The effect of gender on survival for hemodialysis patients: Why don't women live longer than men?

Women in the general population have a survival advantage over men, but this advantage is not sustained in end-stage kidney disease (ESKD) patients treated by hemodialysis. To understand why gender may affect survival we need to understand confounders which may affect dialysis practices. The current paradigm is to prescribe hemodialysis to achieve a target dialyzer urea clearance adjusted to total body water volume (Kt/Vurea ). Estimated glomerular filtration calculated from serum creatinine is often used to determine when patients start dialysis; as creatinine generation rates are lower in women, this may potentially result in a lead time bias with male patients starting dialysis earlier than females. When hemodialysis dose is scaled to total body water (Kt/Vurea ) women receive shorter dialysis session times. Scaling dialysis for body surface area may be more appropriate since urea generation (a surrogate for uremic toxin production) depends upon resting energy expenditure (ie, cellular metabolism) which reflects internal organ sizes. Resting energy expenditure is proportionally greater for smaller people. Women are generally smaller than men and as such have smaller sized internal organs. However, when comparing individuals, then internal organ size is best adjusted for using body surface area, not body water. The shorter, resultant dialysis session also results in lower middle molecule clearances, increases fluid removal rates and the risk of intra-dialytic hypotension; the latter potentially results in earlier loss of residual renal function. Observational studies report that the association between survival and dialyzer Kt/Vurea is improved after adjustment for body surface area, or energy expenditure. These studies also demonstrated that the conventional prescription of hemodialysis based on current Kt/Vurea targets leads to less treatment delivered to women. These multiple consequences of the generally smaller size of women compared with men may account for the unexpectedly higher relative mortality for women. As such, prospective studies investigating alternative scaling parameters are required to confirm that increasing dialysis treatments for women improves survival.