Urine albumin-to-creatinine ratio as a predictor of kidney function decline in Alport syndrome

BACKGROUND: Chronic kidney disease significantly impacts health and lifespan, but its progression remains difficult to predict. Therefore, there is a need for biomarkers to identify patients at risk of a rapid decline in kidney function. Alport syndrome (AS) exemplifies this challenge, as some patients experience rapid progression, while others exhibit a more gradual decline in kidney function. We hypothesized that urinary proteins, such as albumin, immunoglobulin G (IgG), or alpha-1-microglobulin, could serve as predictors of kidney function decline. METHODS: This observational, non-interventional, retrospective study investigated 127 patients with AS from two centres. Yearly estimated glomerular filtration rate (eGFR) loss was modelled in a linear regression model. RESULTS: Over a 42 ± 26-month follow-up, 24% of the patients had rapid eGFR decline (defined as a loss of >6 ml/min/1.73 m² per year). Urinary albumin-to-creatinine ratio (UACR) showed the highest negative correlation with the change in eGFR (ρ = -0.435, P < 0.001; n = 109). After adjusting for age, gender, renin-angiotensin system inhibition, mode of inheritance, and eGFR, UACR was independently associated with the yearly eGFR loss (P < 0.001). Urinary IgG had the highest sensitivity in identifying patients with kidney function decline. CONCLUSION: In this study, the amount of albuminuria was independently associated with the yearly loss of kidney function in patients with AS. Combined measurement of albuminuria and urinary IgG may identify patients with the highest risk of rapid decline in kidney function. Following external validation in a larger, prospective cohort, this approach could be used to identify patients who could potentially benefit from closer monitoring and earlier intervention.