Urinary growth differentiation factor 15 predicts renal function decline in diabetic kidney disease

Background: Sensitive biomarkers can enhance the diagnosis, prognosis, and surveillance of chronic kidney disease (CKD), such as diabetic kidney disease (DKD). Plasma growth differentiation factor 15 (GDF15) levels are a novel biomarker for mitochondria-associated diseases; however, it may not be a useful indicator for CKD as its levels increase with declining renal function. This study explores urinary GDF15’s potential as a marker for CKD. Methods: The plasma and urinary GDF15 as well as 15 uremic toxins were measured in 103 patients with CKD. The relationship between the urinary GDF15-creatinine ratio and the uremic toxins and other clinical characteristics was investigated. Results: Urinary GDF15-creatinine ratios were less related to renal function and uremic toxin levels compared to plasma GDF15. Additionally, the ratios were significantly higher in patients with CKD patients with diabetes (p = 0.0012) and reduced with statin treatment. In a different retrospective DKD cohort study (U-CARE, n = 342), multiple and logistic regression analyses revealed that the baseline urinary GDF15-creatinine ratios prediceted a decline in estimated glomerular filtration rate (eGFR) over two years. Conclusions: Compared to the plasma GDF15 level, the urinary GDF15-creatinine ratio is less dependent on the renal function and sensitively fluctuates with diabetes and statin treatment. It may serve as a better prognostic marker for renal function decline in patients with DKD than the urine albumin-creatinine ratio.