Marcora Mandreoli Antonio Santoro

U.O.C. di Nefrologia, Dialisi ed Ipertensione

Policlinico S.Orsola-Malpighi

Bologna - ITALY

Azienda Ospedaliero-Universitaria

Gender Gender and and

Renal diseasesRenal 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

maschimaschi

maschimaschi

maschimaschimaschimaschi

Cumulative Incidence of End Stage Renal Cumulative Incidence of End Stage Renal DiseaseDisease

USRDS 2007

Numerous studies have indicated that sex hormones affect Mammalian kidneys, causing sexual dimorphism in a variety of morphological and/or functional propertiesBoth 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: 905-913

Gender-dependent effects of aging on the kidney

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Carrero J J et al. Nephrol. Dial. Transplant. 2011;26:270-276

Without T2DM

Without T2DM

with T2DM with T2DM

FF

MM

MM

FF

Cumulative survival of women and men with or withoutDiabetes 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 EffectsSex Steroid Effects

Estradiol Progesterone Testosterone/DHT

Renal Ang II decrease decrease ? increase

AT1 receptors downregulate ? no effect

Endothelin probably decrease ? increase ?

Oxidative stress antioxidant antioxidant pro-oxidant

Vascular effect

    Acute vasodilator vasodilator vasodilator

    Chronic vasodilator vasoconstrictor vasoconstrictor

Sodium reabsorption

? increase increase

How sex steroid may modulate renal injuryHow sex steroid may modulate renal injury

ConclusionsConclusionsScant attention is currently paid to the important biological and psychological differences between men and women with CKDThere is a scarcity of information about the role of menopause in modifying risk profiling and the involvement of sex hormones in the diseaseSex hormones still have a role after menopause and sex specific tissue responses and cellular differences also existFemales 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 functionThe 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.