Dr. Somaya Zahran is a Nephrology fellow and Chief Fellow at McGill University in Montreal, Canada. She earned her medical degree in Egypt and completed a PhD at the University of Alberta. She went on to complete her internal medicine residency and nephrology fellowship at McGill University, serving as Chief Resident in both programs. Dr. Zahran’s interests span kidney transplantation, health equity, and clinical guideline development. She is an active trainee member of the Canadian Society of Nephrology Clinical Practice Guideline Committee. In July 2025, she will begin a Transplant Nephrology Fellowship at the Mayo Clinic in Rochester, Minnesota. Dr. Zahran is a 2024-25 Editorial Intern.

Chronic kidney disease (CKD) is one of the most prevalent morbidities and soon will be one of the leading causes of death worldwide. Its severity has been historically measured by quantification of estimated glomerular filtration (eGFR) decline and quantification of urinary albumin. Risk scores integrating demographics, comorbidities, and biochemical indicators to stratify patients and estimate the risk of progression have been developed. Tools like kidney failure risk equation (KFRE) have been validated in different CKD cohorts with good predictive ability. Yet, many CKD patients progress in an unpredictable manner. While this could be partially related to the heterogeneous pathophysiology underlying CKD development and progression and the variable external factors that play a major role in CKD deterioration (i.e. diet, acute illness, medications, etc.), the limitations related to current risk prediction scores call for novel parameters that could better capture the disease trajectory and enhance these models to allow for more personalized interventions.

Afamin is a vit-E binding protein that belongs to the albumin gene family, synthesized by the liver, and can be found primarily in the serum and, to a lesser extent, in the urine. Afamin is involved in the extracellular transport of vitamin E (α-tocopherol), particularly in aqueous environments such as plasma and cerebrospinal fluid, and is believed to contribute to systemic antioxidant defense. It has also been implicated in facilitating signaling pathways and cellular homeostasis. Higher levels of plasma afamin have been correlated with metabolic syndrome while urinary afamin has been linked to renal diseases. A recent study published in AJKD by Kollerits et al. explores afamin as a novel biomarker for CKD progression.

The study analyzed 5,041 patients with CKD from the German Chronic Kidney Disease (GCKD) cohort with CKD stage G3 or A3 over 6.5 years where serum afamin concentrations were examined in relation to the incidence of a composite renal failure endpoint (dialysis, transplant, or kidney-related death). Higher afamin levels correlated with higher eGFR and lower albuminuria. Mean afamin concentration was 73 mg/L and each 10 mg/L higher than the mean level was associated with 2.6 mL/min/1.73 m²  higher eGFR (95% CI 2.3-2.89) and 5.97 mg/g lower albuminuria (95% CI 3.04-8.9). Furthermore, by the end of the 6.5 year follow-up period, individuals with higher afamin concentration had less composite renal failure events (HR 0.86, 95% CI 0.81-0.92, P<0.001). Notably, this was independent of diabetes mellitus status, HbA1C, and the use of antihypertensive medications.

Knowing this, does afamin then have the potential to be integrated in a CKD predictive model and improve its accuracy? The authors examined the impact of adding afamin as a variable to KFRE and the Z6 risk prediction tool developed by Zacharias et al. and tested the updated models on the cohort that progressed into kidney failure. Both models’ performance improved, showing that afamin could help make risk predictions more accurate.

However, the study cannot be generalised beyond the examined population, i.e. Caucasian patients with stage G3 or A3 CKD. Additionally, the modified risk prediction tools -after adding afamin- have not been externally validated and should be interpreted with caution. Even though the association is compelling, one can not infer whether higher afamin concentrations are a reflection of better kidney health vs. reno-protective in nature. In any case, further standardization of afamin assays will be needed before further adaptation into clinical practice.

This study might seem to controvert with previous literature which showed that urinary afamin concentrations are related to worse renal health. The authors attribute this to the small sample sizes and limited number of prior studies and provide speculative explanations based on antioxidative properties for afamin that could be linked to its structural similarities to albumin, as well as its well-established role in binding two proposed antioxidative molecules; vit E and tocopherol. There is so much still to be learned about afamin and this study highlights the fact that afamin concentration interpretation is not straightforward and could be context-dependent, i.e. reflecting antioxidative benefit in individuals without significant concurrent illness vs. underlying inflammatory stress in high cardiometabolic disease burden. More studies are needed to examine the right context of afamin correlation with kidney health and identify the thresholds that reflect beneficial elevations vs. harmful accumulation.

The current challenge of predicting CKD progression is likely not going to be solved by just one perfect biomarker. Despite the uncertainties, afamin represents an exciting step forward in the quest for better CKD biomarkers and the study shows the importance of thinking beyond nephrology borders, integrating biomarkers extrapolated from other chronic conditions that might share similar pathophysiological concepts of progression with CKD. As shown in Figure 1, afamin is one of several emerging biomarkers being explored to fill the gaps left by traditional tools in predicting CKD progression. In the broader context, the pursuit of new biomarkers reflects a larger movement in medicine toward early detection and prevention of chronic diseases. Afamin may not be the definitive answer, but it represents progress; a new piece of the puzzle that could bring us closer to a future where CKD progression is more predictable, preventable, and manageable.

Figure 1. Current and emerging biomarkers in CKD assessment. © Somaya Zahran.