Tumour Necrosis Factor-alpha Receptor 1 and 2 are Reduced in patients with Type 1 Diabetes and Hyperfiltration — ASN Events

Tumour Necrosis Factor-alpha Receptor 1 and 2 are Reduced in patients with Type 1 Diabetes and Hyperfiltration (#34)

Jas-mine Seah 1 2 , Michele Milne 1 2 , George Jerums 1 2 , Richard J MacIsaac 3 , Ruth Lim* 4 , Elif I. Ekinci* 1 2
  1. Endocrinology, Austin Health, Heidelberg, VIC
  2. Medicine Austin Health, University of Melbourne, Melbourne
  3. Endocrinology, St Vincent's Hospital, Fitzroy, VIC
  4. Radiology, Austin Health, Heidelberg, VIC

Introduction

Soluble Tumour Necrosis Factor-alpha receptors (sTNF-aR) 1 and 2 may improve the prediction of future risk of progression to diabetic kidney disease (DKD) in patients with type 1 (T1DM) and type 2 diabetes. sTNF-aR 1 and 2 may be associated with hyperfiltration, which has not been previously studied. In a prospective cross-sectional study, we aimed to determine the relationship between sTNF-aR 1 and 2 and measured glomerular filtration rate in patients with T1DM and renal hyperfiltration, defined as directly measured GFR (mGFR)≥120ml/min/1.73m2, compared to those without.

Methods

29 patients with T1DM had mGFR determined using Tc-99m-diethylene-triamine-pentaacetate (DTPA) clearance with Brochner-Mortensen correction. Serum sTNFaR1 and 2 were measured using the Luminex multiplex assay. Difference in sTNFaR1 and R2 values between patients with and without hyperfiltration were then compared.

Results

sTNFR1 and 2 correlated negatively with mGFR (r2 -0.7 and -0.8, respectively, p<0.001). The median mGFR was 124ml/min/1.73m(IQR 121-129) in the hyperfiltration group (n=10) and 94ml/min/1.73m2 (IQR 70-105, n=19) in the non-hyperfiltration group (p<0.0001). Both sTNFaR1 and sTNFaR2 were significantly lower in the hyperfiltration group (sTNFaR1: median 1.2ng/ml (IQR 0.9, 1.4), p=0.006, and sTNFaR2: median 6.1ng/ml (IQR 4.8, 6.7) p=0.0004 ) compared to the non-hyperfiltration group (sTNFaR1: median 1.6ng/ml (IQR 1.4, 2.6) and sTNFaR2: median 8.7ng/ml (IQR 8.0, 10.8), Figure).

Conclusion:

Serum TNFaR1 and 2 are lower in patients with type 1 diabetes and hyperfiltration. These results suggest that inflammatory processes are not associated with the state of hyperfiltration. However, lower levels of these receptors could also be related to their increased clearance in the hyperfiltering state

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