Can cystatin C (Cystatin C) levels reflect anything other than impaired renal function?

From the Guidelines

Cystatin C levels can reflect not only impaired renal function but also other health conditions, including cardiovascular disease, systemic inflammation, certain cancers, thyroid dysfunction, and age-related changes. The most recent and highest quality study, 1, recommends the use of cystatin C for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate. Some key points to consider when interpreting cystatin C levels include:

• Elevated cystatin C may be associated with cardiovascular disease, serving as a predictor of heart failure and stroke risk independent of kidney function 1
• Cystatin C can reflect systemic inflammation, as levels increase during inflammatory states
• Cystatin C may also be elevated in certain cancers, including melanoma, colorectal, and lung cancer, where it can indicate tumor progression
• Thyroid dysfunction affects cystatin C, with hypothyroidism decreasing levels and hyperthyroidism increasing them
• Glucocorticoid use, obesity, and smoking can also raise cystatin C levels
• Age-related changes occur naturally, with levels typically increasing as people get older It is essential to consider these additional associations when interpreting cystatin C results, especially in patients with comorbidities or those taking medications that might influence cystatin C production 1. In clinical practice, cystatin C can be a valuable marker for kidney function, but its interpretation should be done in the context of the patient's overall health and medical history, taking into account the potential effects of non-renal factors on cystatin C levels 1.

From the Research

Cystatin C Levels and Their Reflection of Impaired Renal Function

• Cystatin C is a marker of renal function and a major cardiovascular risk factor 2, 3, 4, 5, 6
• Studies have shown that cystatin C levels can reflect not only impaired renal function but also other factors such as:
  • Inflammatory status and oxidative stress, although one study found no correlation between cystatin C and inflammatory markers in non-diabetic patients with chronic kidney disease 2
  • Cardiovascular risk factors, including cardiovascular disease and mortality 4, 5, 6
  • Vascular dysfunction, including the renal resistive index 3
• Cystatin C has been found to be a stronger predictor of renal outcome and cardiovascular events than creatinine level 3, 4, 6
• Elevated cystatin C concentrations have been associated with a higher risk of progressing to chronic kidney disease, even in individuals without chronic kidney disease 4

Non-Renal Influences on Cystatin C Concentrations

• Some studies have suggested that cystatin C concentrations may be influenced by non-renal factors, such as:
  • Age, male sex, increased height and weight, smoking, and higher C-reactive protein levels 6
  • Local cystatin C deficiency in atherosclerotic and aneurismal lesions, which may suggest a protective role of cystatin C in the vessel wall 5
• However, other studies have found that cystatin C is closely related to the degree of renal dysfunction, and that non-renal factors do not significantly influence cystatin C levels 2, 3

Association with Cardiovascular Disease

• Cystatin C has been found to be associated with an increased risk of cardiovascular disease, including heart failure, stroke, and myocardial infarction 4, 5
• The association between cystatin C and cardiovascular disease may be due to the fact that cystatin C reflects early kidney dysfunction, which is a risk factor for cardiovascular disease 4, 6