Chronic kidney disease is a significant complication of diabetes that affects >35% of patients and is a major cause of renal transplantation globally with 10-20% of diabetics dying of kidney failure. The current diagnostic test for diabetic kidney disease uses a single urine biomarker that measures microalbumin levels (albumin/creatinine ratio, ACR) which has limited utility. Clinicians require better tools that deliver a more effective diagnosis, prognosis and monitor treatment to notably improve health outcomes.

A panel of 12 candidate biomarkers were identified by mass spectrometry in a pilot study of 90 highly curated clinical samples. A further diagnostic study analysing 572 individuals has validated protein biomarkers at high stringency using mass spectrometry, including proteins involved in metabolism, inflammation and oxidative stress. Cross-validation of these findings against antibody-multiplexing approaches has yielded highly significant correlations between biomarker levels and the ACR and eGFR measurements of these patients. Specific ROC curves were constructed for combinations of biomarkers that show that the panel can discriminate different risk categories of diabetic kidney disease.

The final prognostic dataset was collected from 349 patients at three key time points (Years 0, 2, 4). The statistical analysis of this data revealed the predictive ability of the biomarker panel to determine which patients were at risk of significant and rapid decline in kidney function better than any other known measure. The preferred model of 3 biomarkers as a predictor of eGFR decline had an AUC of 0.83 with 89% sensitivity, 68% specificity. People who have altered levels of protein from the biomarker panel are up to 7 times more likely to be in the eGFR decliner trajectory group.

PromarkerD as a panel of biomarkers for diabetic kidney disease has the ability to both diagnose existing disease where the current measures are inadequate and predict future significant decline in kidney function. The target outcome is a point-of-care test or companion diagnostic for diabetic kidney disease.