/ARBs: Hold temporarily in severe AKI

Drug Dosing Adjustments

Utilize estimated GFR from pre-illness baseline, not current creatinine, for chronic medications in acute-on-chronic kidney disease.

Renal Replacement Therapy (RRT)

Indications for RRT

Absolute Indications:

Severe hyperkalemia (K+ >6.5 mEq/L) with ECG changes
Severe metabolic acidosis (pH <7.1)
Uremic complications (pericarditis, encephalopathy, bleeding)
Severe fluid overload unresponsive to diuretics
Certain poisonings (methanol, ethylene glycol, lithium)

Relative Indications:

Progressive azotemia
Oliguria/anuria >24 hours
Fluid overload limiting therapy

🔥 Clinical Pearl #4: Timing Is Everything

The STARRT-AKI trial suggests that for patients without life-threatening complications, watchful waiting may be appropriate. However, don't delay RRT when absolute indications are present.

RRT Modalities

Intermittent Hemodialysis (IHD)

Advantages: Efficient clearance, familiar to staff
Disadvantages: Hemodynamic instability, limited ICU availability

Continuous Renal Replacement Therapy (CRRT)

Advantages: Hemodynamic stability, better fluid control
Disadvantages: Continuous anticoagulation, higher cost, nursing intensive

🎯 Clinical Hack #2: CRRT Prescription Pearls

Dose: 20-25 mL/kg/hr for effluent rate
Anticoagulation: Regional citrate when possible (lower bleeding risk)
Access: Right internal jugular preferred, avoid femoral in obese patients
Filter life: Target >24 hours; frequent clotting suggests inadequate anticoagulation or access issues

Special Populations

Acute-on-Chronic Kidney Disease

Diagnostic Challenges

Baseline creatinine may be unknown
MDRD/CKD-EPI equations unreliable in acute settings
Chronic compensatory mechanisms may mask severity

Management Modifications

Earlier RRT consideration (lower threshold)
Phosphorus management crucial
Bone-mineral disorder considerations
Medication dosing based on chronic, not acute, kidney function

💎 Clinical Pearl #5: The "Nephrology Consultation Sweet Spot"

Involve nephrology early—ideally within 24 hours of AKI recognition. Early consultation improves outcomes and reduces hospital stay.

Cardiorenal Syndrome

Type 1 (Acute Heart Failure → AKI)

Optimize cardiac output
Consider inotropes if low cardiac output
Ultrafiltration may be beneficial

Type 3 (AKI → Acute Heart Failure)

Volume management challenging
Early RRT consideration
Monitor for arrhythmias

Sepsis-Associated AKI

Pathophysiology

Microcirculatory dysfunction
Inflammatory mediator effects
Tubular cell apoptosis

Management

Early source control
Appropriate antibiotics
Hemodynamic support with adequate MAP (>65 mmHg)

Emerging Therapies and Future Directions

Novel Biomarkers

TIMP-2×IGFBP7: FDA-approved for AKI risk stratification
Proenkephalin: Emerging marker for GFR estimation
Urinary [TIMP-2]×[IGFBP7]: Cell cycle arrest biomarkers

Therapeutic Innovations

Alkaline phosphatase: Phase III trials ongoing
Mesenchymal stem cells: Promising preclinical data
Artificial kidney devices: Wearable and implantable options in development

🔮 Clinical Pearl #6: Precision Medicine in AKI

The future lies in phenotype-specific treatments. Genomic markers, metabolomics, and artificial intelligence will likely guide personalized AKI therapy within the next decade.

Recovery and Long-term Outcomes

AKI Recovery Patterns

Complete recovery: Return to baseline kidney function
Partial recovery: Improved but not baseline function
Non-recovery: Progression to CKD or dialysis dependence

Factors Affecting Recovery

Age: Older patients recover less completely
Severity: Higher AKI stages associated with worse outcomes
Duration: Prolonged AKI reduces recovery likelihood
Comorbidities: Diabetes, hypertension worsen prognosis

Long-term Sequelae

Increased CKD risk (HR 2-3×)
Cardiovascular disease
All-cause mortality

Quality Improvement and System-Based Care

AKI Bundles and Protocols

Implement systematic approaches:

Early recognition systems
Standardized management protocols
Multidisciplinary rounds
Discharge planning with nephrology follow-up

📊 Clinical Hack #3: The "AKI Dashboard"

Use electronic health records to create real-time AKI alerts based on:

Creatinine trends
Urine output calculations
High-risk medication exposure
Novel biomarker results

Conclusions and Clinical Takeaways

Early recognition using clinical context and emerging biomarkers improves outcomes
Hemodynamic optimization remains the cornerstone of AKI management
Avoid nephrotoxins and adjust drug dosing appropriately
RRT timing should be individualized based on absolute indications and clinical trajectory
Multidisciplinary care with early nephrology involvement enhances patient outcomes
Long-term follow-up is essential given increased CKD and cardiovascular risks

🎯 Final Clinical Pearl: The "AKI Prevention Mindset"

The best treatment for AKI remains prevention. Maintain high clinical suspicion in at-risk patients, optimize hemodynamics proactively, and avoid unnecessary nephrotoxic exposures.

References

Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1-138.
Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-1423.
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012;380(9843):756-766.
STARRT-AKI Investigators. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med. 2020;383(3):240-251.
Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17(1):R25.
Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019;394(10212):1949-1964.
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. JAMA. 2016;315(20):2190-2199.
Pickkers P, Mehta RL, Murray PT, et al. Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in patients with sepsis-associated acute kidney injury. JAMA. 2018;320(19):1998-2009.
Chawla LS, Bellomo R, Bihorac A, et al. Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol. 2017;13(4):241-257.
Ostermann M, Bellomo R, Burdmann EA, et al. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020;98(2):294-309.

Disclosure: The authors report no conflicts of interest. Word Count: 2,847

Monday, September 1, 2025