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Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies.
Am J Kidney Dis. 2020 01; 75(1):30-38.AJ

Abstract

RATIONALE & OBJECTIVE

Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine.

STUDY DESIGN

Pooled analysis of 4 Italian observational cohort studies.

SETTING & PARTICIPANTS

1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR)<45mL/min/1.73m2 followed up in renal clinics.

PREDICTOR

Sex.

OUTCOMES

End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes.

ANALYTICAL APPROACH

Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline.

RESULTS

Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6±10.2 in men and 26.0±10.6mL/min/1.73m2 in women (P<0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P<0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of ∼0.5g/d or greater. The slope of decline in eGFR was steeper in men (-2.09; 95% CI, -2.21 to-1.97mL/min/1.73m2 per year) than in women (-1.79; 95% CI, -1.92 to-1.66mL/min/1.73m2 per year; P<0.001). Although sex differences in eGFR decline were not different across CKD stages (P=0.3), the difference in slopes between men and women was progressively larger with proteinuria >0.5g/d (P = 0.04).

LIMITATIONS

Residual confounding; only whites were included.

CONCLUSIONS

Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women.

Authors+Show Affiliations

Division of Nephrology, University of Campania, Luigi Vanvitelli, Naples, Italy. Electronic address: roberto.minutolo@unicampania.it.Department of Medicine, VA San Diego Healthcare System and University of California at San Diego Medical School, San Diego, CA.Medical Statistics Unit, University of Campania, Luigi Vanvitelli, Naples, Italy.Division of Nephrology, University of Campania, Luigi Vanvitelli, Naples, Italy.Division of Nephrology, University of Campania, Luigi Vanvitelli, Naples, Italy.Division of Nephrology, University of Campania, Luigi Vanvitelli, Naples, Italy.Nephrology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy.Department of Public Health, University Federico II, Naples, Italy.Division of Nephrology, University of Campania, Luigi Vanvitelli, Naples, Italy.Division of Nephrology, University of Campania, Luigi Vanvitelli, Naples, Italy.No affiliation info available

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

31409508

Citation

Minutolo, Roberto, et al. "Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 75, no. 1, 2020, pp. 30-38.
Minutolo R, Gabbai FB, Chiodini P, et al. Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies. Am J Kidney Dis. 2020;75(1):30-38.
Minutolo, R., Gabbai, F. B., Chiodini, P., Provenzano, M., Borrelli, S., Garofalo, C., Bellizzi, V., Russo, D., Conte, G., & De Nicola, L. (2020). Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 75(1), 30-38. https://doi.org/10.1053/j.ajkd.2019.05.019
Minutolo R, et al. Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies. Am J Kidney Dis. 2020;75(1):30-38. PubMed PMID: 31409508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies. AU - Minutolo,Roberto, AU - Gabbai,Francis B, AU - Chiodini,Paolo, AU - Provenzano,Michele, AU - Borrelli,Silvio, AU - Garofalo,Carlo, AU - Bellizzi,Vincenzo, AU - Russo,Domenico, AU - Conte,Giuseppe, AU - De Nicola,Luca, AU - ,, Y1 - 2019/08/10/ PY - 2018/12/21/received PY - 2019/05/12/accepted PY - 2019/8/15/pubmed PY - 2020/4/21/medline PY - 2019/8/15/entrez KW - Chronic kidney disease (CKD) KW - eGFR decline KW - end-stage kidney disease (ESKD) KW - epidemiology KW - estimated glomerular filtration rate (eGFR) KW - older adults KW - outcomes KW - proteinuria KW - renal disease progression KW - sex KW - sex differences SP - 30 EP - 38 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 75 IS - 1 N2 - RATIONALE & OBJECTIVE: Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine. STUDY DESIGN: Pooled analysis of 4 Italian observational cohort studies. SETTING & PARTICIPANTS: 1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR)<45mL/min/1.73m2 followed up in renal clinics. PREDICTOR: Sex. OUTCOMES: End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes. ANALYTICAL APPROACH: Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline. RESULTS: Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6±10.2 in men and 26.0±10.6mL/min/1.73m2 in women (P<0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P<0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of ∼0.5g/d or greater. The slope of decline in eGFR was steeper in men (-2.09; 95% CI, -2.21 to-1.97mL/min/1.73m2 per year) than in women (-1.79; 95% CI, -1.92 to-1.66mL/min/1.73m2 per year; P<0.001). Although sex differences in eGFR decline were not different across CKD stages (P=0.3), the difference in slopes between men and women was progressively larger with proteinuria >0.5g/d (P = 0.04). LIMITATIONS: Residual confounding; only whites were included. CONCLUSIONS: Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/31409508/Sex_Differences_in_the_Progression_of_CKD_Among_Older_Patients:_Pooled_Analysis_of_4_Cohort_Studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(19)30841-8 DB - PRIME DP - Unbound Medicine ER -