Update on role of direct renin inhibitor in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renin-angiotensin-aldosterone system (RAAS) plays a critical role in the development of DKD with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) being the mainstay of treatment. Systemic RAAS activity has been implicated in the pathogenesis of DKD, but lately interest has shifted to intrarenal RAAS effect. With the discovery of the (pro)renin receptor and ACE independent pathways of angiotensin II production, our understanding of role of renin in end organ damage has improved significantly. SUMMARY: We summarize our current understanding of ACE dependent and independent pathways in the development of DKD and the preclinical models demonstrating renal effects of direct renin inhibitors (DRIs). We then review clinical studies and trials performed so far evaluating the efficacy of aliskiren on renal outcomes and safety in DKD. KEY MESSAGE: At present, there is little evidence for renal benefit of aliskiren in DKD beyond that offered by ACEIs or ARBs. Combining aliskiren with ACEI or ARB in DKD did not significantly improve renal outcomes in comparison with ACEI or ARB monotherapy in clinical trials. Slightly more adverse events including hyperkalemia, acute kidney injury and hypotension were observed in the combination therapy as compared to the monotherapy. Thus, current evidence suggests that aliskiren, because of its antihypertensive and antiproteinuric effects, maybe used as monotherapy in DKD and considered an equivalent alternative to ACEIs or ARBs. Careful monitoring for renal adverse effects would allow safe clinical use of DRI.

Structure-based analysis of curcumin and conventionaldrugs targeting tumor-inducing protein PHF20.

Recently, the PHF20 has been reported as tumor inducer protein by suppressing the activity of tumor suppressor protein p53. Conventional drugs (albendazole, doxazosin, and propranolol) are used for treatment of cancer causing side effect. The secondary metabolite curcumin is employed in various diseases treatment including cancer. The present study is to explore curcumin in comparison to selected conventional drugs by using molecular docking. The online database "Molinspiration online server" detected the physicochemical pharmacokinetics and drug likeness score of curcumin and conventional drugs. Results from Molinspiration online server showed that curcumin did not violate the "Lipinski five rule" for drug. The lead compound for molecular docking exhibited the potential interaction to the active site of PHF20. The resulted binding energy of albendazole and doxazosin were -21.97 and -26.64 respectively. The binding energy (-18.12 kcal/mol) of curcumin was higher than propranolol (17.62 kcal/mol). Thus, curumin has greater potential to interact for further consideration as an anti-cancerous regimen.