Impact of Chronic Kidney Disease in Women

Mar 8, 2018 | Newsletter 2018 | 0 comments

Overview

Chronic kidney disease (CKD) is a worldwide public health problem with adverse outcomes of kidney failure and premature death.1 It affects approximately 195 million women worldwide and it is currently the 8th leading cause of death in women, with close to 600,000 deaths each year.2 The risk of developing CKD is at least as high in women as in men and may even be higher.

According to some studies, CKD is more likely to develop in women compared with men, with an average 14% prevalence in women and 12% in men3. In persons with stages 1 to 4 CKD in the US, 15.93 % were women and 13.52% were men in data obtained from the Centers for Disease and Prevention.4

Worldwide the number of women on dialysis is lower than the number of men. At least three(3) major reasons are recognized so far: CKD progression is slower in women compared to men, psycho-socioeconomic barriers such as lower disease awareness lead to late or no start of dialysis among women5 and uneven access to care is a major issue in countries with no universal access to healthcare.

In the report from the Caribbean Renal Registry 2006 which utilized data from patients on long-term renal replacement in Jamaica, there was a male to female ratio of 1.5:1.6

Kidney transplantation is also unequally spread, mostly due to social, cultural and psychological aspects: even in some countries that provide kidney transplantation and equitable treatment for men and women, women tend more often to donate kidneys and are less likely to receive them7. There is indeed a clear need to address issues of equitable healthcare access for women where it is currently lacking and increase awareness and education to facilitate women’s access to treatment and better health outcomes.

 

Obesity and CKD Risk

In a study published in the Journal of the American Society of Nephrology, the risk of CKD was tripled for both men and women who were overweight or obese and ≥ 20 years old.8

Obesity has been found to be higher in females than in males in Jamaica, 12.4% of men vs 37.7% of women being obese.9 Hence, the risk of CKD in women in Jamaica is likely to be higher than that for men.

 

Kidney Diseases in Women

Kidney diseases such as lupus nephritis and acute and chronic pyelonephritis typically affect more women. Urinary tract infections are also more common in women with an increased risk of pregnancy8

 

Lupus Nephritis and Women

Systemic lupus erythematosus is significantly more common in females of child-bearing age. There is a female: male ratio of 8–15:110.This striking predominance in females is thought to be related to endogenous sex hormones which have a complex effect on the immune system. Hence, more females than males will present with lupus nephritis.

Even though different geographic regions have shown that male patients with lupus nephritis had an increased incidence of proteinuria, cellular casts or elevated serum creatinine, this was not associated with an increase in end-stage renal failure or male patients requiring transplantation11

Overall, lupus nephritis remains a major risk factor for morbidity and mortality in SLE despite potent therapies that exist. It still results in CKD or ESRD for too many patients.12

 

Challenges in Women with CKD

Women with CKD face various challenges. These can be grouped as:

  • Menstrual Irregularities
  • Sexual Dysfunction
  • Birth Control
  • Pregnancy
  • Bone Disease
  • Depression

 

Menstrual Irregularities

These are common in women with CKD and include excessive bleeding and missed periods. Women with CKD also enter menopause 3 to 5 years earlier than patients without CKD12.

The tonic release of gonadotropin-releasing hormone (GnRH) regulating basal secretion of the gonadotropins, luteinizing hormone (LH) and FSH appears to remain normal, as CKD progresses.

However, there is the loss of the normal cyclic release of GnRH by the hypothalamus, leading to loss of normal pulsatile gonadotropin secretion by the pituitary and resulting in impaired ovulation13. This can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis.

Treatment with erythropoietin (EPO) has been shown to restore menstrual periods in about 50% of women on dialysis. This is thought to be due to its effect of improving disturbed hormone levels and treating anaemia.14

Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol such as oral contraceptives and postmenopausal hormone therapy on kidney function are more controversial.

Treatment with postmenopausal hormone therapy in women with ESRD has been associated with improved quality of life, bone health, and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease13.

However, large, prospective, randomized studies are needed to evaluate the role of sex hormones in women with kidney disease and the effects on cardiovascular morbidity and mortality.

 

Sexual Dysfunction

This includes loss of libido, fatigue, loss of energy, vaginal dryness, and painful intercourse. Many medications used to treat kidney disease and uremia can cause physical and psychological symptoms that result in a loss of interest in sexual activity.  Adequate dialysis can improve some of these symptoms.

Use of lubricants and vaginal estrogen can be used for dryness and painful intercourse.

 

Birth Control Options

Women with CKD are usually discouraged from using “the pill” as a birth control method due to a greater chance for an increase in blood pressure and DVTs that can complicate their kidney disease15. However, the low estrogen type pill can be used with blood pressure monitoring16

Intrauterine devices and barrier methods such as condoms and diaphragms can also be used.

  

Pregnancy

Women with CKD are less likely to become pregnant than women in the general population. Once the renal function decreases to less than 20 percent of normal (approximately >250µmol/L in a young woman) it is uncommon for women to become pregnant.

Anovulation and miscarriages are very common outcomes in women with CKD and those on dialysis.

Pregnancy also worsens hypertension that is common in women with CKD. They can also have significant worsening of renal function during pregnancy and require dialysis. Studies show that women who perform dialysis for longer durations (more than 24 hours per week) were more likely to have a successful birth12.

In one study performed in the United States, 1.5% of young women on dialysis became pregnant in a two-year period. Half the pregnancies resulted in the birth of a live child. There were many miscarriages in early pregnancy and some stillbirths. All living babies were born prematurely.

It would be best for women on dialysis to use contraceptives than to plan for pregnancy after transplantation where the likelihood of a successful pregnancy rises to 70% over 50% seen in dialysis patients17.

 

Bone Disease in CKD and ESRD

There is a difference among ethnic groups in the relationship of 25-hydroxyvitamin D (25(OH)D) and PTH concentrations with bone mineral density (BMD) and fractures. In the Multi-Ethnic Study of Atherosclerosis (MESA) among 1 773 adult participants, associations of 25(OH)D with BMD were strongest among White and Chinese participants and null among Black and Hispanic participants. Serum PTH was not associated with BMD. Despite considerably lower circulating 25(OH)D levels, Black individuals have substantially higher BMD compared with any other racial/ethnic groups18. 

Worsening renal function has been associated with lower BMD. However, from the Third National Health Assessment and Nutritional Examination Survey (NHANES III) data, there was no significant relationship between decreased BMD and CKD after adjustment for age, sex and race.

Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) publication suggests BMD testing can play a role in screening among the population with stages 3–5 CKD19.

Women with ESRD on dialysis have lower radial and tibial cortical density, higher radial cortical porosity, lower tibial cortical thickness, fewer trabeculae, and greater trabecular separation compared with healthy women. Men with ESRD were found to have only a lower radial cortical density compared with healthy individuals.

High bone turnover was more prevalent in African-American ESRD patients on dialysis than in white patients on dialysis. Also, the African-American patients had a mostly high cancellous bone volume and normal cortical thickness, but high cortical porosity20.

Therefore, there is need to study bone quality and CKD–MBD in patients of varying ethnicities and genders.

Treatment of CKD Metabolic Bone Disease

Existing data support prevention of hyperphosphatemia and associated secondary hyperparathyroidism in CKD. In the absence of hypercalcemia, there is no indication to prescribe phosphate-binders that are less cost-effective than calcium-based agents.

There are also no recommendations about target levels of serum calcium or PTH concentrations that should be achieved to reduce mortality or cardiovascular morbidity in people with CKD

Vitamin D supplements or vitamin D analogs, should not be routinely prescribed in the absence of suspected or documented deficiency, to suppress elevated PTH concentrations in people with CKD, not on dialysis. It is also recommended not to initiate bisphosphonate treatment in people with GFR <30 ml/min/1.73 m2 without a strong clinical rationale21.

 

Depression

Depression is common in all chronic medical illnesses. Women in the general population manifest depression at about twice the rate of men. One in four women on dialysis will screen positive for a depressive illness12.

Patients with CKD who are not on dialysis have rates of depression up to 3 times higher than those in the general population. Also, depression is associated with poor quality of life and increased mortality in patients with CKD and ESRD22.

In patients with ESRD, factors that have been associated with depression include younger age, female gender, white race, longer duration of dialysis, and comorbid conditions such as diabetes, CAD, cerebrovascular disease, and peripheral vascular disease.

Patients with CKD have similar risk factors associated with depression, including younger age, female gender, black race, Hispanic ethnicity, lower education, lower family income, unemployment, hypertension, smoking status, diabetes, and CAD

Since these risk factors occur more often in patients with kidney disease compared with the general population, it is likely that they in part explain the higher prevalence of depression seen in patients with kidney disease compared with the general population23 24.

Non-pharmacologic interventions in Depression

Cognitive behavioral therapy (CBT) has been shown to improve depressive symptoms. The effect of exercise therapy and increased dialysis frequency on depressive symptoms in patients with ESRD has shown mixed results in several trials. A recent review of 4 RCT of exercise interventions in patients with ESRD found exercise improved depressive symptoms in 3 of 4 of the trials. Increased frequency of hemodialysis did not improve depression.

Barriers to treatment of Depression

High pill burden in patients with CKD and ESRD where some patients may not want to add other medication. Also, those patients who accept behavioral therapy may not want to follow recommendations such as home exercises for the therapy to be successful

In addition, nephrologists often do not start therapy for depression in their patients with CKD or ESRD because they believe that this is the responsibility of the primary care provider. This is a major problem for the 65% to 80% of hemodialysis patients who do not have primary care providers. Hence a multidisciplinary approach is needed including psychologists to initiate behavioral therapy22.

 

Conclusion

Women with Chronic Kidney Disease face unique challenges with issues peculiar to their genders such as menstrual irregularities, early menopause, birth control use and pregnancy. They also have a higher burden of lupus nephritis, bone disease, and depression.

A multidisciplinary approach is therefore needed to address these many and complex challenges of women with CKD and ESRD.

 

Written by Dr. Davlyn Dewar MBBS DM (Internal Medicine) International Society of Nephrology Scholar

Secretary, ACPJ

 

Reference:

  1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3: 1–150.
  2. Data on prevalence and mortality in women taken from GBD website: https://vizhub.healthdata.org/gbd-compare/
  3. Global Prevalence of CKD – A Systematic Review and Meta-Analysis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934905/
  4. Centers for Disease Control and Prevention. Age-adjusted prevalence of CKD Stages 1-4 by Gender 1999-2012. Chronic Kidney Disease (CKD) Surveillance Project website. https://nccd.cdc.gov. Accessed December 6, 2016.
  5. Dialysis
  6. Soyibo, AK., Barton, EN Report from the Caribbean Renal Registry 2006 West Indian Med J.2007 Sep;56(4):355-63.
  7. Kidney transplantation
  8. Ejerblad et al Obesity and Risk of Chronic Renal Failure Journal of the American Society of Nephrology June 2006
  9. Wilks, Rainford, Younger Novie, Tulloch-Reid, Marshall et al Jamaica Health and Lifestyle survey 2007-2008
  10. Murphy, Grainne, and Isenberg, David Effect of Gender on Clinical presentation in Systemic Lupus Erythematosus Rheumatology, Volume 52, Issue 12, 1 December 2013, Pages 2108–2115
  11. Almaani, Salem; Meara, Alexa; Rovin, Brad H. Update on Lupus Nephritis CJASN November 2016
  12. Spry, Leslie Women with Chronic Kidney Disease face unique challenges The Blog updated December 6th 2017 https://www.huffingtonpost.com/leslie-spry-MD-facp/women-with-chronic-kidney_b_10163148.html
  13. Ahmed, Sofia B., Ramesh, Sharanya Sex Hormones in Women with Kidney Disease Nephrology Dialysis Transplantation, Volume 31, Issue 11, 1 November 2016, Pages 1787–1795, https://doi.org/10.1093/ndt/gfw084
  14. Periods in Women with Kidney Failure and after Transplantation https://www.kidney.org.uk/help-and-info/medical-information-from-the-nkf-/medical-info-sex-problems-index/medical-info-sex-problems-periods/
  15. Women and Kidney Disease: Focus for World Kidney Day 2018 https://www.kidney.org/newsletter/women-kidney-disease
  16. Contraception https://www.kidney.org.uk/help-and-info/medical-information-from-the-nkf-/medical-info-sex-problems-index/medical-info-sex-problems-common-contraception/
  17. Pregnancy with Kidney failure and on Dialysis https://www.kidney.org.uk/help-and-info/medical-information-from-the-nkf-/medical-info-sex-problems-index/medical-info-sex-problems-pregnancy/
  18. Van Ballegooijen, Adriana J., Robinson-Cohen, Cassianne et al Vitamin D Metabolites and Bone Mineral Density: the Multi-Ethnic Study of Atherosclerosis 2015 Sep; 78: 186–193
  19. Pan, Bo-Lin, Loke, Song-Seng Chronic kidney disease associated with decreased bone mineral density, uric acid, and metabolic syndrome http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190985
  20. Malluche, Hartmut H., Porter, Daniel S. and Pienkowski David Evaluating bone quality in patients with chronic kidney disease Nat Rev Nephrol. 2013 Nov; 9(11):671–680 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018981/
  21. Management of Progression and Complications of CKD Kidney Int Suppl (2011). 2013 Jan; 3(1): 73–90.
  22. Shirazian, Shayan Grant, Candace D. Depression in Chronic Kidney Disease and End-Stage Renal Disease Similarities and Differences in Diagnosis, Epidemiology and Management Kidney Int Rep 2017 Jan; 2(1): 94–107
  23. Nicholas S.B., Kalantar-Zadeh K., Norris K.C. Socioeconomic disparities in chronic kidney disease. Adv Chronic Kidney Dis. 2015;22:6–15. 
  24. Kiberd B. The chronic kidney disease epidemic: stepping back and looking forward. J Am Soc Nephrol. 2006;17:2967–2973.

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