Older men and women with chronic kidney disease (CKD) may have significant differences in terms of health-related quality-of-life (HRQOL), according to a recent study.

At the start of the study, which enrolled 1421 patients aged 65 years or older with advanced CKD but not on dialysis, women had lower average physical and mental HRQOL scores compared with men. These scores, however, declined approximately twice as fast in men as in women during a 4-year study period, Nicholas C. Chesnaye, PhD, and colleagues reported in the Clinical Journal of the American Society of Nephrology.

Better understanding of sex-specific HRQOL over the course of pre-dialysis CKD and the potential mechanisms underlying any differences may provide insights into a patient’s health and other needs, according to the investigators. “It could also aid sex-specific clinical monitoring, and the [kidney replacement therapy] decision making process,” said Dr Chesnaye, who is in the department of medical informatics at the University of Amsterdam and the Amsterdam Public Health Research Institute in The Netherlands.

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Multinational Study Population

The investigators analyzed questionnaire responses from the European Quality Study on Treatment in Advanced Chronic Kidney Diseases (EQUAL). The study included patients receiving routine medical care in Germany, Italy, the Netherlands, Poland, Sweden, and the United Kingdom.

The researchers analyzed answers to the 36-Item Short Form Survey at 3 to 6 month intervals between April 2012 and September 2020. Dr Chesnaye’s team evaluated 5,345 HRQOL measurements from 485 women and 936 men.

At baseline, patients had a mean age of 76 years and eGFR of 17 mL/min per 1.73 m2. Compared with men, women were older, more likely to be widowed, and had lower levels of education. They had higher body mass index and higher values of serum calcium, cholesterol, and potassium as well lower levels of hemoglobin, lower albumin-creatinine ratio and higher baseline eGFR. Women had a mean physical component score of 42 and mental component score of 60. Men had mean scores of 55 and 69, respectively. During the study period, physical and mental component scores declined significantly faster in men (by 2.5 and 2.7 points per year, respectively) compared with women (by 1.1 and 1.6 points per year, respectively).

The finding that women perceive an overall poorer HRQOL compared with men is consistent with what has been found in patients on dialysis and in several studies in  patients with non-dialysis dependent CKD. “The few longitudinal studies exploring the role of sex on HRQOL trajectories over time in advanced stage CKD found, in contrast to our own results, no difference in the rate of HRQOL decline between men and women,” Dr Chesnaye said.

Sex-Specific Determinants

The current study showed that decreasing kidney function occurred at a faster rate in men than women, according to the study. Higher phosphate and lower hemoglobin levels and the presence of preexisting diabetes were associated with lower physical and mental scores in men, but to a lesser extent in women. Higher serum phosphate, lower hemoglobin, and the presence of preexisting diabetes were associated with lower physical scores.

Dr Chesnaye noted that CKD is highly prevalent in adults over age 65, and with life expectancies rising, efforts to improve HRQOL in this patient population are badly needed. “Participants in our international cohort were prospectively included when their eGFR dropped below the pre-defined level of 20 mL/min/1.73 m2, thus minimizing the risk of survivor bias,” he said. “Our study is also subject to several limitations. We were unable to capture the complex interplay between demographic, psychosocial, and biological factors not collected by our study.”

Nephrologist Jennifer S. Scherer, MD, assistant professor of medicine at NYU Langone Health in New York, New York, said she was surprised by the stark differences in HRQOL between women and men. “With chronic diseases, we have to look at how the patients feel every day,” Dr Scherer said. “The study’s outcome is a patient reported outcome so we are getting important data about how people feel as a result of their disease.”

While the study has limitations, Dr Scherer said most studies focus on disease-centered outcomes. “We have to refocus our research on how the patient is experiencing their disease and how to improve any suffering,” she said.

May Be ‘Missing the Mark’

“The patient lives with the disease. If we aren’t helping them live better with their disease, then we are missing the mark. We need to see more studies that are done like this and take a longitudinal perspective. Data like these really help us when we want to set up our care models.”

Stephen Seliger, MD MS, an associate professor in the division of nephrology at the University of Maryland School of Medicine in Baltimore, said the design of the new study makes it impossible to measure many confounding variables. “The authors point out that there were important differences in medical comorbidities between men and women, and I think it explains a lot,” Dr Seliger said. “Women were more likely to be taking antidepressants. They were also heavier and had higher potassium and cholesterol levels. So, if the 2 groups had been more similar, the outcome might have been different.” 

Critical Insights

Yelena Drexler, MD assistant professor of clinical medicine in the Katz Family Division of Nephrology and Hypertension at the University of Miami in Florida, said patients who have a high burden of co-morbidities and CKD-related complications may have significantly better outcomes with a deeper understanding of sex differences regarding patient-reported outcomes. “This study provides critical insights into the intersection between sex differences and the changes in patients’ perception of their quality of life over time,” Dr Drexler said. “Future research should explore the impact of interventions targeting the potentially modifiable factors identified in this study, and whether such interventions might attenuate the sex disparities in outcomes among patients with CKD.”


Chesnaye NC, Meuleman Y, de Rooij ENM, et al. Health-related quality-of-life trajectories over time in older men and women with advanced chronic kidney disease. Clin J Am Soc Nephrol. Published online January 24, 2022. doi:10.2215/CJN.08730621