Role of C3 and C4 in AKI

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Last updated: February 11, 2025View editorial policy

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From the Guidelines

C3 and C4 do not have a direct role in Acute Kidney Injury (AKI).

Definition and Diagnosis of AKI

AKI is defined as an increase in creatinine by 0.3 mg/dL within 48 hours or an increase in serum creatinine to 1.5 times baseline (within prior 7 days) or urine volume 0.5 mL/kg/hr for 6 hours 1. The diagnosis of AKI is based on changes in serum creatinine and urine output, and it is a complex and multifactorial syndrome with various underlying mechanisms.

Biomarkers for AKI

Traditionally, serum creatinine (sCr) and urine output are used to define AKI, but these markers are limited by delayed changes following kidney injury and have low sensitivity and specificity 1. Several novel biomarkers have been shown to detect AKI earlier and are more sensitive than sCr.

Causes and Risk Factors of AKI

AKI can be caused by prerenal, renal, or postrenal factors, and it is often multifactorial 1. The risk factors for AKI include chronic kidney disease, diabetes, hypertension, and the use of nephrotoxic agents such as contrast media 1.

Management and Prevention of AKI

The management of AKI involves identifying and treating the underlying cause, as well as providing supportive care such as maintaining adequate intravascular volume and using vasopressors 1. Strategies to prevent CI-AKI include minimizing the volume of contrast medium administered, using less-nephrotoxic contrast agents, and providing patient hydration 1.

  • Key points:
    • AKI is a complex and multifactorial syndrome with various underlying mechanisms.
    • C3 and C4 do not have a direct role in AKI.
    • The diagnosis of AKI is based on changes in serum creatinine and urine output.
    • Novel biomarkers can detect AKI earlier and are more sensitive than traditional markers.
    • Identifying and treating the underlying cause of AKI is crucial for management.

From the Research

Role of C3 in AKI

  • C3a/C3 levels in urine have been associated with sepsis and acute kidney injury (AKI) 2
  • Complement activation, including C3, plays a crucial role in the development of AKI in rhabdomyolysis 3
  • C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia-reperfusion AKI and post-injury fibrosis 4
  • Low levels of C3 are superior in predicting poor outcome in ANCA-associated renal vasculitis 5
  • Urinary complement C3 predicts adverse outcomes in patients with AKI after cardiac surgery 6

Role of C4 in AKI

  • Low levels of C4 do not associate with early requirement of kidney replacement therapy or death in ANCA-associated renal vasculitis 5
  • Combining low C3 and/or C4 levels identifies a higher number of cases with poor outcome in ANCA-associated renal vasculitis 5
  • Isolated C4 lowering is observed in a minor fraction of patients with poor outcome, not captured by serum C3 measurements 5

Comparison of C3 and C4 in AKI

  • Low levels of C3 are more predictive of poor outcome than low levels of C4 in ANCA-associated renal vasculitis 5
  • Urinary complement C3, but not C4, is identified as a potential biomarker for predicting adverse outcomes in patients with AKI after cardiac surgery 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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