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Diabetes and its complications have become a public health problem. One of the most important complications is diabetic nephropathy, which is nowadays the main cause of chronic renal failure. In spite of our greater understanding of this complication, the intimate mechanisms leading to the development and progression of renal injury are not well understood. New perspectives in activated innate immunity and inflammation appear to be relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including adipokines, Toll-like receptors, chemokines, adhesion molecules and pro-inflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective leads to important therapeutic considerations, with new pathogenic pathways becoming important therapeutic targets that can be translated into clinical treatments for diabetic nephropathy.

Background: Recent studies have shown a role for inflammation in the pathogenesis of diabetic nephropathy (DN). Tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 are cytokines with a prevalent pro-inflammatory activity. Our objective was to study the renal gene expression of TNF-α, IL-1 and IL-6 in DN and their relationship with renal damage assessed by urinary albumin excretion (UAE). In addition, we also investigated the effect of angiotensin-converting enzyme inhibition and pentoxifylline (PTF) administration on these parameters. Methods: After streptozotocin-induced diabetes, rats received either no treatment or therapy with enalapril (EN) or PTF for 8 weeks. Renal expression of pro-inflammatory cytokines was evaluated by real-time polymerase chain reaction. Urinary cytokine excretion and albuminuria were also evaluated. Results: Renal cortical mRNA expression for TNF-α, IL-1 and IL-6 in untreated diabetic rats was 2.4-, 1.2- and 3.4-fold higher than in non-diabetic rats. Kidney weight and UAE were significantly associated with renal mRNA expression of TNF-α and IL-6. Both EN and PTF administration virtually abrogated the overexpression of TNF-α, IL-1 and IL-6, which was associated with a reduction in kidney weight and urinary albumin excretion. Conclusion: The renal expression of the main pro-inflammatory cytokines TNF-α, IL-1 and IL-6 is increased in DN, which is significantly associated with UAE. EN and PTF administration prevented this enhanced expression, leading to a decrease in urinary cytokine excretion and a reduction in albuminuria. These findings provide novel insight into the pathogenic mechanisms of DN, supporting the hypothesis that inflammatory mechanisms play a role in the renal injury secondary to diabetes mellitus.

No abstract

Diabetic nephropathy has become the main cause of renal failure, but unfortunately the intimate mechanisms leading to the development and progression of renal injury are not yet fully known. Activated innate immunity and inflammation are relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including chemokines, adhesion molecules, and proinflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective leads to important therapeutic considerations, with new pathogenic pathways becoming important therapeutic targets that can be translated into clinical treatments for diabetic nephropathy.

No abstract

In patients with type 2 diabetes, urinary TNFalpha excretion is elevated and correlates with severity of renal disease in terms of both glomerular and tubulointerstitial damage, suggesting a significant role for TNFalpha in the pathogenesis and progression of renal injury in diabetes mellitus.

DN was associated with increased renal expression of TNF-alpha and UAE. Enalapril administration prevented this enhanced expression of TNF-alpha and decreased urinary cytokine excretion and albuminuria. These data provide a novel insight into the pathogenic mechanisms of DN, and support the hypothesis that inflammatory mechanisms may play a significant role in the development and progression of renal injury secondary to diabetes mellitus.