How to diagnose CKD? Cystatin C, eGFR, and Creatine

The Kidney Disease: Improving Global Outcomes (KDIGO) and the Clinical Practice Guideline for the evaluation and Management of Chronic Kidney Disease focus on assessing, classification, and treating chronic kidney disease (CKD). The main objective of these guidelines is to stop kidney disfunction. However, the CKD classification is complex and depends on an extensive assessment of multiple metabolic and functional markers. As knowledge progresses and evolves, new useful markers like cystatin C become available to classify CKD progression. The use and combinations of eGFR, creatinine, age, microalbumin, and cystatin C allow a reliable way to detect and classify CKD.

Chronic Kidney Disease: KDOQI defines CKD as the abnormalities of kidney structure and function, present for > 3 months, with health implications. Nonetheless, the function and structure may vary, and here is where kidney function markers become crucial to define the staging of this condition.

Staging of CKD

KDOQI guidelines recommend classifying CKD taking into account the following clinical and functional markers:

• eGFR category.
• Albuminuria category
• Clinical cause: This depends on the presence or absence of systemic disease, as well as the location and observation of the presumed pathologic-anatomic findings.

eGFR categories:

Albuminuria categories:

Evaluation of CKD:

The treatment guidelines should be followed after the careful classification of the patient’s kidney function. Furthermore, the evaluation of CKD should consider the classification based on the albuminuria and eGFR category and the time of kidney disfunction. The KDOQI guidelines recommend following CKD treatment if the duration of >3 months of CKD is confirmed. However, if this period cannot be verified or is less than three months, the patient should be reassessed by a clinician to establish CKD or acute kidney disease.

Also, CKD can be a secondary organ failure following a different chronic disease, such as Diabetes Mellitus or Hypertension. The importance of evaluating the cause should consider family history, social and environmental factors, physical examinations, imaging, medications, and previous diseases to provide a diagnosis.

Creatinine and cystatin C: critical control points to diagnose CKD

Another fundamental recommendation from the KDOQI guidelines relies on critical makers such as cystatin C and creatinine.

There are certain instances in which the eGFR is not enough to determine the classification of CKD. Therefore the KDOQI recommends using serum creatinine and a GFR estimating equation for the initial assessment. Regardless of the staging capacity of eGFR and creatinine, these markers cannot measure risk prediction. Also, muscle mass is a crucial determinant of creatinine. As such, creatinine can be variable between patients with low or high muscle mass and should be considered if using the creatinine-dependent eGFR equation.

Cystatin C is an alternative filtration marker with a more robust and linear relationship to risk prediction than creatinine. Cystatin C levels are kept under normal ranges when the kidneys are functioning correctly. Literature suggests that cystatin C improves the role of eGFR by determining the risk classification of death, cardiovascular disease, and end-stage renal disease.

non-GFR determinants of serum creatinine:

• Muscle mass
• Diet
• Physical activity

non-GFR determinants of cystatin C

• Obesity
• Inflammation
• Diabetes 

Cystatin C

The significance of determinants like race, age, creatinine levels, and gender are crucial to determine eGFR. However, there are critical circumstances where cystatin C could be used in addition to eGFR.

• If the patient has undergone biochemical and clinical assessment and kidney function was inconclusive.
• If the patient has overweight, an excessive muscle mass (as in bodybuilders or shallow muscle mass. The elderly population can benefit from cystatin C measurement as well.

Finally, recent guidelines suggest using cystatin C and eGFR to determine CKD staging when microalbuminuria cannot be measured. Regardless of the importance of creatinine levels and eGFR, cystatin C should be considered an alternative if the patient has a muscle amount above or under the normal ranges. Moreover, age is a critical determinant of creatinine and eGFR, as well as cystatin C. This factor is probably due to the loss of muscle mass or cell mass seen in the elderly population. 

The KDIGO and KDOQI guidelines are aware of patient diversity and how a simple biochemical marker is not enough to classify kidney disease. Therefore, cystatin C is a valuable tool to determine the filtration rate in those patients who are difficult to detect and diagnose. In addition, creatinine levels can vary widely depending on the type of diet, exercise, and patient race. Using and considering all the filtration markers, the risk, classification, and progression of kidney function can be tracked and treated. – Ana Paola Rodríguez Arciniega, MS.

References

Shlipak, Michael G et al. “Cystatin C versus creatinine in determining risk based on kidney function.” The New England journal of medicine vol. 369,10 (2013): 932-43. doi:10.1056/NEJMoa1214234

Eknoyan, Garabed, et al. “KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.” Kidney Int 3.1 (2013): 5-14.

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