- Biomarkers in kidney injury are measurable biological indicators used to detect, assess, and monitor damage to the kidneys, often before significant loss of renal function becomes clinically apparent. These biomarkers, primarily found in blood or urine, reflect molecular, cellular, or physiological changes associated with acute kidney injury (AKI) or chronic kidney disease (CKD). AKI is a rapid decline in kidney function caused by factors like ischemia, nephrotoxins, or sepsis, while CKD involves progressive renal damage from conditions such as diabetes or hypertension.
- Biomarkers enhance early diagnosis, guide prognosis, predict treatment response, and monitor disease progression, addressing limitations of traditional markers like serum creatinine and urine output, which lack sensitivity and specificity. The development of kidney injury biomarkers leverages advanced omics technologies and requires rigorous validation to ensure clinical reliability across diverse patient populations.
- In AKI, novel blood and urine biomarkers have revolutionized early detection, as serum creatinine rises only after significant renal damage. Neutrophil gelatinase-associated lipocalin (NGAL), a protein upregulated in tubular injury, is detectable in blood and urine within hours of AKI onset, making it a sensitive diagnostic biomarker for conditions like post-cardiac surgery AKI or contrast-induced nephropathy. Kidney injury molecule-1 (KIM-1), a transmembrane protein expressed in proximal tubules after injury, is a urine biomarker specific for tubular damage. Other urinary biomarkers include interleukin-18 (IL-18), which reflects inflammation, and liver-type fatty acid-binding protein (L-FABP), which indicates hypoxic stress. Blood-based biomarkers like cystatin C, a marker of glomerular filtration rate (GFR), are less influenced by muscle mass than creatinine, offering improved diagnostic accuracy in AKI and early CKD.
- In CKD, biomarkers in blood and urine help stage disease severity, predict progression, and guide therapeutic interventions. Albuminuria, measured as the urinary albumin-to-creatinine ratio (ACR), is a well-established biomarker of glomerular injury in diabetic nephropathy and other CKDs. Blood biomarkers like serum cystatin C and beta-2 microglobulin provide estimates of GFR, complementing creatinine-based equations. Novel biomarkers, such as urinary uromodulin, a protein produced by healthy tubular cells, inversely correlate with CKD progression, while fibroblast growth factor 23 (FGF23) in blood reflects phosphate dysregulation and predicts cardiovascular risk in CKD. Inflammatory markers like C-reactive protein (CRP) and pro-inflammatory cytokines (e.g., IL-6) in blood are associated with CKD progression and complications, highlighting the role of systemic inflammation.
- Emerging biomarkers in kidney injury include nucleic acids and metabolites detected through genomics, proteomics, and metabolomics. MicroRNAs (miRNAs), such as miR-21, are dysregulated in blood and urine during AKI and CKD, offering diagnostic and prognostic potential. Metabolomic profiling identifies urinary metabolites like trimethylamine N-oxide (TMAO) as markers of CKD progression and cardiovascular risk. Circulating cell-free DNA (cfDNA) in blood may reflect renal cell damage, though its role in kidney injury is still under investigation. Composite biomarker panels, combining markers like NGAL, KIM-1, and IL-18, improve diagnostic and prognostic accuracy by capturing diverse aspects of renal pathology, such as tubular injury, inflammation, and fibrosis.
- The discovery and validation of kidney injury biomarkers face challenges, including biological variability, assay standardization, and integration into clinical workflows. Factors like age, sex, comorbidities (e.g., diabetes), and medication use can influence biomarker levels, necessitating normative data. Analytical platforms like enzyme-linked immunosorbent assay (ELISA), mass spectrometry, and quantitative PCR drive biomarker detection, but pre-analytical factors, such as sample storage, can affect results. Regulatory approval, such as by the FDA, requires evidence of clinical utility, as seen with NGAL’s approval for AKI risk assessment in specific settings. Despite their promise, limitations include cost, accessibility in low-resource settings, and the need for longitudinal studies to confirm prognostic value. Future research aims to refine biomarker panels, integrate them with artificial intelligence for predictive modeling, and expand their use in personalized nephrology.
- In summary, biomarkers in kidney injury, detected in blood and urine, are transforming the management of AKI and CKD by enabling early detection, precise diagnosis, and tailored therapies. From established markers like NGAL and albuminuria to emerging nucleic acids and metabolites, these biomarkers address the shortcomings of traditional renal function tests. Continued advancements in technology and validation will enhance their clinical impact, improving outcomes for patients with kidney injury through timely and individualized care.
