Consider gender differences in prevention, diagnosis and therapy

25.07.2024 15:29

Women with chronic kidney disease (CKD) receive poorer medical care than men: less early detection, fewer medications, and less dialysis. This is shown by recent clinical studies [1, 2]. These differences are not solely due to the different biological sex. Rather, gender aspects such as differences in the perception and treatment of disease are central, says the German Society for Nephrology (DGfN).

CKD increases the risk of serious comorbidities such as heart attack or stroke, as well as irreversible kidney failure. Early detection and adequate treatment are therefore crucial for a good prognosis [3]. The German Society for Neurodegenerative Diseases (DGfN) therefore calls for gender-specific consideration in CKD treatment, clinical trials, and guidelines.

In Europe and the USA, approximately 10 to 15 percent of the adult population suffers from chronic kidney disease (CKD) [1]. CKD is a serious condition characterized by a progressive decline in kidney function. In the end stage (G5), the kidneys have irreversibly lost their function, and those affected are then dependent on regular blood purification via dialysis or a kidney transplant. CKD can be triggered by infections, regular use of certain pain medications (so-called NSAIDs), autoimmune diseases, a genetic predisposition, and, above all, diabetes mellitus and high blood pressure. "Early detection and treatment include regular tests for the protein albumin in the urine, determination of the glomerular filtration rate (eGFR), and appropriate drug therapy tailored to the stage of the disease," says Professor Dr. Julia Weinmann-Menke, spokesperson for the DGfN.

"We currently see more women than men with reduced kidney function," explains Weinmann-Menke, head of the Department of Nephrology, Rheumatology and Kidney Transplantation (NTX) and the SLE Outpatient Clinic at Mainz University Hospital. Nevertheless, women with CKD receive poorer care than men, as a Swedish study has shown [4]. From diagnostics and specialist care to drug therapy, the study revealed significant deficits in the treatment of women with CKD compared to men. "Of particular concern is that the care of women over an 18-month follow-up period was worse than that of men in terms of almost all care measures," says the kidney expert. For example, they were less likely to have important markers of kidney health measured, even when risk factors such as diabetes or hypertension were present. These differences also occurred in women with confirmed CKD at the repeat examination. In addition, women in the study were less likely to receive treatment with appropriate medications such as RAS inhibitors and statins.

A large Canadian study of over 46,000 CKD patients also reported this problem. The study, conducted by the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), showed that men with chronic kidney disease receive guideline-conforming treatment more often than women [5]. "By the time those affected finally receive the correct diagnosis and then guideline-conforming treatment, their kidneys may have already partially lost their function," Weinmann-Menke points out. It has long been known that the risk of delayed initiation of dialysis, and the associated risk of mortality before the start of dialysis, is higher for women than for men [6].

Gender sensitivity: vital for survival in CKD

These differences cannot be explained solely by different biological sexes, says Weinmann-Menke. "Gender aspects are crucial, especially social factors that influence the behavior of patients and the treating physicians." Weinmann-Menke cites an example: physical complaints in women are more often interpreted as psychological signals than in men and are treated differently accordingly. The gender of the treating physicians themselves also plays a role.

There is too little knowledge and awareness regarding gender-sensitive medicine, she criticizes. In clinical trials, for example, the results are still too rarely analyzed according to gender-specific aspects. Furthermore, women were often excluded from the test subjects in the past. However, many of the drugs tested back then are still in clinical use today. "If biological sex is not taken into account when considering diseases, the influence is underestimated in 'typically male' diseases and overestimated in diseases that occur more frequently in women," states the Mainz expert. At the same time, the international KIDIGO guideline [3] also recommends that sex- and gender-specific influences should be taken into account in diagnostics, therapy, and prognosis. This includes sex-dependent differences in genetics, physiology, immunology, and anatomy, as well as gender differences (identity, role relationships, relationships).

Rethinking for better care for all kidney patients

The application of so-called gender scores could help identify the influence of cultural, societal, and psychological factors on the care of not only CKD patients, Weinmann-Menke continued. "The assessment of biological sex should therefore be part of clinical routine and prospective studies," emphasized Dr. Nicole Helmbold, Secretary General of the DGfN. "The number of people with CKD will increase significantly worldwide and in Germany in the coming years [7, 8]." This makes it all the more important to exploit all potential for prevention, early detection, and treatment and to improve the state of knowledge in Germany through our own data and research projects. "Therefore, we are committed to establishing a German Center for Kidney Health. This means a research network that will further advance research – including on this topic," said Helmbold.

Sources

1. Stracke, S., Töpfer, P., Ittermann, T. et al. Gender differences in outpatient care for people with chronic kidney disease. Nephrologie 19, 34–40 (2024). https://doi.org/10.1007/s11560-023-00698-8
2. Lösment, A., Kuhlmann, MK. Gender-specific aspects in dialysis patients. Nephrologie 19, 28–33 (2024). https://doi.org/10.1007/s11560-023-00697-9
3. KDIGO 2024, Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease, Volume 1045,|Ussue 4S, April 2024.https://kdigo.org/wp-content/uploads/2024/03/KDIGO-2024-CKD-Guideline.pdf
4. Swartling O, Yang Y, Clase CM et al. (2022) Sex differences in the recognition, monitoring, and management of CKD in health care: an observational cohort study. Journal of the American Society of Nephrology 33:1903-1914
5. Bello AK, Ronksley PE, Tangri N et al. (2019) Quality of chronic kidney disease management in Canadian primary care. JAMA network open 2:e1910704-e1910704
6. Hecking M, Bieber BA, Ethier J, Kautzky-Willer A, Sunder-Plassmann G, Säemann MD, Ramirez SP, Gillespie BW, Pisoni RL, Robinson BM, Port FK. Sex-specific differences in hemodialysis prevalence and practices and the male-to-female mortality rate: the Dialysis Outcomes and Practice Patterns Study (DOPPS). PLoS Med. 2014 Oct 28;11(10):e1001750. doi: 10.1371/journal.pmed.1001750. PMID: 25350533; PMCID: PMC4211675
7. Kovesdy CP: Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011) 2022; 12:7–11 https://doi.org/10.1016/j.kisu.2021.11.003
8. Foreman KJ, Marquez N, Dolgert A, et al.: Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016–40 for 195 countries and territories. Lancet 2018; 392: 2052-90 DOI: https://doi.org/10.1016/S0140-6736(18)316