MO649DIAGNOSTIC TESTS OF NOVEL URINARY BIOMARKERS TO IDENTIFY EARLY STAGES OF NEPHROPATHY IN NON HYPERTENSIVE TYPE 2 DIABETIC MELLITUS

Background and Aims Activation of RAS and tubulointerstitial damage might be seen in pre-albuminuria stage of diabetic nephropathy. Here, diagnostic tests of urinary Angiotensinogen, Cystatin C, Neutrophil gelatinase associated lipocalin and IL 18 have been studied in pre-microalbuminuria diabetic patients. Method Total 952 Diabetic screened for Nephropathy (e-GFR ≥120&ACR≥30), among them 120 cases were followed up for one year. At one year they were classified in to Hyperfiltration43, Normoalbuminuria29 and Microalbuminuria48 groups. Another 63 Diabetes without nephropathy were included as controls. Hypertension, on ACEI/ARB, e-GFR<60ml/min/1.73m2 and all Macroalbuminuria conditions were excluded. All were subjected to urine protein, ACR, HbA1c,e-GFR, along with urinary bio markers(IL-18, Cystatin-C, NGAL and Angiotensinogen). Comparative analysis of all groups, Diagnostic tests, correlation and logistic regression were analysed. Results Urinary IL18/Cr, Cystatin /Cr. and Angiotensiogen /Cr. levels were higher in groups of hyper filtration (13.47, 12.11 & 8.43mg/g), Normoalbuminuria (9.24,11.74&9.15mg/g) and microalbuminuria(11.59,14.48&10.24mg/g) than controls(7.38,8.39&1.26mg/g) but not NGAL/Cr. in all groups. High levels were significant in all except Cystatin/Cr. & IL18/Cr. in normoalbuminuria group. The AUC, sensitivity and specificity of Angiotensinogen (0.9, 90% and 80%) ACR (0.69, 40% and 100%) and e-GFR (0.6,37 and 100%)respectively. AUC of other biomarkers viz, IL 18/cr. Cystatin/Cr and NGAL/Cr. were 0.65, 0.64 and 0.51 respectively. Angiotensinogen/Cr and IL18/Cr showed correlation with log albuminuria r-0.3 p 0.00 and r-0.28 p 0.00 respectively; NGAL with log e-GFR (r-0.28 p0.00).Multivariate logistic analysis showed Odds of contracting nephropathy is 7.5 times having higher values of Log Angio/Cr. Conclusion Urinary Angiotensinogen has higher diagnostic value than ACR and e-GFR followed by IL 18 and Cystatin to diagnose DN at the pre-albuminuric stages but not urinary NGAL.

Urinary angiotensinogen as a surrogate marker predicting the antiproteinuric effects of angiotensin receptor blockers in patients with overt proteinuria: a multicenter prospective study

Background: Although urinary angiotensinogen (AGT) and renin reflect intrarenal renin-angiotensin system activity and are enhanced in proteinuric chronic kidney disease, the clinical value of urinary AGT and renin levels during antiproteinuric treatment has yet to be determined. We investigated the clinical usefulness of initial urinary AGT or renin to determine the antiproteinuric effects of angiotensin receptor blockers (ARBs). Methods: This multicenter, prospective, single-arm study included 205 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] ≥ 1 mg/mg) enrolled between April 2009 and December 2011. All patients were treated with valsartan. The urinary AGT/creatinine ratio (uAGT/Cr) was measured at the baseline and 24 weeks, and the renin/creatinine ratio (uR/Cr) was measured at the baseline. Fifty-six patients were followed-up for 5 years. Results: The mean age was 47.6 years and 51.2% were male. The mean uPCR was 2.32 mg/mg and the mean eGFR was 63.2 mL/min/1.73m2. Natural logarithms (ln) (uAGT/Cr), ln(uR/Cr), and diabetes mellitus were associated with proteinuria decrement (decrease in uPCR ≥ 1 mg/mg). Ln(uAGT/Cr) was an independent predictor for proteinuria decrement (OR 1.372, 95% CI, 1.068–1.762, P = 0.013). Among the 56 patients followed-up for 5 years, Δln(uAGT/Cr) at 24 weeks was an independent predictor for uPCR < 1 mg/mg at 5 years (OR 0.379, 95% CI, 0.20–0.715, P = 0.003). Conclusions: Our study demonstrates the potential role of both baseline urinary AGT and changes in urinary AGT during the initial 24 weeks as surrogate markers predicting the antiproteinuric effects of ARBs in patients with overt proteinuria.

Urinary angiotensinogen as a surrogate marker predicting the antiproteinuric effects of angiotensin receptor blockers in patients with overt proteinuria: a multicenter prospective study

Background: Although urinary angiotensinogen (AGT) and renin reflect intrarenal renin-angiotensin system activity and are enhanced in proteinuric chronic kidney disease, the clinical value of urinary AGT and renin levels during antiproteinuric treatment has yet to be determined. We investigated the clinical usefulness of initial urinary AGT or renin to determine the antiproteinuric effects of angiotensin receptor blockers (ARBs). Methods: This multicenter, prospective, single-arm study included 205 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] ≥ 1 mg/mg) enrolled between April 2009 and December 2011. All patients were treated with valsartan. The urinary AGT/creatinine ratio (uAGT/Cr) was measured at the baseline and 24 weeks, and the renin/creatinine ratio (uR/Cr) was measured at the baseline. Fifty-six patients were followed-up for 5 years. Results: The mean age was 47.6 years and 51.2% were male. The mean uPCR was 2.32 mg/mg and the mean eGFR was 63.2 mL/min/1.73m2. Natural logarithms (ln) (uAGT/Cr), ln(uR/Cr), and diabetes mellitus were associated with proteinuria decrement (decrease in uPCR ≥ 1 mg/mg). Ln(uAGT/Cr) was an independent predictor for proteinuria decrement (OR 1.372, 95% CI, 1.068–1.762, P = 0.013). Among the 56 patients followed-up for 5 years, Δln(uAGT/Cr) at 24 weeks was an independent predictor for uPCR < 1 mg/mg at 5 years (OR 0.379, 95% CI, 0.20–0.715, P = 0.003). Conclusions: Our study demonstrates the potential role of both baseline urinary AGT and changes in urinary AGT during the initial 24 weeks as surrogate markers predicting the antiproteinuric effects of ARBs in patients with overt proteinuria.