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Explore the impact of chronic kidney disease on women in emerging economies, emphasizing hormonal differences, pregnancy implications, and the prevalence of renal issues. Uncover the reasons for slower CKD progression in females and the risks associated with pregnancy-related kidney complications.
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Women and kidney health in emerging countries Dr Manisha Sahay Professor and Head Nephrology Osmania Medical college and hospital Hyderabad
Eighth leading cause of death among women. 600,000 women die every year from Chronic Kidney disease Chronic kidney disease affects 195 million women worldwide
Nature protects women • Women bring life into the world • In the general population women have a longer life expectancy than men • prevalence of cardiovascular risk factors and events in women • Murray, Global Burden of disease, Lancet ,1997 • Increases risk post menopausal
Anatomic differences • Kidneys smaller and lighter • 300 gmvs 350 gm • Have a 15% lower GFR
Physiological differences Females Estrogen Protective Testosterone less protection Different actions of hormones on transporters in the kidneys Drug effects and toxicities
Testosterone Male hormone • Promotes apoptosis of proximal tubule cells - Verzola, BBRC, 2009 • Testosterone NO • Ahmed et al, CJASN,2007 • Carrero, Curr opinion in H, 2010 • Estrogens have • anti-fibrotic • anti-apoptotic effects • NO syntheis • anti inflammatory • Inhibits RAS • Stringer, KI, 2005 • Elliot KI 2007 Nature protects Females • Interaction of hormones with specific kidney receptors • -Sandberg, Gend Medicine, 2008
Proteinuria less in females • Estrogen reduces proteinuria • Oral contraceptive use associated with macroalbuminuria • Ahmed Diabetes care, 2005 • Type-2 diabetic proteinuric hypertensive women who received HRT had proteinuria & creatinine clearance • Agarwal, M, AJKD,2005
Chronic kidney disease less in females • CKD Males: females 70:30 • (hospital based registry) • Rajapurkar, BMC, 2012 • CKD Bangladesh M:F 1.2:1 • Mahmud Hasan, CBMJ, 2012 • CKD Pakistan 1:1 • Ullah, SJKDT, 2015
Glomerular disease- biopsy 10 year data Osmania Men 1717 Women 1279
CKD progression slightly less in women • Men were associated with a worse CKD progression • Evans, AJKD, 2005, Eriksen, KI, 2006 • In 840 non-diabetics, loss of renal function slower in women esp if younger and premenopausal • Coggins, NDT,1998 • NeugartenJ,. JASN, 2000;Eriksen, KI, 2006 • Seliger. Gender & renal disease. CurrOpinNephrolHypertens 2001 • ADPKD, IgA, MN, and ‘CKDu’ progress at a slower rate than it does in BP- and lipid levels-matched men • Neugarten et al, JASN, 2000 • No difference males and females –post menopausal • Jafar, NDT, 2000
Thus most incidence and prevalance of diseases seems to be less in women and progression to CKD slower in females
What makes a woman different from man??Men are from MarsWomen are from Venus!!
Pregnancy • Women face additional risks to their kidney health, specifically during pregnancy • Global Burden of Diseases website. Data on Chronic Kidney Disease prevalence and mortality in women. Available from: https://vizhub.healthdata.org/gbd-compare/ • Pregnancy is a major stressor • Normal pregnancy does not harm the mother • Pregnancy if complicated or pregnancy in CKD women detrimental
Pregnancy AKI in emerging countries 30 times more common in merging countries Swati Rao, KI reports, 2016
Renal failure In pregnancy Developed/emerging countries PET Poor Septic abortion Sepsis Bangladesh, 2012 • Early pregnancy AKI • Septic abortion • Later pregnancy AKI • Preeclampsia (PE)/HT • 3% women • Piccoli , J Nephrology, 2011 • Ante partum hemorrhage • Post partum hemorrhage • Puerperal sepsis • Acute fatty liver of pregnancy • HUS
PET (High BP in pregnancy) Most important cause of renal failure • PET is the commonest glomerular disease in the world • 3-10% of all pregnancies • Liz Livingstone, KI reports, 2018
placental dysfunction damages kidneys CKD cause placental dysfunction Impaired Angiogenesis,Vassoconstritcion, oxidant stress, inflammation
PET • Maternal deaths • 76,000 maternal deaths worldwide / year • 16% of maternal deaths in LMICs • Endecclapsia.org • 3-4X risk of stroke & heart disease • Munkhaugen, NDT,2009 • Agatha, J Nephr, 2017 • Kidney failure • 4 to 5 times more likely to develop kidney failure
PET causes CKD in women • PE is a risk factor for the future development of CKD and ESRD in the mother. • Mol, Lancet, 2016 • podocyteloss is a hallmark of PE, suggesting permanent glomerular damage • Garovic, CJASN,2014 • Endotheliosismay herald glomerulosclerosis • tubular and vascular damage may coexist • Shiki, AJN,1990 • Cortical necrosis dreaded outcome
Healthy pregnant female becomes dialysis dependent CKD 105 cases over 7 years 39% obstetric causes of cortical necrosis
PET does not spare the child • Babies born to mothers with preeclampsia may • May not be born at all (Intrauterine death) • preterm • low birth weight/small for gestational age • Have increased risk of kidney disease • low nephron number , increased risk of CKD, high BP later in life • Fizpatrick, Int Journal of women’s health, 2016
Systemic lupus erythematosus • Affects women (9:1 F:M) in reproductive yrs. • Immunomodulatory effects of estrogen make SLE common in females • SLE affects kidneys in 50% • ESKD-10% • major risk factor for morbidity and mortality • Poor Pregnancy outcomes • PET 7.6% • APLA worsens prognosis • Fetal heart blocks if SSA/SSB • Treatment is also toxic - infertility
DKD in women • DKD prevalence more in men • Luk, Diabetes care 2008, Ohta, Diabetes med 2010] • DKD risk factors more in women ie obesity and hypertension • Older Women with diabetes have an increased prevalence of advanced DKD • Margaret, AJN, 2012 (Pathways study) • McFarlane, Jr Clinical hypetension, 2005
Obesity and kidney disease • 24.9% of CKD in women is associated with overweight and obesity vs 13.8% in men • Wang, KI, 2008 • prevalence of obesity • 49%, 57%in females • abdominal obesity • 63% women • 48% men • ICKD, GI, 2017
Urinary tract infections Frequent in women Recurrent UTI common Pregnancy UTI may become complicated Important to rule out underlying cause esp in girls Treatment of pregnancy UTI important
So we have understood… Kidney disease generally less Pregnancy UTI SLE DM Obesity
What about treatment for renal disease?Dialysistransplantation
Less Women on dialysisacross all economies.. • Our study from India 73% patients on dialysis are men • Maaz Sheikh, VJ, Manisha Sahay et al. KI 2018 • Nationwide survey of ESRD by Japanese Society for Dialysis therapy revealed a higher incidence and prevalence in men • KunitoshiAsaki, KI, 2008 • Studies in Africa show that men were more likely to receive RRT than women • Halle, BMC, 2015 • US study reports women having a significantly higher odds ratio of 1.70 for late initiation of dialysis compared to men • Kausz, JASN 2000
Why less dialysis in females? ?? ESRD less common in females Less females seek medical attention Less females receive medical attention
CENTRE OSMANIA HOSPITAL3000 dialysis per month1008 forfemales
Peritoneal dialysis in females • ed risk of encapsulating peritoneal sclerosis (EPS) in women undergoing peritoneal dialysis • EPS have shown improvement with tamoxifentherapy, an antiestrogen compound . • Weisinger JR Kidney Int 2000 • Hernandez EKidneyInt 2003
Universal truth..All emerging countries.. Women donate Men receive
All across the world …. • US, France, China, India, Pakistan, Srilanka • ( Transplant rates lower in women than men) • Less women registered on national transplant waiting lists • Mothers are more likely to be donors, as are female spouses • Couchod, Tx 2012 • Liu, ClinTx 2013 • Saran AJKD 2017
Osmania data 700 live related transplants 85% donors females 87% recipients males Mothers, sisters, spouses
Even girl child at disadvantage… Survey from 35 countries participating in European Society for Pediatric Nephrology/European Renal Association- European Dialysis and Transplant Association Registry reported that girls had a lower access to renal transplantation than boys • Hogan AJT 2016
Is female kidney better?
Are female kidneys better? • Lower number of nephrons • express more HLA antigens and are more antigenic • Zeier M,. J Am SocNephrol. 2002 • more susceptible to nephrotoxic effects of immunosuppressants • Shibue T, Clin Transplant. 1987 • Female donor kidneys have a worse 5-year survival • Głyda M, Pol PrzeglChir. 2011 • Shibue T, ClinTransplant. 1987