Development of in vivo evaluation system of human organic anion transpoter

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In chronic kidney disease (CKD) patients, the accumulation of uremic toxins causes difficulty in controlling blood pressure, impairs renal function and worsens prognosis. The reduction of accumulated uremic toxins protects against the development of hypertension and ongoing renal damage, but there is no established treatment so far. We have demonstrated that the overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly and inflammation in renal failure together with a reduction of plasma uremic toxins, guanidinosuccinate (GSA), asymmetric dimethylarginine (ADMA) and trans-aconitate. Trans-aconitate is a newly identified uremic toxin.By transcriptional analysis, we found that the SLCO4C1 transcription is upregulated by various statins. Statins potentate renal proximal function and facilitate excretion of uremic toxins, resulting preventing hypertension and renal inflammation in the renal failure. These data suggest that SLCO4C1 upregulation provides a novel transporter-based therapeutic strategy for CKD patients to reduce renal damage and life-threatening events.