Tumor necrosis factor receptor 2 involved in renal decline in diabetes

By Sally Robertson, B.Sc.Feb 8 2013

Researchers have found that circulating levels of tumor necrosis factor receptor 2 (TNF-R2) are independently associated with the development of chronic kidney disease (CKD) in nonobese Japanese patients with Type 2 diabetes.

Mitsuo Fukushima (Okayama Prefectural University, Japan) and colleagues say the association is "intriguing to consider."

Chronic inflammation is assumed to be one of the primary risk factors associated with atherosclerosis and renal dysfunction in patients with Type 2 diabetes. Yet, "a major problem is that obesity per se is both associated with low grade inflammation and the development of CKD in patients with Type 2 diabetes," says the team.

In the current study, the researchers examined the relationship between inflammatory biomarkers and other variables and the presence of CKD in 106 nonobese patients who had a mean body mass index of 22.2 kg/m² and a mean diabetes duration of 11.5 years.

The team found that patients who had an impaired estimated glomerular filtration rate (eGFR) (<60 mL/min per 1.73 m², stage 3 CKD) had a significantly longer mean diabetes duration and significantly higher levels of triglycerides, urinary albumin, and log TNF-α, soluble TNF-R1 (sTNF-R1), and sTNF-R2 than those with normal eGFR (≥60mL/min per 1.73 m²). Reduced eGFR was not associated with changes in adiponectin, leptin, or high-sensitivity C-reactive protein.

As reported in Diabetes Research and Clinical Practice, multivariate analysis showed that sTNF-R2 was the only inflammatory marker that was significantly associated with the development of stage 3 CKD in the patients.

"Thus, it may be suggested that increased TNF system activity is associated, independent of age, body weight, glucose concentration, insulin resistance, or adipocytokine, with development of stage 3 CKD among non-obese patients with type 2 diabetes," write Fukushima and team.

Although the mechanism by which elevated sTNF receptors may be connected to renal injury in patients with diabetes is unclear, TNF system activity may be involved in the deterioration of kidney function, say the authors. "The exposure of the kidney to TNF-α has been shown to increase [messenger] RNA expression of TNF receptors in renal tubulointerstitium and trigger cell death."

"Further studies are needed to characterize the role of TNF system activity on impaired renal function and atherosclerosis in the Japanese population," they conclude.

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