Sex-Related Disparities in CKD Progression

Abstract

Background In the United States, incidence of ESRD is 1.5 times higher in men than in women, despite men's lower prevalence of CKD. Prior studies, limited by inclusion of small percentages of minorities and other factors, suggested that men have more rapid CKD progression, but this finding has been inconsistent.Methods In our prospective investigation of sex differences in CKD progression, we used data from 3939 adults (1778 women and 2161 men) enrolled in the Chronic Renal Insufficiency Cohort Study, a large, diverse CKD cohort. We evaluated associations between sex (women versus men) and outcomes, specifically incident ESRD (defined as undergoing dialysis or a kidney transplant), 50% eGFR decline from baseline, incident CKD stage 5 (eGFR,15 ml/min per 1.73 m 2 ), eGFR slope, and all-cause death.Results Participants' mean age was 58 years at study entry; 42% were non-Hispanic black, and 13% were Hispanic. During median follow-up of 6.9 years, 844 individuals developed ESRD, and 853 died. In multivariable regression models, compared with men, women had significantly lower risk of ESRD, 50% eGFR decline, progression to CKD stage 5, and death. The mean unadjusted eGFR slope was 21.09 ml/min per 1.73 m 2 per year in women and 21.43 ml/min per 1.73 m 2 per year in men, but this difference was not significant after multivariable adjustment.Conclusions In this CKD cohort, women had lower risk of CKD progression and death compared with men. Additional investigation is needed to identify biologic and psychosocial factors underlying these sexrelated differences.Although women in the United States have a greater prevalence of CKD compared with men, men are 1.5 times more likely to develop ESRD. The reasons for this sex-related disparity are not well understood. In their prospective cohort study evaluating sex-related differences in CKD progression, the authors evaluated data from 3939 adults enrolled in the Chronic Renal Insufficiency Cohort Study, a large and diverse CKD cohort. They find a lower risk of ESRD and death from any cause in women compared with men, and these differences remained statistically significant, even after adjustment for sociodemographic characteristics, baseline kidney function, cardiovascular risk factors, medications, and markers of bone mineral metabolism. Additional research is needed to elucidate biologic and psychosocial factors underlying the sex-related difference in CKD progression.

Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies

“…32 Results of the present study agree with a very recent report from the CRIC Investigators demonstrating lower risk for ESKD in women that is similar to what is estimated in our study. 10 The results in the CRIC Study were obtained in a low-risk cohort of patients with CKD, as evidenced by the incidence rate of ESKD (3.1/100 personyears in women and 3.8/100 person-years in men) much lower than that observed in our patients (7.2 and 8.5/100 person-years in women and men, respectively), likely related to a higher eGFR, lower proteinuria, and lower BP in the CRIC cohort. 10 Therefore, our data extend the observation of the CRIC study to elderly patients with more severe CKD.…”

“…10 The results in the CRIC Study were obtained in a low-risk cohort of patients with CKD, as evidenced by the incidence rate of ESKD (3.1/100 personyears in women and 3.8/100 person-years in men) much lower than that observed in our patients (7.2 and 8.5/100 person-years in women and men, respectively), likely related to a higher eGFR, lower proteinuria, and lower BP in the CRIC cohort. 10 Therefore, our data extend the observation of the CRIC study to elderly patients with more severe CKD. A large meta-analysis of 68 studies including 11,345 patients reported a higher occurrence of kidney replacement therapy or faster decline in eGFR in men than women.…”

“…In all previous studies, progression of kidney disease-assessed as either ESKD, doubling of serum creatinine level, or eGFR decline over time-has been investigated in CKD populations as a whole. [6][7][8][9][10] We found that the higher risk for ESKD in men persisted in all CKD stages examined (from 3b to 5; Table 2). The lack of heterogeneity across stages reinforces the message that renal prognosis is worse in men than in women independent of the initial level of kidney function.…”

“…9 Very recently, faster CKD progression has been reported in men enrolled in the CRIC Study in terms of risk for ESKD, 50% decline in estimated glomerular filtration rate (eGFR), and incident CKD stage 5. 10 The discrepancy with the available findings could be ascribed to the inclusion of studies with a difference in the design (observational vs randomized trials), differences in age of sex subgroups (and therefore different proportion of premenopausal women), lack of contemporary assessment of mortality rates that may strongly influence the estimate of renal risk (competing risk), and differences in the study setting (general population and tertiary nephrology care). 11,12 To evaluate the potential effect of sex on CKD progression, we compared men and women with moderate to advanced CKD in a multicohort study group regularly followed up in renal clinics in Italy.…”

Sex Differences in Diabetic Kidney Disease

“…A large meta-analysis published in 2000, and also a more recent analysis of the Chronic Renal Insufficiency Cohort (CRIC) reported that male sex is associated with a more rapid rate of progression and a worse renal outcome in patients with nondiabetic chronic kidney disease (CKD). 16,17 These observations suggest that the female sex is protective factor for nondiabetic CKD; however, this may only hold true in younger, premenopausal women. Indeed, after adjustment for confounding factors, a study which included mainly postmenopausal women reported that women appear to have as high, or even a higher, rate of nondiabetic CKD progression as men.…”