What is subacute kidney dysfunction and its relationship to acute kidney injury (AKI) and chronic kidney disease (CKD)?

Subacute Kidney Dysfunction: The Bridge Between AKI and CKD

Subacute kidney dysfunction, formally termed acute kidney disease (AKD), represents the critical period between acute kidney injury (AKI) and chronic kidney disease (CKD), lasting from 7 to 90 days after an initial kidney insult, and requires specific monitoring and management to prevent progression to CKD. 1

Definition and Conceptual Framework

AKD is defined as abnormalities in kidney structure or function that persist for 7-90 days after an exposure that caused AKI or the new onset of kidney damage or decreased function. It serves as a crucial bridge in the continuum between AKI and CKD:

• AKI: Abrupt decrease in kidney function occurring over 7 days or less 1
• AKD: Subacute damage and/or loss of kidney function persisting 7-90 days 1
• CKD: Abnormalities in kidney structure or function persisting >3 months 2

AKD can occur in two main patterns:

1. AKD with preceding AKI: When AKI persists beyond 7 days
2. AKD without AKI: When kidney dysfunction develops more gradually than AKI criteria but within 90 days 1

Clinical Significance and Outcomes

AKD represents a critical window for intervention to prevent CKD development. Multiple studies demonstrate that AKD significantly increases risk for:

• Mortality: Patients with AKD have up to 63 times higher risk of death compared to those without kidney dysfunction 1
• CKD development: 1.5-16.8 times higher risk of developing CKD 1
• Cardiovascular events: Significantly increased risk compared to patients without AKD 3

The risk is particularly pronounced in:

• Elderly patients
• Those with pre-existing comorbidities (diabetes, hypertension)
• Patients who experienced severe or multiple AKI episodes 3

Pathophysiological Mechanisms

The transition from AKI to AKD to CKD involves several interconnected pathways:

• Failed repair mechanisms: Incomplete recovery of tubular epithelial cells
• Cell cycle arrest: Tubular cells enter a senescent state
• Chronic inflammation: Persistent inflammatory response after initial injury
• Fibrosis development: Progressive replacement of functional tissue with fibrotic tissue
• Renin-angiotensin system activation: Promoting hypertension and further kidney damage 3, 4

Diagnosis and Monitoring

Diagnosis of AKD requires:

1. Functional criteria:

   • GFR <60 mL/min/1.73m² for <3 months
   • Decrease in GFR by ≥35% for <3 months
   • Increase in serum creatinine by ≥50% for <3 months 1

2. Structural criteria:

   • Kidney damage for <3 months (albuminuria, urinary sediment abnormalities, electrolyte disorders, histological abnormalities, imaging abnormalities) 1

Monitoring recommendations:

• Measure serum creatinine and electrolytes at least every 48 hours during active AKD 2
• Monitor fluid balance daily in hospitalized patients 2
• Schedule follow-up at 3 months after AKI/AKD episode to assess for CKD development 2

Management Approach

Management of AKD should focus on:

1. Prevention of repeated kidney insults:

   • Avoid nephrotoxic medications when possible 1, 2
   • Ensure optimal volume status (euvolemia) 2
   • Use balanced crystalloid solutions rather than 0.9% saline for fluid resuscitation 2

2. Medication management:

   • Review and adjust medication dosing based on current kidney function 1
   • Particular caution with NSAIDs, aminoglycosides, and combinations of diuretics with ACE inhibitors/ARBs 2

3. Blood pressure control:

   • Target BP ≤140/90 mmHg for patients with albuminuria <30 mg/24h
   • Target BP ≤130/80 mmHg for patients with albuminuria ≥30 mg/24h 2

4. Consider nephrology consultation for:

   • Worsening kidney function despite initial management
   • AKD not resolved after 48 hours of appropriate therapy
   • Need for renal replacement therapy
   • Diagnostic uncertainty about cause 2

Common Pitfalls in AKD Management

1. Failure to recognize AKD: Many clinicians focus only on AKI or CKD, missing the critical AKD period
2. Inadequate follow-up: Not scheduling appropriate follow-up after AKI episodes
3. Premature medication resumption: Restarting nephrotoxic medications too soon after AKI
4. Relying solely on serum creatinine: Not calculating eGFR or measuring albuminuria
5. Overlooking recurrent injury risk: Not implementing preventive strategies against repeated kidney insults 2

Conclusion

The recognition of AKD as a distinct entity in the continuum between AKI and CKD provides a crucial opportunity for intervention to prevent CKD development. Proper identification, monitoring, and management of patients with AKD can significantly improve long-term outcomes and reduce the burden of chronic kidney disease.