Int J Med Sci 2020; 17(14):2113-2124. doi:10.7150/ijms.46259

Research Paper

Serum transferrin predicts end-stage Renal Disease in Type 2 Diabetes Mellitus patients

Lijun Zhao1,2, Yutong Zou1, Junlin Zhang1, Rui Zhang1, Honghong Ren1, Lin Li3, Ruikun Guo1, Jie Zhang4, Fang Liu1✉

1. Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
2. Division of General Practice, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
3. Division of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
4. Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, Chengdu China.

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Citation:
Zhao L, Zou Y, Zhang J, Zhang R, Ren H, Li L, Guo R, Zhang J, Liu F. Serum transferrin predicts end-stage Renal Disease in Type 2 Diabetes Mellitus patients. Int J Med Sci 2020; 17(14):2113-2124. doi:10.7150/ijms.46259. Available from http://www.medsci.org/v17p2113.htm

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Abstract

Background: To investigate the relationship between serum iron status and renal outcome in patients with type 2 diabetes mellitus (T2DM).

Methods: Chinese patients (n=111) with T2DM and biopsy-proven diabetic nephropathy (DN) were surveyed in a longitudinal, retrospective study. Serum iron, total iron-binding capacity, ferritin, and transferrin were measured at the time of renal biopsy. Iron deposition and transferrin staining were performed with renal biopsy specimens of DN patients and potential kidney donors. End-stage renal disease (ESRD) was the end-point. ESRD was defined as an estimated glomerular filtration rate <15 mL/min/1.73 m2 or the need for chronic renal replacement therapy. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for the influence of serum iron metabolism on ESRD.

Results: During a median follow up of 30.9 months, 66 (59.5%) patients progressed to ESRD. After adjusting for age, sex, baseline systolic blood pressure, renal functions, hemoglobin, HbA1c, and pathological findings, lower serum transferrin concentrations were significantly associated with higher ESRD in multivariate models. Compared with patients in the highest transferrin quartile (≥1.65 g/L), patients in the lowest quartile (≤1.15 g/L) had multivariable-adjusted HR (95% confidence interval) of 7.36 (1.40-38.65) for ESRD. Moreover, tubular epithelial cells in DN exhibited a higher deposition of iron and transferrin expression compared with healthy controls.

Conclusions: Low serum transferrin concentration was associated with diabetic ESRD in patients with T2DM. Free iron nephrotoxicity and poor nutritional status with accumulated iron or transferrin deposition might contribute to ESRD.

Keywords: diabetic nephropathy, end-stage renal disease, transferrin, iron nephrotoxicity