Friday, February 5, 2010

JOURNAL CLUB: Pirfenidone Is Renoprotective in Diabetic Kidney Disease

Past Journal Club we discussed the potential effect of Pirfenidone(PFD) in halting the progression of Diabetic nephropathy. this paper was published in Jasn April 2009.
Characteristic morphologic lesions of DN include glomerular hypertrophy, thickening of the basement membrane, and mesangial expansion. Several interventions, such as tight glycemic control and antihypertensive therapy, especially angiotensin converting enzyme inhibitors (ACEIs) and angiotensinII receptor blockers, have been shown to slow the progression of established disease. Nevertheless,DN remains a major long-term complication of both types 1 and 2 diabetes. the mechanism of DN is multi factorial as we know. inflammation,fibrosis, hemodynamic effects both in the mesangial cells and matrix as well as as in the podocytes, are some elements which are involved in this very complex cascades of disease process. and this study tried to examine the possible benefits of PFD in halting the progression of DN through inhibiting TGF-B production and therefore antifibrotic and possibly anti-inflammatory effects. Pirfenidone (PFD; 5-methyl-1-phenyl-2-(1H)-pyridone) is
a low molecular weight synthetic molecule that exerts dramatic antifibrotic properties in cell culture and various animal models of fibrosis. it has been shown to improve pulmonary function tests in patient with IPF post Lung transplantation.
To explore the therapeutic potential of PFD, we administered PFD to 17-wk-old db/db mice for 4 wk. PFD treatment significantly reduced mesangial matrix expansion and expression of renal matrix genes but did not affect albuminuria.
the idea is intriguing because it opens up the possibly of treating this disease through different mechanisms. however, this study although shows that PFD did decrease the production of TGF-B, it did so in cell cultures and only mesangial cells were involved. Also there was no clinical parameters such as BP, and GFR. and more importantly there was more protinuruia in the PFD treated mice. and this is obliviously not a welcome effect.
SO we would want more studies, preferably in the Podocytes. as well clinical outcomes.
for the complete article go to J Am Soc Nephrol 20: 1765–1775, 2009. ISSN : 1046-6673/2008-1765.
posted by Ezra Hazzan MD on feb 5, 2010.

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