AKI on CKD: Definition and Quantification
AKI on CKD refers to acute kidney injury occurring in patients with pre-existing chronic kidney disease, and it is quantified using the same KDIGO criteria as regular AKI (serum creatinine rise ≥0.3 mg/dL within 48 hours OR ≥50% increase within 7 days OR urine output <0.5 mL/kg/h for ≥6 hours), with the critical distinction that baseline kidney function is already impaired. 1
What is AKI on CKD?
AKI on CKD represents the superimposition of acute kidney injury on pre-existing chronic kidney disease, creating a particularly high-risk clinical scenario. 1 This condition is characterized by:
- An abrupt decline in kidney function (meeting KDIGO AKI criteria) occurring in a patient who already has CKD (GFR <60 mL/min/1.73 m² or markers of kidney damage for >3 months). 1
- Heightened injury severity and suppressed repair mechanisms compared to AKI in patients with normal baseline kidney function. 2
- Significantly worse outcomes, with one study showing AKD on CKD versus CKD alone had mortality of 47.0% vs. 19.3% and an odds ratio of 16.8 for incident CKD progression. 1
The pathophysiology underlying this heightened vulnerability includes chronic inflammation, vascular dysfunction, mitochondrial dysfunction, oxidative stress, aberrant autophagy, and activation of maladaptive signaling pathways (TGF-β, p53, HIF) that make the kidney more susceptible to acute insults and less capable of recovery. 2
How to Quantify AKI on CKD
Step 1: Establish Baseline Kidney Function
Use the patient's most recent stable creatinine value to define their baseline CKD status. 3
- Known creatinine values are superior to imputation methods, as back-calculation from an estimated GFR of 75 mL/min/1.73 m² may overestimate AKI incidence in populations with high CKD prevalence. 3
- Document the patient's CKD stage using KDIGO CGA classification (Cause, GFR category G1-G5, Albuminuria category A1-A3). 1
Step 2: Apply Standard KDIGO AKI Criteria
AKI on CKD is diagnosed when ANY of the following occur relative to the CKD baseline: 1, 3
- Serum creatinine increase ≥0.3 mg/dL (≥26 μmol/L) within 48 hours, OR
- Serum creatinine increase ≥50% from baseline within 7 days, OR
- Urine output <0.5 mL/kg/h for ≥6 hours
Step 3: Stage the AKI Component
Apply KDIGO AKI staging based on the magnitude of change from the CKD baseline: 1, 3
- Stage 1: Creatinine 1.5-1.9× baseline OR increase ≥0.3 mg/dL OR urine output <0.5 mL/kg/h for 6-12 hours
- Stage 2: Creatinine 2.0-2.9× baseline OR urine output <0.5 mL/kg/h for ≥12 hours
- Stage 3: Creatinine ≥3.0× baseline OR increase to ≥4.0 mg/dL OR urine output <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours OR initiation of kidney replacement therapy
Step 4: Consider the Acute Kidney Disease (AKD) Framework
If kidney dysfunction persists beyond 7 days but less than 90 days, the patient has AKD on CKD. 1, 3
- AKD is defined as: AKI, OR GFR <60 mL/min/1.73 m², OR markers of kidney damage, OR decrease in GFR ≥35%, OR increase in serum creatinine >50% for ≤3 months. 1
- AKI is a subset of AKD, such that AKD can occur with or without meeting formal AKI criteria. 1
- After 3 months, if dysfunction persists, the patient is described as having CKD with a history of AKD, at increased risk for CKD progression. 1
KDIGO Definitions for AKI on CKD
Yes, KDIGO provides the same standardized definitions for AKI regardless of whether it occurs in patients with or without pre-existing CKD. 1 The 2021 KDIGO Consensus Conference specifically addressed the continuum of AKI, AKD, and CKD, harmonizing definitions across this spectrum. 1
Key KDIGO framework elements: 1
- 0-7 days of dysfunction = AKI
- 7-90 days of dysfunction = AKD (which includes persistent AKI)
- >90 days of dysfunction = CKD
The KDIGO consensus explicitly recognizes that AKI and CKD are interconnected syndromes that can coexist, with AKI occurring in patients with CKD representing a particularly high-risk phenotype. 1
Critical Clinical Considerations
Outcome Implications
AKI on CKD carries dramatically worse prognosis than either condition alone: 1
- Mortality: Adjusted HR 2.51 for AKD post-AKI versus no AKD 1
- CKD progression: OR 16.8 for AKD on CKD versus CKD alone in cardiac surgery patients 1
- Long-term kidney failure risk: Substantially elevated even after apparent recovery 1
Common Pitfalls to Avoid
Do not rely solely on serum creatinine without considering urine output criteria, as this may miss cases of AKI. 3 However, recognize that urine output criteria are unreliable in patients with cirrhosis and ascites, who may be oliguric with avid sodium retention yet maintain relatively normal GFR. 3
Do not assume that small creatinine increases are clinically insignificant in CKD patients—even a 0.3 mg/dL rise is independently associated with approximately fourfold increase in hospital mortality. 3
Serum creatinine has inherent limitations in CKD populations, being affected by decreased muscle mass, increased tubular secretion, volume expansion, and assay interference from elevated bilirubin. 3
Consider measured GFR rather than estimated GFR when kidney function is changing rapidly during the acute phase. 4
Management Priorities for AKI on CKD
Immediate interventions differ from chronic CKD management: 5, 4
- Discontinue all nephrotoxic agents immediately 5, 4
- Ensure adequate volume status and perfusion pressure, particularly critical in prerenal states and cardiorenal syndrome 5, 4
- Monitor serum creatinine and urine output closely (multiple times daily during acute phase) 5, 4
- Adjust medication dosing based on current kidney function (high priority intervention) 5, 4
- Consider kidney biopsy for unresolving AKI/AKD when etiology remains unclear 5, 4
As GFR stabilizes after AKI, transition from AKI-based staging to GFR-based CKD categories and implement long-term CKD management strategies including ACE inhibitor or ARB therapy for patients with hypertension and proteinuria (but avoid dual RAAS blockade due to hyperkalemia and AKI risk). 5, 4