Marcora Mandreoli Antonio Santoro U.O.C. di Nefrologia, Dialisi ed Ipertensione Policlinico S.Orsola-Malpighi Bologna - ITALY Azienda Ospedaliero-Universitaria Genderand Renal diseases

- The incidence of CKD is major in man than in women - Renal disease in women with polycystic kidney disease, IgA nephropathy, membranous glomerulopathy, and ‘chronic renal disease of unknown aetiology’ progresses at a slower rate than it does in blood pressure- and lipid levels-matched men with these diseases - CKD patients behave differently from the general population, lacking a female survival advantage during renal replacement therapy. Impact of gender on the incidence and progression rate of Chronic Kidney Disease (CKD) J Neugarten. J Am Soc Nephrol 11:319, 2000

Neugarten J. JASN 2000; 11: 319 maschi

Cumulative Incidence of End Stage Renal Disease USRDS 2007

Numerous studies have indicated that sex hormones affect Mammalian kidneys, causing sexual dimorphism in a variety of morphological and/or functional properties Both α- and β-estrogen receptors (ERα and ERβ) have been detected in the kidney, and specifically in mesangial cells. Studies in vascular tissue, studies of cultured male renal mesangial cells have shown that estradiol suppresses collagen synthesis and stimulates metalloproteinase activity via activation of estrogen receptors

Silbiger SR Kidney International (2011) 79, 382–384 Effects of sex hormones Haemodinamic pathway

A.L. Gava,et al. Braz J Med Biol Res 2011; 44: Gender-dependent effects of aging on the kidney + --

Carrero J J et al. Nephrol. Dial. Transplant. 2011;26: Without T2DM with T2DM F F M M M M F F Cumulative survival of women and men with or without Diabetes 5 years after the start of dialysis

"Reduced levels of estrogen and imbalance in the expression of estrogen receptors is one of the contributing mechanisms for the loss of the female sex as a protective factor in diabetes "Estrogen is renoprotective by attenuating the decline in renal function and preventing renal pathology associated with diabetic nephropathy Hypothesis

Estrogen receptors in the kidney

Estrogen attenuates renal structural damage in diabetic nephropathy

Estrogen attenuates the decline in renal function in diabetic nephropathy

Mechanisms Sex Steroid Effects EstradiolProgesteroneTestosterone/DHT Renal Ang IIdecreasedecrease ?increase AT 1 receptorsdownregulate?no effect Endothelinprobably decrease?increase ? Oxidative stressantioxidant pro-oxidant Vascular effect Acute vasodilator Chronic vasodilatorvasoconstrictor Sodium reabsorption ?increase How sex steroid may modulate renal injury

Conclusions Scant attention is currently paid to the important biological and psychological differences between men and women with CKD There is a scarcity of information about the role of menopause in modifying risk profiling and the involvement of sex hormones in the disease Sex hormones still have a role after menopause and sex specific tissue responses and cellular differences also exist Females develop less age-dependent loss of renal function, in part because of cardiorenal protective effects of estrogens, but estrogen acts via multiple pathways, not all of which are beneficial for renal function The true role of sex hormones in conditioning the CKD progression is not completely clear: most probably they don’t have a direct causal role, but they act as permissive factors.