Emerging treatments
Combination of aldosterone receptor blockade
Several small studies have suggested a beneficial effect of the combination of aldosterone blockade with blockade of the renin-angiotensin system on proteinuria.[58] In one of these studies, five patients with Alport syndrome were enrolled.[59] Urinary protein to creatinine ratio was reduced at 3, 6, 12, and 18 months, while estimated glomerular filtration rate did not change. A drop in systolic and diastolic blood pressure was statistically significant, and serum potassium level was slightly elevated. None of the patients showed signs of severe hyperkalemia (>5.0 mEq/L). The results of these studies suggest that aldosterone receptor blockade combined with ACE inhibitors and angiotensin-II receptor antagonists could offer a valuable adjuvant treatment for the reduction of proteinuria in patients with Alport syndrome, as in those with other chronic kidney diseases.[5]
Cyclosporine
One small study has suggested that the nephrotoxicity of cyclosporine is likely to outweigh its potential therapeutic benefit in reducing proteinuria.[60] After a 6-month period, mean proteinuria decreased from 2±1.06 g/day to 0.65±0.73 g/day, and mean albuminemia had increased from 29±5.2 g/L to 35±6.5 g/L. Mean inulin clearance decreased from 102±29 mL/minute/1.73 m² to 74±16.3 mL/minute/1.73 m².
Bardoxolone methyl
Bardoxolone methyl is an activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling.[61] The Food and Drug Administration (FDA) did not assess the phase 3 trial results as positive and voted not to approve this drug.[44] An application to European Medicines Agency (EMA) for a marketing authorization was withdrawn as the EMA considered that the data provided did not allow a conclusion on a positive benefit-risk balance.
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