Table 1. A systemic assessment of diagnostic tools aid in achieving precise medical management: PRIORITY trial and CKD273 biomarker as prototypes.

	Criterion	Examples from PRIORITY and other studies with CKD273
Precision	Populations and settings	PRIORITY studied patients with T2D, normoalbuminuria (UACR <30 mg/g) and eGFR >45 mL/min/1.73 m2 and explored whether CKD273 marker can predict risk for new persistent albuminuria. Others investigated the diagnostic utility of CKD273 in different DKD stages and in patients with non-diabetic CKD, including its ability to serve as a non-invasive substitute for kidney biopsy (15)
	Reliability	Baseline CKD273 was tested once in PRIORITY. Previous analysis of a small cohort showed relatively low inter- and intra-assay standard deviation (below 10%), as well as low inter-laboratory variability (rank correlation coefficients between three labs of 0.881–0.904). Acute nephrolithiasis and to some extent ACEi treatment were associated with positive CKD273 results (37% and 9% respectively) (15,17)
	Improved specificity and sensitivity	In PRIORITY, CKD273 statistically improved prediction of new onset albuminuria, on top of a predictive model composed of other baseline markers (AUC =0.78 vs. 0.76), resulting in sensitivity of 30.5%, specificity of 90.2% and positive predictive value of 28.2%
Availability	Widely distributed technology and know-how	CKD273 requires sophisticated infrastructure, currently employed in three laboratories worldwide (16)
	Cost effective	CKD273 test is costly (~850€) (16). Cost-effectiveness analysis on hypothetical cohorts showed that although CKD273 is costlier than UACR, its use may result in more quality-adjusted life years when applied to high-risk populations (15). PRIORITY’s data can be utilized to further address this issue on real life cohorts
Outcome	Predicts patient’s outcome	PRIORITY has proven that CKD273 predicts occurrence of new onset albuminuria in its settings. Increased CKD273 was also associated with a decline in kidney function, and with non-significant trends towards worse CV outcomes
	Follow-up and re-evaluation by sequential testing	Small studies indicated that urinary proteome in patient with diabetes is affected by renal protective therapies (irbesartan or empagliflozin), indicating reversibility of fibrotic changes in DKD. Similar findings were observed in some patients with non-diabetic CKD (15). In PRIORITY, CKD273 was reported only at baseline
	Provides pathophysiological insights	Urinary proteomic signatures implicated several proteins and processes in DKD pathology, e.g., collagen fragments, tubuli-originated uromodulin, α1-antitrypsin, clusterin and more (14,15). Further analysis of PRIORITY data that combines proteomic analysis with high quality follow-up is expected to expand our understanding of DKD’s pathophysiology
	Predicts response to specific drug	In a small trial CKD273 was found to predict the reduction in albuminuria as a response to spironolactone (15). Exploratory analysis of PRIORITY data, and possibly future studies, can test other renal protective drugs
	Affects clinical management and outcome	This is the main secondary objective of PRIORITY. Spironolactone treatment for patients with high baseline CKD273 did not reduce the occurrence of microalbuminuria, but was associated with high adverse-events related dropouts. Nonetheless, further investigation is warranted with new renal protective possibilities