Identifying Urine Biomarkers of Chronic Kidney Disease

Urine biomarkers can offer early insights into chronic kidney disease (CKD). Using Causaly, Retinol-Binding Protein 4 (RBP4) was identified as a potential urine biomarker of CKD progression with untapped potential.

Chronic Kidney Disease (CKD) is a progressive kidney disorder affecting over 800 million people worldwide.¹ If left untreated, CKD can advance to end-stage renal disease, necessitating disease management through dialysis or kidney transplantation.²

Monitoring disease progression is crucial for timely interventions in CKD. Established clinical biomarkers of CKD include serum creatinine and glomerular filtration rate (GFR).³ However, alterations in these biomarkers often only become apparent after significant kidney damage, and their limitations in accurate prediction of renal injury are well known.⁴

Urine biomarkers are particularly valuable, offering a non-invasive method to monitor CKD progression and detect renal abnormalities earlier than some blood biomarkers.⁵ In this use case, we have used Causaly to identify potential urine biomarkers for CKD.

Approximately 3,000 potential biomarkers associated with CKD were identified using Causaly. Around 850+ biomarkers of CKD in urine were uncovered, 200+ of which were associated with disease progression. From 2022 to date, around 60 urine biomarkers of CKD disease progression have been reported, according to Causaly. Retinol binding protein 4 (RBP4) was among the biomarkers with the strongest evidence (Figure 1).

RBP4, also known as RBP, is the primary carrier protein for retinol (vitamin A) in blood. It is predominantly expressed by hepatocytes and adipose tissue, delivering retinol from the liver to surrounding tissues.⁶

Urinary RBP4 has emerged as a highly sensitive indicator of renal tubular damage,⁷ including in the context of CKD.⁸ A 2022 study involving 305 diabetic nephropathy patients found that urinary levels of RBP4 correlated with the severity of interstitial fibrosis and tubular atrophy.⁹ Additionally, urinary RBP4 was identified as a significant and independent risk factor for stage 5 CKD.⁹ Given these findings, monitoring RBP levels in urine could be crucial for timely interventions and improved outcomes in patients at risk of severe renal complications.

Urine biomarkers, such as RBP4, offer potential in CKD detection and disease tracking. While current clinical markers have limitations, novel biomarkers may enhance disease management. Continued research could further optimize non-invasive CKD management and patient outcomes.