Cystatin C As a GFR Estimation Marker in Acute and Chronic Illness: A Systematic Review

Rationale & Objective: Creatinine-based GFR estimating (eGFRcr) equations may be inaccurate in populations with acute or chronic illness. The accuracy of GFR equations that use cystatin C (eGFRcys) or creatinine-cystatin C (eGFRcr-cys) is not well studied in these populations.

Study Design: A systematic review of original articles identified from PubMed and expert sources. Two reviewers screened articles independently and identified those meeting inclusion criteria.

Setting & Study Populations: Adults and children with acute or chronic illness.

Selection Criteria For Studies: Studies published since 2011 that compared performance of eGFRcr, eGFRcys, and eGFRcr-cys relative to measured GFR (mGFR), used standardized assays for creatinine or cystatin C, and used eGFR equations developed using such assays. Studies of ambulatory clinical populations or research studies in populations with only CKD, kidney transplant recipients, only diabetes, kidney donor candidates, and community-based cohorts were excluded.

Data Extraction: Data extracted from full text.

Analytical Approach: Bias and percentages of estimates within 30% of mGFR (P) of eGFR compared with mGFR were evaluated.

Results: Of the 179 citations, 26 studies met the inclusion criteria: 24 in adults and 2 in children in clinical populations with cancer (n=5), HIV (n=5), cirrhosis (n=3), liver transplant (n=3), heart failure (n=2), neuromuscular diseases (n=1) critical illness (n=5), and obesity (n=2). In general, eGFRcr-cys had greater accuracy than eGFRcr or eGFRcys equations among study populations with cancer, HIV, and obesity, but did not perform consistently better in cirrhosis, liver transplant, heart failure, neuromuscular disease, and critical illness.

Limitations: Participants were selected because of concern for inaccurate eGFRcr, which may bias results. Most studies had small sample sizes, limiting generalizability.

Conclusions: eGFRcr-cys improves GFR estimation in populations with a variety of acute and chronic illnesses, providing indications for cystatin C measurement. Performance was poor in many studies, suggesting the need for more frequent mGFR.

Plain-language Summary: Kidney function, specifically glomerular filtration rate (GFR), estimated using creatinine (eGFRcr) is often inaccurate in people with acute and chronic illness. The accuracy of estimates using cystatin C alone (eGFRcys) or together with creatinine (eGFRcr-cys) is not well studied in these populations. We conducted a systematic review to address the knowledge gap. Of the 179 papers reviewed, we identified 26 studies in clinical populations with cancer (n=5); HIV (n=5); cirrhosis (n=3); liver transplant (n=3); heart failure (n=2); neuromuscular disease (n=1); critical illness (n=5); and obesity (n=2). In general, eGFRcr-cys improved the GFR estimation in HIV, cancer, and obesity, providing indications for cystatin C measurement. Performance was poor in many studies, suggesting the need for more frequent measured GFR.