What are alternative tests for assessing kidney health beyond Glomerular Filtration Rate (GFR)?

From the Guidelines

A comprehensive assessment of kidney health should include a combination of tests, such as the urine albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), serum creatinine, cystatin C, and a complete urinalysis, in addition to GFR. These tests provide a more accurate evaluation of kidney function and damage, allowing for earlier intervention and potentially improving outcomes. The UACR is particularly useful as it detects small amounts of protein leaking into the urine, often before GFR changes become apparent, with a normal UACR being less than 30 mg/g, and values between 30-300 mg/g indicating microalbuminuria and over 300 mg/g suggesting macroalbuminuria 1. Other beneficial tests include serum cystatin C, which represents a more accurate estimation of GFR and is less influenced by age and diabetes than is serum creatinine, with decreased GFR associated with higher levels of cystatin C 1. A complete urinalysis that examines for blood, protein, and sediment, as well as kidney ultrasound, which provides structural information, should also be included in the assessment. Regular monitoring with this comprehensive approach allows for earlier intervention in kidney disease, potentially slowing progression and improving outcomes. Key points to consider when assessing kidney health include:

• The importance of assessing both kidney function and damage
• The use of UACR to detect small amounts of protein leaking into the urine
• The benefits of including serum cystatin C in the assessment
• The need for regular monitoring and a comprehensive approach to kidney health assessment.

From the Research

Alternative Tests for Assessing Kidney Health

• Cystatin C has been shown to be a reliable and accurate marker of kidney function across diverse populations 2, 3, 4, 5
• The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin C to confirm the diagnosis of chronic kidney disease (CKD) determined by creatinine-based estimated glomerular filtration rate (eGFR) and to estimate kidney function when accurate eGFR estimates are needed for clinical decision-making 2
• Cystatin C improves sensitivity and specificity of chronic kidney disease diagnosis, improves detection of harmful acute and chronic changes in kidney function, improves precision of treatment eligibility and safety, and may reduce healthcare inequalities 3
• Proteinuria adds value to GFR estimation 4
• The Chronic Renal Insufficiency Cohort (CRIC) study has devised an equation combining serum creatinine and cystatin C in longitudinal modeling of kidney function 4
• The CKD-EPIcreat-cys equation combining both markers demonstrates improved accuracy in GFR estimation, especially for individuals with eGFR values of 45-59 mL/min/1.73 m2 5
• Radiolabeled-tracer plasma or urinary clearance methods are safe, simple, accurate, and reproducible for GFR measurements 6

Advantages of Cystatin C

• Cystatin C is unaffected by muscle mass and shows stronger associations with cardiovascular disease and mortality than creatinine 5
• Cystatin C-based estimates of GFR outperform creatinine-based estimates in predicting clinical outcomes and identifying patients at higher risk, particularly in elderly and non-white ethnic groups 5
• Cystatin C offers advantages over creatinine as a marker of kidney function, as it is not influenced by non-kidney factors and provides more accurate estimation of GFR 5

Limitations of Current Tests

• Exogenous compounds like inulin help measure GFR, but endogenous substances (like creatinine) are more convenient, although exhibiting greater variability 4
• Current GFR estimation methods have limitations, and are useful for populations they have been tested in 4
• Prediction equations based on serum creatinine have limitations, especially in the normal or near-normal GFR range, kidney transplant recipients, and pediatric populations 6