Clinical Pearls & Morning Reports

By Carla Rothaus

Published June 1, 2022


Are there advantages to using the serum cystatin C level to estimate GFR?

Kidney disease may be classified according to its underlying cause and by the degree of impairment of glomerular filtration rate (GFR) and the level of albuminuria because of the importance of each of these factors in prognosis and treatment. Read the NEJM Review Article here.

Clinical Pearls

Q: What are some of the causes of increased albuminuria?

A: Increased albuminuria, reflecting impairment of the permselective barrier function of the glomerular capillary wall to macromolecules, is a marker of kidney damage. Increased albuminuria is seen in early stages of kidney disease due to diabetes, other glomerular diseases, or hypertension, and in later stages of almost all causes of kidney disease. Numerous pathologic processes, such as inflammation, infiltration, or fibrosis, can cause albuminuria.

Q: Is the global burden of kidney disease changing?

A: The aging population and the obesity epidemic are leading to a growing burden of both acute kidney disease and chronic kidney disease (CKD) globally. The annual number of deaths from kidney failure is 1.2 million, with an additional 1.4 million deaths due to cardiovascular disease (CVD) attributed to CKD; thus, 4.6% of all deaths are due to CKD (making it the 12th leading cause of death). These results underscore the need for detection, evaluation, and treatment of even early stages of kidney disease to slow progression and prevent complications.

Morning Report Questions

Q: Are there advantages to using the serum cystatin C level to estimate GFR?

A: The true GFR cannot be measured directly in humans. GFR can be assessed from the clearance or plasma (or serum) concentrations of filtration markers (low-molecular-weight substances that are eliminated primarily by glomerular filtration). For evaluation of the GFR, current guidelines recommend using GFR-estimating equations, with GFR estimated on the basis of the serum creatinine level (eGFRcr) as the initial test. Recent recommendations encourage the use of serum cystatin C levels in estimating the GFR because cystatin C is not affected by race or world region and appears to enable a more accurate eGFR determination. Assays for cystatin C are more expensive than those for creatinine, and use of cystatin C is currently limited by reimbursement policies, but there are opportunities to reduce its costs and advocate for changes in policy. As compared with creatinine, cystatin C is less affected by age, sex, race, and world region but is more affected by obesity, smoking, inflammation, and alterations in thyroid and glucocorticoid hormones. A lower eGFRcys is more strongly associated with CVD than is a lower eGFRcr, which provides additional justification for more widespread use of cystatin C.

Q: Describe some of the ways in which a decreased GFR and increased albuminuria are used for risk prediction.

A: The GFR and level of albuminuria are used in risk-prediction instruments such as equations to guide clinical decision making. For example, the Kidney Failure Risk Equation uses the GFR, albumin-to-creatinine ratio, age, and sex to predict the 2-year and 5-year risks of kidney failure with replacement therapy for patients with a GFR of less than 60 ml per minute per 1.73 m2, and its routine use is recommended by current guidelines to guide evaluation and treatment. A higher predicted risk can be used to prioritize referral for a consultation with a nephrologist, multidisciplinary CKD care, or planning for kidney-replacement therapy. The GFR and level of albuminuria can also be incorporated into existing CVD risk prediction instruments to modify CVD risk predictions. More frequent use of these and other instruments holds promise for improving a broad spectrum of clinical outcomes across the full range of GFR and albuminuria values.

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