Chronic Kidney Disease

Biomarkers for chronic kidney disease (CKD)

Chronic kidney disease (CKD) is a long-term condition where the kidneys gradually lose function over time, often without noticeable symptoms in the early stages. CKD affects over 800 million people worldwide and is a major driver of morbidity, mortality, and healthcare costs. Early identification of patients at risk of rapid progression is essential to improve outcomes and tailor therapeutic interventions.

The most widely used and accepted clinical markers to predict the progression of CKD are eGFR and albuminuria, but they often fail to detect early or dynamic changes in disease activity. Biomarkers offer a powerful solution by providing mechanistic insights into underlying pathophysiology. Biomarkers related to the extracellular matrix (ECM) reflect ongoing tissue remodeling and fibrosis—key processes driving CKD progression. ECM biomarkers can predict disease trajectory more accurately than conventional measures alone.

Why Nordic ProteinFingerPrint™ Biomarkers in CKD?

Our biomarker assays quantify ECM fragments released into the blood or urine during active fibrogenesis and fibrolysis. They provide dynamic and disease-relevant insights into tissue formation, degradation, and fibrosis resolution—offering a clearer window into the pathological processes driving kidney disease. Unlike broad-spectrum omics or proteomics approaches, our biomarkers are highly specific to ECM remodeling, enabling more precise detection of fibrotic activity.

ECM remodeling is a key feature of fibrosis, which is a central mechanism in CKD progression. By directly measuring ECM-derived biomarkers, we can assess the extent of fibrosis and of fibroblast activity and its potential impact on kidney function. This allows for earlier identification of patients at risk of rapid decline and enables more targeted therapeutic strategies. Our approach supports better patient stratification and enhances decision-making in clinical trials and drug development.

Reduced type III collagen degradation indicates increased risk for kidney-related outcomes and mortality

A well-regulated ECM is essential for maintaining kidney tissue structure and homeostasis. In the kidney, the ECM is organized into three key compartments: the tubulointerstitial matrix, the glomerular basement membrane (GBM) that supports endothelial cells, and the tubular basement membrane that supports epithelial cells, as well as the mesangial matrix within the glomerulus.
Under normal conditions, the tubulointerstitial matrix contains only low levels of fibrillar collagens, such as type III collagen. However, during fibrosis, there is a marked upregulation of type III collagen. This excessive accumulation in the interstitial space contributes to tissue scarring, disrupts normal architecture, and leads to progressive loss of kidney function.

In the Renal Impairment in Secondary Care (RIISC) study, reduced levels of type III collagen degradation in CKD patients (n=498) have shown to be associated with increased risk of end-stage kidney disease (ESKD), illustrated in Figure 1.

Figure 1. Reduced type III collagen degradation indicates increased risk for kidney-related outcomes and mortality

Elevated fibroblast activity and type VI collagen formation are associated with severity of CKD and tubulointerstitial fibrosis

Type VI collagen is located near the basement membrane and has several bindings sites for basement membrane proteins. Upon maturation of new type VI collagen molecules produced by highly activated fibroblasts, a bioactive fragment called Endotrophin is released. Endotrophin has pro-fibrotic, pro-tumorigenic and pro-inflammatory signalling roles. We measure nordicEndotrophin™ and formation of type VI collagen with our biomarker nordicPRO-C6™ (PRO-C6).

In Figure 2, the Kaplan-Meier plot illustrates the probability of survival over time among participants with CKD, stratified into quartiles based on their serum PRO-C6 levels. Participants in the highest quartile had a 12-fold increased risk of death relative to the lowest quartile. Figure 3 reinforces the findings from Figure 2, providing statistical evidence that higher serum PRO-C6 levels independently predict increased mortality risk in CKD patients. The robustness of this association, despite adjustment for multiple confounding variables, highlights the potential of PRO-C6 as a valuable biomarker in clinical risk assessment. Altogether, these findings suggest that PRO-C6 could be a promising biomarker for identifying high-risk individuals and guiding therapeutic interventions.

Figure 2 and 3. Elevated fibroblast activity and nordicPRO-C6™ are associated with severity of CKD and tubulointerstitial fibrosis

About chronic kidney disease (CKD)

  • Chronic kidney disease (CKD) is a progressive condition marked by the gradual loss of kidney function. Early detection is critical because many patients show no symptoms until advanced stages. Identifying at-risk individuals early allows for timely intervention to slow progression and improve outcomes.

  • Biomarkers provide non-invasive and dynamic insight into tissue-level changes such as fibrosis and inflammation. Unlike traditional markers like eGFR and albuminuria, ECM-derived biomarkers can detect early disease activity and offer more accurate predictions of progression and treatment response.

  • ECM remodeling involves the breakdown and formation of structural proteins like collagen in the kidney. In CKD, dysregulated ECM remodeling leads to fibrosis, disrupting kidney function. Measuring specific ECM biomarkers gives a direct readout of fibrotic activity and disease progression.

  • Nordic ProteinFingerPrint™ biomarkers offer high specificity for ECM changes, making them ideal for patient stratification, risk assessment, and pharmacodynamic monitoring in CKD trials. Their ability to detect fibrosis activity supports more informed therapeutic development and decision-making.

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    Nordic Bioscience’s assays and services are research use only products and services and do not qualify for medical or diagnostic purposes.