Interference of urine tubular biomarker measurements by glycosuria: implications when using SGLT2 inhibitors

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are recommended for use in adults with chronic kidney disease (CKD) and are widely prescribed. SGLT2 inhibition markedly increases urine glucose excretion, which could interfere with laboratory assays. We assessed whether assays for several key urine tubular biomarkers (alpha-1 microglobulin [1M], dickkopf-3 [DKK-3], epidermal growth factor [EGF], interleukin-18 [IL-18], kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], uromodulin [UMOD], and human cartilage glycoprotein-40 [YKL-40]) are affected by glycosuria using urine samples from participants with CKD. Each urine sample was divided into three aliquots, with one serving as control and the other two being spiked with glucose to reach effective concentrations of 28 mmol/l and 111 mmol/l. There was large positive mean bias [95% CI] observed at 28 mmol/l glucose concentration for IL-18 (0.10 [0.01, 0.23]) and YKL-40 (0.40 [0.32, 0.49]). The limits of agreement (LOA) for both biomarkers were wide, spanning >1 unit difference in log-transformed biomarker values. The rest of the biomarkers had narrow LOA. Modest negative mean bias at 28 mmol/l glucose concentration was observed for DKK-3 (-0.02 [-0.04, 0]), KIM-1 (-0.04 [-0.06, -0.02]), and UMOD (-0.08 [-0.11, -0.06]), with similar values observed at 111 mmol/l glucose concentration. There was no evidence of any bias in measurements of 1M, EGF, MCP-1, and NGAL. Glycosuria substantially interferes with IL-18 and YKL-40 measurements, without importantly affecting 1M, DKK-3, EGF, KIM-1, MCP-1, NGAL or UMOD.