What differentiates Acute Kidney Injury (AKI) from Chronic Kidney Disease (CKD) progression?

From the Guidelines

Acute Kidney Injury on Chronic Kidney Disease (AKI on CKD) and CKD progression are distinct clinical entities that require different management approaches, with AKI on CKD being an abrupt decline in kidney function superimposed on pre-existing chronic kidney disease, and CKD progression representing a gradual, often irreversible decline in kidney function over months to years. The differentiation between AKI on CKD and CKD progression is crucial for appropriate management and treatment. AKI on CKD is characterized by a sudden increase in serum creatinine (typically ≥0.3 mg/dL within 48 hours or ≥50% increase from baseline within 7 days) or decreased urine output, and is often reversible with proper intervention 1. In contrast, CKD progression is a gradual decline in kidney function, typically showing a steady increase in creatinine and decline in estimated glomerular filtration rate (eGFR) over months to years, and is managed by controlling the underlying disease, strict blood pressure control, and use of medications such as ACE inhibitors or ARBs 1.

Some key points to consider in differentiating between AKI on CKD and CKD progression include:

• Temporality: AKI on CKD is an acute event, while CKD progression is a chronic process
• Reversibility: AKI on CKD is often reversible with proper intervention, while CKD progression is typically managed by slowing rather than reversing the decline
• Underlying cause: AKI on CKD is often triggered by specific events such as dehydration, nephrotoxic medications, or infection, while CKD progression results from ongoing damage due to underlying conditions such as diabetes, hypertension, or glomerulonephritis
• Management: AKI on CKD requires identifying and treating the acute cause, temporarily adjusting medications, maintaining hydration, and monitoring for recovery, while CKD progression requires controlling the underlying disease, strict blood pressure control, and use of medications such as ACE inhibitors or ARBs.

It is also important to note that the use of certain medications, such as ACE inhibitors or ARBs, should not be discontinued for minor increases in serum creatinine (<30%), in the absence of volume depletion, as this can provide benefit in slowing kidney disease progression 1. Additionally, the maximally tolerated doses of these medications should be used, rather than very low doses that do not provide benefit.

From the Research

Differentiation between AKI on CKD vs CKD Progression

• AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD 2.
• The distinction between AKI and CKD may be artificial, and consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages 2.
• AKI is a risk factor for CKD development and progression to end stage renal disease (ESRD) 3.
• Acute kidney disease (AKD) is defined as the post-AKI status of acute or subacute kidney damage/dysfunction manifested by persistence of AKI beyond 7 to 90 days after the initial AKI diagnosis 4.

Key Factors in Differentiation

• Severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes 2.
• Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD 2.
• Maladaptive repair is an interplay of cell death, endothelial dysfunction, tubular epithelial cell senescence, inflammatory processes and more-terminating in fibrosis 3.

Clinical Implications

• Patients with AKI should be reviewed to ascertain the cause of AKI and the severity of the injury should be staged 5.
• Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function 2.
• Interventions on fluid management, nephrotoxic exposure, and follow-up care hold promise to ameliorate the burden of AKD and its complications 4.
• The frequent assessment of urinary biochemistry and microscopy can be useful in evaluating the likelihood of AKI reversibility 6.