Serum Creatinine and eGFR

Serum creatinine has long been used to estimate GFR, but it is an indirect and unreliable marker until GFR has declined substantially. More accurate estimated GFR (eGFR) formulas have been developed based on creatinine, age, sex and race. However, eGFR also has limitations as a late-stage biomarker. Rising or abnormal creatinine may not occur until 40-50% of kidney function is already lost. Novel biomarkers could provide insight into kidney health even before eGFR declines.

Neutrophil Gelatinase-Associated Lipocalin

One highly promising biomarker is Neutrophil Gelatinase-Associated Lipocalin (NGAL). NGAL is a protein produced by the kidney tubules soon after injury occurs. Research has found NGAL levels rise within two hours of kidney damage, making it a very early marker. Studies show NGAL may predict acute kidney injury (AKI) 12-24 hours before rises in creatinine. It also correlates with CKD progression risk. Hospitals have started using a rapid NGAL lab test to help diagnose AKI sooner for better outcomes.

Kidney Injury Molecule-1

Another Renal Biomarkers showing promise is Kidney Injury Molecule-1 (KIM-1). Like NGAL, KIM-1 is produced by damaged kidney tubule cells. It may help identify and assess acute and chronic tubular injury. Research found elevated urinary KIM-1 predicted GFR decline in CKD patients, making it a potential risk prognosticator. KIM-1 may provide insight on Cystinosis, a rare kidney disease, and drug-induced kidney tubular toxicity as well.

Cystatin C

Whereas creatinine depends on muscle mass, Cystatin C is less affected by non-kidney factors like age, sex, weight. It is freely filtered by kidneys and reabsorbed by tubules. Some studies found Cystatin C detected GFR loss earlier than creatinine or eGFR. Combining Cystatin C with creatinine could provide a more sensitive picture of early kidney function changes. Ongoing research aims to refine Cystatin C’s clinical role in CKD screening, risk prediction, and monitoring transitional stages between acute and chronic kidney diseases.

Fibrosis Biomarkers

Progressive scarring or fibrosis of the kidney tissues is a major driver of CKD progression. Development of robust fibrosis biomarkers has the potential to revolutionize early detection strategies and anti-fibrotic treatment management. Promising candidates include pro-collagen III N-terminal propeptide (P3NP) which reflects collagen synthesis, and matrix metalloproteinases which indicate collagen breakdown. If validated in large studies, fibrosis markers could open doors to earlier, personalized anti-fibrotic interventions in CKD.

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