#5438 SERUM TUMOUR NECROSIS FACTOR RECEPTOR 1 PROTEIN ACCURATELY PREDICTS RAPID DISEASE PROGRESSION IN DIABETIC KIDNEY DISEASE

Abstract Background and Aims Diabetic kidney disease (DKD) has an enormous disease burden globally. In the area of personalised medicine, biomarker is set to play an important role in the management of DKD. Prior studies have reported the possible association of Tumour Necrosis Factor Receptor 1 (TNFR1), Dickkopf-3 (DKK3) and B cell lymphoma 3 (BCL-3) with the pathogenesis of DKD. However, there had been no prior studies that investigate the association of these biomarkers as prognostic markers for DKD disease progression. Hence, we aim to investigate the correlation of these biomarkers with renal progression among the diabetic population with and without kidney disease. Method A total of 156 subjects were recruited, which consisted of 64 control vs 92 patients with DKD. The principal outcomes of this study were rapid renal decline (doubling of serum creatinine, renal decline > 5ml/min/year and > 10 ml/min/year) and their association with serum TNFR1, BCL-3 and urine DKK3. A bivariate analysis was used to test the association of rapid renal decline, and sensitivity and specificity were used to test the validity of the level of the biomarkers with outcomes. Results The baseline parameters for both case and control: age 50.19±9.22 vs 60.35±13.73, serum albumin 38.97±2.07 vs 33.01±8.98g/l (p< 0.001), eGFR 117.96±31.94 vs 38.00±22.04 ml/min/ 1.73 m2 (p<0.001), serum creatinine 77.34±14.15 vs 247.45±148.09 µmol/L (p< 0.00), uPCI g/day 0.001±0.0 vs 4.268±5.29 (p< 0.001), HbA1c 7.83±1.88 vs 7.86±1.78 mmol/L (p = 0.942), sTNFR 11781.91±337.46 vs 4394.03±1960.06 pg/mL (p<0.001), uDKK3/creatinine 132.84±37.61 and 1243.63±495.27 pg/mg (p< 0.001), and sBCL3 194.60±32.81 vs 490.17±259.02 pg/mL(p<0.001). During the follow-up, there was a significant association of sTNFR1 with rapid renal decline > 5ml/min/year, > 10 ml/min/year and doubling of serum creatinine [p < 0.003 [IQR = 2891.50-4885.75], p< 0.009 [2891.50-4885.75], p< 0.001 [2891.50-4885.75] but not with uDKK3 and sBCL-3 (Table 1). Specificity and sensitivity analyses on the performance of the biomarkers versus outcomes were highly significant (Figure 1). Conclusion Despite TNFR1, BCL-3 and urine DKK3 were all elevated in our DKD patients, there was a strong association between incident serum TNFR1 level and the subsequent deterioration of renal function which has not been reported in the literature before. In addition, TNFR1 level had consistently picked up cases of DKD that would experience rapid renal progression, be it > 5ml/min/year, > 10 ml/min/year or doubling of serum creatinine. The correlation studies have shown TNFR1 level high sensitivity, and specificity of TNFR1 on the rapid renal function decline. Thus, we believe in our DKD population, targeting TNFR1 pathway could be a promising tool in monitoring and treating our DKD population.