Urinary and renal interstitial concentrations of TNF-α increase prior to the rise in albuminuria in diabetic rats

Urinary and renal interstitial concentrations of TNF-α increase prior to the rise in albuminuria in diabetic rats.BackgroundThe development of diabetic nephropathy has been linked to the release of vasoactive hormones and growth factors. Currently the role of inflammatory cytokines in this pathogenic process is not clear.MethodsWe utilized the microdialysis technique to monitor early changes in tumor necrosis-α (TNF-α) levels in the renal interstitial fluid and urine of conscious Sprague-Dawley rats (N = 8) before and after induction of diabetes with streptozotocin (STZ). Measurement of the urinary albumin excretion (UAE) was utilized to monitor the development and progression of diabetic nephropathy.ResultsUAE increased from 0.56 ± 0.20 μg/min to 8.14 ± 2.98 μg/min 17 days after induction of diabetes (P = 0.01). Renal interstitial fluid TNF-α increased from 11.96 ± 5.32 pg/mL at baseline to 45.02 ± 11.69 pg/mL 5 days after induction of diabetes (P = 0.03). Renal interstitial fluid TNF-α levels remained elevated throughout the remainder of the study period. Urinary TNF-α also increased significantly compared to baseline 3 days after induction of diabetes (294.18 ± 36.94 pg/mL vs. 16.05 ± 6.07 pg/mL, P < 0.002). There was a second significant rise in urinary TNF-α concentration to 638.16 ± 36.94 pg/mL 21 days after induction of diabetes (P < 0.001). Serum TNF-α levels were undetectable before STZ injection and remained undetectable by the end of the study. Urinary and renal interstitial fluid TNF-α in the control rats (N = 5) did not change throughout the study.ConclusionWe found an early rise in renal TNF-α levels after induction of diabetes with STZ, which precedes the rise in UAE by about 2 weeks. These findings suggest a possible contribution of TNF-α in the complicated pathogenic process resulting in microalbuminuria in diabetes.