Sex Differences in Kidney Disease Identification & Treatment

Attentive observers visiting any dialysis unit in the world today, where people with kidney disease receive life-prolonging renal replacement therapy, will notice more men than women dialyzing, at an average proportion of 40% to 60%. Most doctors would reason, that this phenomenon is a consequence of high blood pressure and heart disease, causing the kidneys to fail, and affecting more men than women. However, there are several other reasons for kidney disease (diabetes, nephritis, others), touching men and women alike, or affecting women even more than affecting men. Large population-based studies actually show that more women than men classify as having kidney disease in early chronic kidney disease stages, before the disease requires renal replacement therapy. If women have at least as much early kidney disease as the men, why do fewer women than men start dialyzing? Not even the possibility of faster kidney disease progression in men seems to provide a valid explanation, if one interprets the available studies as a whole. The members of the present study team hypothesize that the under-representation of women on dialysis does not relate to biology, but instead to society, psychology, or financial issues. Important evidence in favor of this hypothesis arises from the large country-differences in the proportion of women versus men on dialysis. For example, only 32% of >75 year-old dialysis patients in Australia and New Zealand in the year 2009 were women (68% men), while 49% were women in the same age group in Canada. What makes Canada different from Australia? We hypothesize that it is the society more than the biology, and in our field of research entitled epidemiology, large regional differences in the data often suggest that. To prove or disprove our assumption, we have designed several epidemiological and biostatistical research objectives. The methodological center piece is to follow the fate of over one million people from the general population (a cohort), among them many with kidney disease. People with kidney disease either end up on dialysis, or they remain sick, and many of them will die. If the women die at faster rates than the men, but do not go on to dialysis, we will have much better proof for the assumption here above. Very refined statistical methods, however, need to be applied to render it plausible that fewer women would have died, had they been able to go on dialysis. If we receive a clear-cut statistical answer, which we believe is very well possible, according to present evidence, we will be able to start a practice-changing campaign that encourages women in Austria and elsewhere to seek timely care for their kidney disease, in the same way as the men.

Worldwide, more men than women initiate kidney replacement therapy, which explains the higher prevalence of men on dialysis (about 60 men to 40 women). In our FWF-funded project, we were able to show that this phenomenon has remained very stable over the past few decades (Antlanger M; Clin J Am Soc Nephrol 2019; 14: 1616; Kainz A; Nephrol Dial Transplant 2019; 34: 1026). However, men have a lower lifetime risk than women to become affected by chronic kidney disease (CKD), as shown by our summary of data from population- based studies in 21 countries (Carrero J J; Nat Rev Nephrol 2018; 14: 151). As part of the present project, we interviewed Nephrology experts, who stated that discrimination against women could at least partially explain the higher rate of men on dialysis (Tong A; Kidney International Reports 2021). However, biological explanations have also been held responsible, e.g. that (1) CKD progresses more slowly in women than men, (2) women with CKD suffer less frequently from cardiovascular diseases, (3) blood pressure in women is a weaker risk factor for CKD-progression than it is in men and (4) women with CKD adopt healthier lifestyles than men, which in turn may be associated with a lower risk of CKD- progression. Our FWF-funded analyses have now shown that these biological factors do not fully explain the higher probability of starting dialysis in men. In the CKD Outcomes and Practice Patterns study (Hecking M; Kidney Int Rep 2022; 7: 410) as well as the general population cohort of the Stockholm CREAtinine Measurements Project (Hodlmoser S; Kidney Int Rep 2022; 7: 444), the probability of initiating kidney replacement therapy was clearly shifted towards men, despite adjustment for age, ethnicity, comorbidities and, in particular, kidney function itself. Despite adjustment, men also had a higher probability than women, to die before kidney replacement therapy initiation. The fact that men and women compete in society has even been the subject of art (see e.g. Edgar Degas` painting "Spartan Girls Challenging Boys"). However, if survival was the ultimate goal of a human being, then men would have to be considered as losing the challenge against women, as women are well known to outlive men in the general population. In our yet unpublished investigation of concepts arising from a qualitative interview study among patients with CKD and their caretakers in Austria, we found that women with CKD might be more eager than men to self-manage their own disease. A quantitative confirmation of these results is in progress. Nevertheless, this qualitative study could already provide a different perspective: Rather than asking if women have to initiate dialysis earlier, should men possibly start dialysis later?