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Drugs currently being investigated for treatment of diabetic kidney disease
There are multiple other therapies currently being investigated for treatment of diabetic kidney disease.
Further studies are needed for all of the following agents before these agents can be recommended for treatment of diabetic kidney disease.
Endothelin A Receptor Antagonists
The endothelin system plays an important role in the pathogenesis of DKD. Endothelin receptor 1 stimulation increases renal vasoconstriction, extracellular matrix accumulation, and interstitial fibrosis.
Endothelin A receptor antagonists have shown promise in the treatment of DKD, along with the use of ACE inhibitors in animal studies.
Human trials are ongoing; however, one clinical trial studying avosentan was terminated early due to increased cardiovascular events of fluid overload and congestive heart failure. Another endothelin antagonist, atrasentan, was shown to reduce proteinuria in a short study. Longer and larger trials are in progress.
Phosphodiesterase Inhibitors
Phosphodiesterase inhibitors block inflammatory cytokines and leukotrienes associated with DM. They might also play a role in augmenting glomerular hypertrophy occurring in DM.
Small studies suggest that phosphodiesterase inhibitors can slow the rate of eGFR decline in DKD. However, large randomized multicenter studies have not been performed.
Mineralocorticoid Antagonists (MRAs)
MRAs reduce proteinuria when used alone and have an additive effect when used with an ACE inhibitor or ARB in the treatment of DKD.
There are no long-term data evaluating the benefit of adding an MRA to an ACE inhibitor or ARB on hard kidney outcomes such as slowing loss of eGFR and preventing ESRD. Furthermore, worsening hyperkalemia by combining these agents may limit the usefulness of MRAs.
Transforming Growth Factor- β (TGF- β ) Inhibitors
The role of TGF-β–induced mesangial matrix expansion and tubular fibrosis in DKD is well established. Early human trials have found a significant increase in eGFR in individuals with DKD treated with TGF-β inhibitors.
Selective Serotonin Receptor Antagonists
Serotonin is a proinflammatory mediator released by activated platelets. Stimulation of the Serotonin receptors is associated with mesangial proliferation, increased type IV collagen deposition, platelet aggregation, and regulation of tissue vasculature.
Serotonin receptor subtype 2A (5-HT2A) is found on mesangial cells and is believed to play a role in DKD. Small studies have shown that 5-HT2A antagonists decrease albuminuria in humans with DKD.
