Diabetic nephropathy and proximal tubular damage

Diabetic nephropathy (DN) is a major cause of uremia in developed societies. Inflammation is emerging as an important mechanism for its pathogenesis and progression. Herein, we review 4 recently described cellular receptors that have been shown to mediate diabetic interstitial kidney disease. Peroxisome proliferator-activated receptor-γ attenuates STAT-1 activation and has shown promise in renoprotection. Its clinical utility is limited mainly by fluid retention through upregulation of sodium-hydrogen exchanger-3 and aquaporin-1 channels in the proximal tubule. The bradykinin receptor 2 of the kallikrein-kinin system has been shown to mediate diabetic kidney injury and its blockade conferred renoprotective effects in animal models of DN. The related protease-activated receptor, especially receptor 4, has recently been shown to participate in DN. Further studies are required to confirm its role. Finally, the toll-like receptor, especially TLR4 and TLR2, has been verified in multiple models to be a significant sensor of and reactor to hyperglycemia and other diabetic substrates that orchestrate interstitial inflammation in DN.