Urinary TNF-α and NGAL are correlated with the progression of nephropathy in patients with type 2 diabetes

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Abstract

The aim of this study was to investigate the correlation of the proinflammatory marker tumor necrosis factor-α (TNF-α) and the tubular marker neutrophil gelatinase-associated lipocalin (NGAL) with the progression of the early stage of type 2 diabetic nephropathy (DN). Baseline levels of urinary TNF-α and NGAL were measured in 63 non-diabetic controls and 201 patients with type 2 diabetes and different albuminuria statuses. The patients with diabetes (n=125) with normo- or microalbuminuria were subsequently followed-up for 28 (25-32) months, with routine measurements of creatinine and urinary albumin excretion (UAE). It was observed that baseline levels of urinary TNF-α and NGAL were significantly elevated and correlated with the severity of albuminuria in patients with diabetes. During the follow-up, the urinary levels of TNF-α and NGAL were observed to be significantly correlated with a rapid decline in the estimated glomerular filtration rate (eGFR). Following adjustment for other progression promoters, including albuminuria, TNF-α remained a significant predictor of eGFR decline. These results suggest that inflammation is important in the pathogenesis of DN and indicate that TNF-α may be used as an independent predictor for the progression of DN at the early stage.

Figures

  • Table I. Baseline characteristics of controls and patients with type 2 diabetes, stratified according to albuminuria status.
  • Table II. Multiple linear regression analyses of u-ACR as a dependent variable in patients with type 2 diabetes.
  • Figure 1. (A) Box plot graph of urine TNF-α/urine creatinine (u‑TCR) measured in controls and patients with diabetes, stratified according to albuminuria status. (B) Box plot graph of urine NGAL/urine creatinine (u‑NCR) measured in controls and patients with diabetes, stratified according to albuminuria status. (C) Correlation between urine albumin/urine creatinine (u-ACR) and u-TCR in patients with diabetes. (D) Correlation between u-ACR and u-NCR in patients with diabetes. Logarithm-transformed values were used for single regression analysis.
  • Table III. Multiple linear regression analyses of the annual decline in eGFR as a dependent variable in patients with type 2 diabetes.
  • Figure 2. Cumulative percentage of patients with diabetes, allowing for different cut-offs of annual decline in estimated glomerular filtration rate (eGFR), in three groups stratified according to their baseline levels of (A) urine TNF‑α/urine creatinine (u-TCR) or (B) urine NGAL/urine creatinine (u-NCR), respectively. Protein levels are lowest in tertile 1 and highest in tertile 3. (C) Mean baseline levels of u-TCR and u-NCR in different tertiles.

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APA

Wu, J., Ding, Y., Zhu, C., Shao, X., Xie, X., Lu, K., & Wang, R. (2013). Urinary TNF-α and NGAL are correlated with the progression of nephropathy in patients with type 2 diabetes. Experimental and Therapeutic Medicine, 6(6), 1482–1488. https://doi.org/10.3892/etm.2013.1315

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