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A Journal on Nephrology and Urology

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Minerva Urologica e Nefrologica 2004 March;56(1):1-14

language: English, Italian

Gender and the progression of chronic renal diseases: does apoptosis make the difference?

Gandolfo M. T. 1, Verzola D. 1, Salvatore F. 1, Gianiorio G. 1, Procopio V. 1, Romagnoli A. 2, Giannoni M. 1, Garibotto G. 1

1 Nephrology Division Department of Internal Medicine University of Genoa, Genoa, Italy
2 Urology Division University of Genoa, Genoa, Italy


Several stud­ies in pa­tients ­with chron­ic kid­ney dis­eas­es ­have ­shown ­that men ­have a ­more rap­id dis­ease pro­gres­sion ­than wom­en. Also, ­with age­ing, men ex­hib­it great­er decre­ments in re­nal func­tion and in­creased glo­mer­u­lar scler­o­sis ­than wom­en. Data ­from ­meta-anal­y­sis stud­ies in­di­cate ­that wom­en ­with sev­er­al non-di­a­bet­ic re­nal dis­eas­es ­such as mem­bra­nous neph­rop­a­thy, IgA neph­rop­a­thy and poly­cys­tic kid­ney dis­ease ­present a slow­er pro­gres­sion, but in di­a­bet­ic re­nal dis­ease ­this is not yet es­tab­lished. Thus, men ap­pear to be at great­er ­risk for re­nal in­ju­ry ­than are wom­en, but the under­ly­ing mech­a­nisms are un­known. Sex hor­mones may me­di­ate the ef­fects of gen­der on chron­ic re­nal dis­ease, ­through the inter­ac­tion ­with the re­nin-an­gio­ten­sin ­system, the mod­ula­tion of ni­tric ox­ide syn­the­sis and the down­reg­u­la­tion of col­la­gen deg­ra­da­tion. New ob­ser­va­tions in­di­cate ­that an­dro­gens may con­trib­ute to con­tin­u­ous ­loss of kid­ney ­cells ­though the stim­u­la­tion of ap­op­tot­ic path­ways. Apoptosis is an ­unique ­type of pro­grammed ­cell ­death ­which is ac­ti­vat­ed in sev­er­al chron­ic kid­ney dis­eas­es. Studies in vi­tro in­di­cate ­that an­dro­gens ­prime a Fas/FasL de­pen­dent ap­op­tot­ic path­way in kid­ney tu­bule ­cells. This ap­op­tot­ic ­cell ­death path­way is re­cep­tor-­linked and inter­acts ­with the mith­o­chon­dri­al path­way, ­which may be ac­ti­vat­ed by oth­er mech­a­nisms, ­such as tox­ins and is­che­mia. Therefore, the mech­a­nisms to ­cell ­death ­which are ­primed by an­dro­gens may inter­act ­with oth­ers oc­cur­ing in sev­er­al con­di­tions lead­ing to the ­loss of re­nal ­cells. These find­ings are con­sis­tent ­with a ­role for an­dro­gens to pro­mote chron­ic re­nal in­ju­ry in men.

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