MO512: Association of Urinary Biomarkers and Accelerated, Age-Related Decline in Measured Gfr
Authors: Marie Andreassen Runa , Melsom Toralf , Odvar Eriksen Bjørn , Dahl Solbu Marit 
Published: May 2022

BACKGROUND AND AIMS

Urinary albumin excretion (UAE) is considered as a risk marker for chronic kidney disease (CKD), but the exact pathophysiological mechanisms are not known. Studies have shown that urinary orosomucoid excretion (UOE) is associated with general endothelial dysfunction and atherosclerosis, and UOE is suggested to be a more sensitive marker of GFR decline than albuminuria. In this longitudinal study, we investigated the association between urinary markers (UAE and UOE) and accelerated decline in measured GFR in a middle-aged general population.

METHOD

The Tromsø study is a population-based study with repeated health surveys of inhabitants of Tromsø, Northern Norway. As a part of Tromsø 6, the Renal Iohexol Clearance Survey (RENIS-T6, 2007–9) included participants between 50–62 years old without previous coronary artery disease, diabetes mellitus or kidney disease. Follow-up studies were conducted in 2013–15 (RENIS-FU) and in 2018–2020 (RENIS-R3). GFR was measured by plasma clearance of iohexol.

Urinary specimens from three consecutive days were analysed immediately for albumin and creatinine. Urinary orosomucoid was analysed later after freezing and thawing. Urinary albumin and orosomucoid were divided by the creatinine concentration (UACR: urinary albumin creatinine ratio, UOCR: urinary orosomucoid creatinine ratio) of the same specimen, and median log transformed values were used. The association between UOCR and GFR decline was assessed by linear mixed regression models.

RESULTS

A total of 786 women and 773 men (n = 1559) were included. The mean age was 58 years for both women and men, and mean GFR was 91.1(±12.3) mL/min/1.73 m² for women and 98.2(±13.1) mL/min/1.73m² for men. Men had higher blood pressure, BMI and lower cholesterol as well as higher median UOCR than women (men: 0.36 (IQR: 0.19–0.77) mg/g; women: 0.29 (IQR: 0.19–0.60) mg/g; P = .04), but median UACR was lower in men compared with women (men: 0.25 (IQR: 0.13–0.49) mg/mmol; women: 0.32 (IQR: 0.19–0.59) mg/mmol; P &lt; .001). The median observation time was 5.5 years (IQR: 0–10.5). In the follow-up studies (RENIS-FU, RENIS-R3), we included participants with GFR measurements and urinary markers in 1271 and 1129 participants, respectively.

Adjusted for age and sex, a doubling (log2) of baseline UOCR was associated with a lower GFR of 0.63 mL/min/1.73 m² {P = .002, [95% confidence interval (95% CI) –1.03 to –0.23]}, but no association was found between UACR and GFR (P = .670).

Adjusted for the same variables, each log2 UOCR was associated with an accelerated annual GFR decline of 0.06 mL (P = .011, 95% CI –0.10 to –0.01) throughout the follow-up period. No association was found between log2UACR and accelerated annual GFR decline (P = .107, 95% CI –0.08–0.01).

CONCLUSION

In a population-based study of middle-aged to elderly, relatively healthy men and women with a mean observation time of 8.3 years, we found an association between UOCR and accelerated annual GFR decline adjusted for age and sex. We did not find the same association for UACR. The clinical relevance of this association needs to be studied further.