Creatinine Levels and Pseudohypercreatininemia

Creatinine levels are considered to be the gold standard to define kidney functioning in patients. Elevated creatinine concentrations often indicate acute renal injury, and renal biopsies are the most preferred diagnostic methods in this situation. Creatinine may be measured using the Jaffe method and enzymatic methods. The latter has high specificity and is used by many medical institutions.

Paraproteins can interfere in the determination of various clinically important analytes in an unpredictable manner, affecting different methodologies. Interferences of mild to moderate degree have been reported affecting the measurement of serum creatinine. Pseudohypercreatininemia caused by immunoglobulin (Ig)M can be misleading, but there are no reports of pseudohypercreatininemia.

Case Study

A case study in BMC Nephrology reports a rare case of a woman with falsely elevated creatinine concentration with the presence of abnormal proteins. Pseudohypercreatininemia should be considered as a differential diagnosis to prevent invasive procedures in patients.

A 54-year-old woman underwent surgery for descending aortic dissection. At admission, she had developed another aortic dissection in the descending aorta and underwent graft replacement. She had multiple aortic dissections at a young age but had no findings or family history of Marfan syndrome or Ehlers–Danlos syndrome. Because of severe intraoperative bleeding, she was transfused with 10 units of red blood cells, 4 units of fresh-frozen plasma, and 10 units of platelets, and her creatinine concentration was approximately 1 mg/dl. Nine days postoperatively, her creatinine concentration increased from 1 mg/dl to 5.78 mg/dl. Azotemia and hyperkalemia were absent, and physical examination findings were unremarkable.

The case study found that:

• Cystatin C concentration was 1.56 mg/l (normal range, 0.56–0.8 mg/l) and pseudohypercreatininemia was suspected.
• Testing with different reagents showed a creatinine concentration of 0.84 mg/dl. Immunoglobulin (Ig)G was markedly elevated, and creatinine and IgG fluctuated in parallel, suggesting the cause of the pseudohypercreatininemia.
• IgG4 was also elevated at 844 mg/dl. Immunosuppressive steroid therapy effectively decreased the IgG concentration and resolved the pseudohypercreatininemia.

Researchers concluded that “In cases of elevated creatinine concentration with the presence of abnormal proteins, pseudohypercreatininemia should be considered. We report a rare case of pseudohypercreatininemia caused by polyclonal IgG.”

Reference: Tasaki, A., Fukuda, M., Ikeda, Y. et al. Pseudohypercreatininemia after surgery for aortic dissection: a case report. BMC Nephrol 24, 220 (2023). https://doi.org/10.1186/s12882-023-03275-2