What type of kidney injury increases the risk of developing diabetic ketoacidosis (DKA) in patients with diabetes?

Acute Kidney Injury (AKI) and Diabetic Ketoacidosis (DKA)

Acute kidney injury (AKI) is the primary type of kidney injury that increases the risk of developing diabetic ketoacidosis (DKA) in patients with diabetes, with preexisting chronic kidney disease (CKD) being a significant contributing factor. 1

Relationship Between AKI and DKA

• AKI is diagnosed by a 50% or greater sustained increase in serum creatinine over a short period of time, which is reflected as a rapid decrease in estimated glomerular filtration rate (eGFR) 2
• People with diabetes are inherently at higher risk of developing AKI compared to those without diabetes 2
• AKI occurs in approximately 55% of patients hospitalized with DKA, making it a common complication 1
• The relationship between AKI and DKA is bidirectional - AKI can both precipitate DKA and occur as a complication of DKA 1, 3

Risk Factors for AKI in Diabetic Patients

• Preexisting chronic kidney disease (CKD) significantly increases the risk of AKI in patients with diabetes 2
• Use of medications that alter renal blood flow and intrarenal hemodynamics, including:
  • Diuretics 2
  • ACE inhibitors and angiotensin receptor blockers (ARBs) 2
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 2
• Volume depletion, which is common in the setting of hyperglycemia and osmotic diuresis 2
• Advanced age, elevated blood glucose, increased serum uric acid, elevated white blood cell count, decreased serum pH, hypoalbuminemia, and altered consciousness are specific risk factors for AKI in DKA patients 1

Pathophysiology of AKI Leading to DKA

• AKI causes metabolic acidosis, which can worsen insulin resistance and impair insulin secretion 4
• In CKD and AKI, uremic toxins accumulate, leading to increased insulin resistance and reduced peripheral utilization of insulin 4
• AKI can lead to electrolyte abnormalities (particularly hyperkalemia) that further complicate glucose metabolism 2
• Volume depletion from AKI can trigger stress hormone release (catecholamines, cortisol), which antagonize insulin action and promote ketogenesis 1, 4

Specific AKI Patterns Associated with DKA

• Oliguric AKI (decreased urine output <0.5 ml/kg/hr) is particularly concerning as it indicates significant kidney dysfunction and is associated with worse outcomes in DKA 3
• Moderate to severe AKI (stages 2-3) develops in approximately 15.5% of DKA episodes and is associated with poorer outcomes 5
• Rhabdomyolysis-induced AKI can occur during the course of DKA and further worsen kidney function 3

Clinical Implications and Management

• Early recognition and treatment of AKI during DKA may improve prognosis 3
• Patients with DKA who develop AKI show more than a two-fold decline in eGFR within 1 year after discharge compared to non-AKI DKA patients 1
• AKI is an independent risk factor for poor long-term renal outcomes and mortality in DKA patients 1
• In severe cases, renal replacement therapy (continuous venovenous hemofiltration) may be required to correct metabolic abnormalities and improve outcomes 6, 3

Special Considerations in End-Stage Renal Disease

• DKA presents differently in hemodialysis patients due to the absence of glycosuria and osmotic diuresis 4
• Anuric patients may be somewhat protected from dehydration and shock but remain susceptible to hyperkalemia and metabolic acidosis 4
• Volume loss can still occur in these patients due to decreased oral intake or increased insensible water losses related to tachypnea and fever 4

Early identification of AKI in diabetic patients is crucial for preventing the development of DKA and improving outcomes. Regular monitoring of renal function, especially in high-risk patients, is essential for timely intervention.