Predicting Progression in Diabetic Nephropathy New Biomarker s

Predicting Progression in Diabetic Nephropathy: New Biomarker: s. TNFR 1* Circulating soluble Tumor Necrosis Factor Receptor 1

Diabetic Nephropathy: The Facts Diabetic nephropathy is the leading cause of End Stage Renal Disease (ESRD) worldwide 40% of diabetic patients will develop symptoms of diabetic nephropathy >90% of these will not progress to ESRD, but we are not yet able to predict which patients will progress and which patients will not. Average life expectancy for a patient on Dialysis is < 5 yrs Reference: USRDS 2013

What is soluble Tumor Necrosis Factor Receptor 1 (TNFR 1)? TNFα: Cytokine TNFα is a transmembrane protein generated by many cells, including endothelial cells and leukocytes Implicated in the pathogenesis of diabetic kidney disease The receptors TNFR 1 (and TNFR 2) binds TNFα to mediate activate inflammatory and stress response pathways

s. TNFR 1 improves risk prediction in Diabetic Nephropathy (leading to ESRD) Current Tests Albuminuria (Micro / Marco) Glomerular Filtration Rate (estimated GFR) Shortcomings Poor prognostic value Renal decline predates albuminuria Unstable and highly variable s. TNFR 1 provides additional information on risk in the same way Cholesterol provides information on CVD risk

s. TNFR 1 predicts ESRD within 3 -12 years in type 2 diabetes patients with proteinuria (>300 mg/day) “For patients with s. TNFR 1 levels > 2000 pg/ml , the risk of progression to ESRD was nearly 80% in 12 years” Niewczas et al Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 Diabetes. pdf

s. TNFR 1 predicts ESRD over 10 - 12 years of follow up in type 2 diabetes patients without proteinuria. “For patients without proteinuria, C-Index for s. TNFR 1 was 0. 93 whereas that for albumin excretion rate was only 0. 78 (P=0. 048)” Niewczas et al Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 Diabetes. pdf

s. TNFR 1 prediction of ESRD replicated in independent cohort for type 2 diabetics with CKD Survival Distribution Function Q 1 Q 2 Q 3 Q 4 Follow up period (months) “The risk of renal event was greater in those people from the fourth quartile compared with those in the first to third quartiles, even after multiple adjustments” Reproduced from oral presentations of: Association of Serum Concentration of TNFR 1 With All. Cause Mortality (and Renal Decline) in Patients With Type 2 Diabetes and Chronic Kidney Disease: Follow-up of the SURDIAGENE Cohort. pdf

Conclusions Diabetic nephropathy is leading cause of End Stage Renal Disease (ESRD), but we can’t predict which patients will progress or not progress to ESRD s. TNFR 1 identify which T 2 DM patients are at highest risk of ESRD Combining s. TNFR 1 and urine Albumin Creatinine Ratios gives best predictive value European Association for the Study of Diabetes algorithms suggest Multimodal therapy combining hypoglycaemic agents, statins & ACE inhibitors for patients with diabetic kidney disease

References Year Title Reference 2012 Circulating TNF Receptors 1 and 2 predict ESRD in Type 2 Diabetes JASN Niewczas et al. 2014 Association of Serum Concentration of TNFR 1 With All. Cause Mortality (and Renal Decline) in Patients With Type 2 Diabetes and Chronic Kidney Disease: Follow-up of the SURDIAGENE Cohort Diabetes Care Saulnier et al. 2012 Circulating TNF receptors 1 and 2 predict stage 3 CKD in Type 1 Diabetes JASN Ghoda et al. 2014 Added Value of Soluble Tumor Necrosis Factor Alpha Receptor-1 as a Biomarker of ESRD Risk in Patients With Type 1 Diabetes Care Forsblom et al.