• Chronic kidney disease (CKD) affects one in 10 women globally and remains underdiagnosed and undertreated.
• More research on the impact of CKD therapies in women is needed.
• Reproductive health also plays key role.

Kidney disease in women may be often underdiagnosed and undertreated due to lack of sex-specific research and recognition of reproductive health as an important variable, according to a scientific statement published in Circulation.

The American Heart Association issued a scientific statement calling on greater recognition and treatment of kidney disease in women; assessment of reproductive health during kidney care; and increased enrollment of women in clinical trials to improve knowledge of sex-specific treatment outcomes.

The authors reported that approximately one in 10 women globally have chronic kidney disease (CKD), and women with CKD often go undiagnosed for a variety of reasons.

One example cited in the statement was that based on the 2021 CKD-EPI creatinine equation for estimated glomerular filtration rate (eGFR), a creatinine level of 1 mg/dL in a 50-year-old man indicates an eGFR of 92 mL/min/1.73 m²; however, similar levels for a women the same age is indicative of an eGFR of 69 mL/min/1.73 m², or stage 2 CKD.

“One important challenge is that kidney disease may be underrecognized in women. Kidney function is commonly estimated using creatinine, a waste product generated by muscle,” Eman Y. Gohar, PhD, MS, FAHA, assistant professor of medicine in the division of nephrology and hypertension at Vanderbilt University Medical Center in Nashville, Tennessee, and chair of the scientific statement writing group, told Healio. “Because women generally have less muscle mass and may produce less creatinine, kidney dysfunction may sometimes appear less severe than it actually is, which can contribute to delayed recognition or referral.”

In addition, women receive less CKD surveillance, and evidence-based recommendations are more slowly adopted for women, according to the statement.

“The statement was needed because women experience unique biological and life-stage factors, including pregnancy and menopause, that can affect kidney health in ways that are not fully reflected in current care models or research. The writing group aimed to bring attention to these gaps and identify opportunities to improve kidney care for women throughout their lives,” Gohar told Healio. “Kidney health is not one-size-fits-all. A woman’s menstrual health, pregnancy experiences, menopausal status and other sex-specific factors can provide important clues about current and future kidney health. The statement points out that CKD is closely connected to heart health, overall CV-kidney-metabolic health as well as reproductive health. Earlier recognition, equitable access to care and research that better reflects women’s experiences could help improve outcomes for millions of women worldwide.”

The writing committee stated that during pregnancy, renal changes include a 40% to 65% increase in eGFR attributed to increased renal blood flow, thereby reducing serum creatinine, urea and uric acid. However, for women with baseline CKD, creatinine levels of more than 1.4 mg/dL increase risk for progression of CKD and adverse pregnancy outcomes, according to the statement.

“Beyond diagnosis, women experience risk factors that men do not, including pregnancy-related complications such as preeclampsia, early menopause and conditions such as polycystic ovary syndrome,” Gohar told Healio.

“During the reproductive years, certain conditions and autoimmune diseases may increase kidney disease risk. Pregnancy creates physiological changes that can reveal underlying kidney disease. Complications such as preeclampsia are recognized as important warning signs for future problems,” Gohar said. “For women living with CKD, pregnancy requires careful planning and management because kidney function and BP can affect both maternal and fetal outcomes.”

Safe and effective contraceptives are available for women with CKD, despite longstanding concerns, and should be offered regardless of CKD stage to avoid unplanned pregnancies, according to the study.

The authors noted that contraception efficacy in people with CKD is similar to that in the general population.

Among women who are postmenopausal, declining renal function is hypothesized to be caused by estradiol loss; however, there is a paucity of studies evaluating whether menopausal hormone therapy could prevent the progression of CKD, according to the statement.

The authors added that confounding risk factors such as greater prevalence of obesity, diabetes and hyperlipidemia among postmenopausal women compared with premenopausal women may contribute to later risk for kidney disease.

“Managing well-established risk factors such as high BP, diabetes and obesity remains critically important. But women should also discuss pregnancy history, menopause status and other reproductive health factors with their healthcare team because these may offer valuable insights into kidney health,” Gohar told Healio. “At a broad level, increasing participation of women in clinical trials and incorporating reproductive health assessments into routine kidney care are all important steps toward better health outcomes for women.”

Several opportunities to improve women’s kidney care at the clinical research levels were identified in the scientific statement, with a call to action for clinical trials designed to:

• enroll more women to allow sex-specific analyses;
• identify sex-specific biomarkers for early CKD detection;
• study the impact of menstrual health, contraception, reproductive lifespan, pregnancy and menopause on risk for CKD progression;
• study the impact of social determinants of health on CKD risk in women; and
• study the impact of sex-specific effects of CKD therapeutics to optimize tailored therapy and risk management.

“We have made tremendous advances in understanding kidney disease; however, women continue to face unique challenges that are not always recognized in research or clinical care,” Gohar told Healio. “By recognizing these differences and designing research studies and health systems that better reflect women’s experiences, we have an opportunity to improve both kidney and CV health for future generations of women.”

Eman Y. Gohar, PhD, MS, FAHA, can be reached at cardiology@healio.com.