CKD in Patients with Bilateral Oophorectomy

Abstract

Background and objectives: Premenopausal women who undergo bilateral oophorectomy are at a higher risk of morbidity and mortality. Given the potential benefits of estrogen on kidney function, we hypothesized that women who undergo bilateral oophorectomy are at higher risk of CKD.

Design, setting, participants, & measurements: We performed a population-based cohort study of 1653 women residing in Olmsted County, Minnesota who underwent bilateral oophorectomy before age 50 years old and before the onset of menopause from 1988 to 2007. These women were matched by age (±1 year) to 1653 referent women who did not undergo oophorectomy. Women were followed over a median of 14 years to assess the incidence of CKD. CKD was primarily defined using eGFR (eGFR<60 ml/min per 1.73 m² on two occasions >90 days apart). Hazard ratios were derived using Cox proportional hazards models, and absolute risk increases were derived using Kaplan-Meier curves at 20 years. All analyses were adjusted for 17 chronic conditions present at index date, race, education, body mass index, smoking, age, and calendar year.

Results: Women who underwent bilateral oophorectomy had a higher risk of eGFR-based CKD (211 events for oophorectomy and 131 for referent women; adjusted hazard ratio, 1.42; 95% confidence interval, 1.14 to 1.77; absolute risk increase, 6.6%). The risk was higher in women who underwent oophorectomy at age ≤45 years old (110 events for oophorectomy and 60 for referent women; adjusted hazard ratio, 1.59; 95% confidence interval, 1.15 to 2.19; absolute risk increase, 7.5%).

Conclusions: Premenopausal women who undergo bilateral oophorectomy, particularly those ≤45 years old, are at higher risk of developing CKD, even after adjusting for multiple chronic conditions and other possible confounders present at index date.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_10_11_CJASNPodcast_18_1.

Keywords: Body Mass Index; Cohort Studies; Estrogens; Incidence; Menopause; Multiple Chronic Conditions; Oophorectomy; Ovariectomy; Premenopause; Proportional Hazards Models; Renal Insufficiency, Chronic; Smoking; accelerated aging; chronic kidney disease; cohort study; estrogen; glomerular filtration rate; modifiable risk factor.

Figure 1.

Incident CKD defined using eGFR values was more common in women who underwent bilateral oophorectomy. Plasma or serum creatinine (Cr) tests were extracted from the Rochester Epidemiology Project electronic indexes (available back to 1994 from the Mayo Clinic and back to 1998 from the Olmsted Medical Center). eGFR was calculated from Cr values using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as eGFR values <60 ml/min per 1.73 m² on two occasions >90 days apart. CKD present at the index date was considered prevalent, and CKD that developed on or after the index date was considered incident.

Figure 2.

Higher cumulative incidence of CKD by eGFR-based criteria (upper panels) and adjudicated diagnostic codes (lower panels) in women who underwent bilateral oophorectomy. Cumulative incidence curves estimated using the Kaplan–Meier method and adjusted using inverse probability weights are shown in red for the bilateral oophorectomy cohort and black for the referent cohort. The hazard ratios (HRs) and corresponding 95% confidence intervals were calculated using Cox proportional hazards models with age as the timescale and adjusted using inverse probability weights. Analyses are shown overall (left panels), for women age ≤45 years old at the index date (center panels), and for women age 46–49 years old at the index date (right panels).

Figure 3.

Incident CKD defined using adjudicated diagnostic codes was more common in women who underwent bilateral oophorectomy. The electronic indexes of the Rochester Epidemiology Project were screened for a list of International Classification of Diseases (ICD) diagnosis codes for CKD (ICD-8 or ICD-9). The medical records for all women with at least two of these codes separated by >30 days were then reviewed by a nephrologist. CKD was defined as an eGFR<45 ml/min per 1.73 m² or evidence of kidney damage (proteinuria or active urinary sediment) on at least two occasions >90 days apart. CKD present at the index date was considered prevalent, and CKD that developed on or after the index date was considered incident. ^aWe excluded CKD stage 3a, because it often went undiagnosed by the care providers. ^bStructural abnormalities without evidence of kidney dysfunction were not included (e.g., atrophic kidney, medullary sponge kidney, hydronephrosis, and partial or complete nephrectomy).