P3.3 THE CKD273 URINARY PROTEOMIC BIOMARKER FOR EARLY DIAGNOSIS OF DIABETIC NEPHROPATHY DOES NOT INDICATE GENERALISED SUBCLINICAL VASCULAR DISEASE IN NORMOALBUMINURIC TYPE 2 DIABETIC PATIENTS

Background: Diabetic nephropathy (DN) is associated with cardiovascular disease. Microalbuminuria (MA), its traditional hallmark, reflects both renal and generalised vascular damage. We previously established a urinary proteomic classifier (CKD273) for early DN prediction that correlates with other biomarkers of renal function. Whether CKD273 only indicates renal damage or also generalised vascular disease remains unclear. Methods: We recruited 80 patients with type 2 diabetes (age, 62±7 years; blood pressure 138±11/79±8mmHg) free from cardiovascular complications with normal renal function (eGFR (88±15 ml/min/1.73m2) and normoalbuminuria (albumin: creatinine ratio (UACR), 5 (2-16) mg/g). Participants underwent measurement of carotid-femoral pulse wave velocity (PWV; SphygmoCor) and carotid intima media thickness (cIMT; ultrasound). Urinary proteomic analysis was performed by capillary electrophoresis coupled to mass spectrometry. Results: Mean CKD273 score (−0.234±0.376) was well below the pre-established cut-off (0.343) for diagnosis of DN. There was a trend towards higher CKD273 score in patients with UACR above the median (−0.160±0.372 vs −0.318±0.368; P=0.061). Median time from diabetes diagnosis was 11 (1–30) years; diabetes control was suboptimal (HbA1c, 62 (45–102) mmol/mol); and participants had subclinical vascular damage (PWV, 9.2 (6.4–12.5) m/s; cIMT, 0.850 (0.543–1.292) mm). As expected we saw a significant correlation between PWV and systolic blood pressure (r=0.259; P=0.024). The CKD273 classifier did not correlate with PWV (r=0.174; P=0.132) or cIMT (r=−0.096; P=0.415). Conclusion: CKD273 is not a marker of subclinical macrovascular disease in normoalbuminuric type 2 diabetic patients without overt cardiovascular complications. Our data provide further evidence that CKD273 is a specific marker of renal damage.