Test Strip–Positive Proteinuria and Its Combination with Low eGFR Are Predictive of Treatment-Required Eye Diseases in Japanese Patients with Diabetes Mellitus

Abstract

Proteinuria or low eGFR was separately shown to be associated with the development of retinopathy in patients with diabetes. However, it remains unclear whether semi-quantitatively assessed proteinuria by test strips either combined or not combined with low eGFR is predictive of incident retinopathy, especially in its advanced stages.To clarify this, we utilized ICD-10 and medical treatment codes from a nationwide claims database that included 6,100 participants (1,074 women, mean age 49.3 y, HbA1c 6.9%) classified as having diabetes mellitus or treatment-required diabetic eye diseases (TRDED) during an 8-y period. Urinary protein was assessed by test strip and a result of ≥1+ indicated proteinuria, which reportedly corresponds to a urine protein concentration of ≥30 mg/dL. Multivariate Cox regression model was used to identify predictors of TRDED. During the study period, 147 patients developed TRDED (4.5/1000 person-years). Cox analysis showed that proteinuria was a significant and independent predictor of TRDED but not the serum creatinine level. Hazard ratios (HRs) for proteinuria, low eGFR (defined as <45 mL/min/1.73m2) and HbA1c (per 1% increment) for incident TRDED were 2.37(95% CI, 1.59-3.53), 3.95(1.56-10.01), and 1.73(1.55-1.94), respectively. Compared with participants with neither proteinuria nor low eGFR, those with proteinuria but not low eGFR and those with both proteinuria and low eGFR had 2.21 (1.46-3.34) and 13.82(5.50-34.71), respectively, times higher risk for TRDED. These results implied that proteinuria worked synergistically with low eGFR but the interaction was not statistically significant. These findings demonstrated that semi-quantitatively assessed proteinuria using test strips is quick and useful for assessing the risk of development of advanced retinopathy especially in combination with reduced eGFR. Disclosure M. Yamamoto: None. K. Fujihara: None. T. Osawa: None. M. Harada: None. M. Ishizawa: None. H. Ishiguro: Research Support; Self; MSD K.K., Sanofi K.K., Eli Lilly and Company. H. Suzuki: None. H. Seida: None. N. Yamanaka: None. Y. Matsubayashi: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..