Dataset Information

Preeclampsia and ESRD: The Role of Shared Risk Factors.

ABSTRACT:

Background

Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors.

Study design

Population-based nested case-control study.

Setting & participants

The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or ≥4).

Predictor

Preeclamptic pregnancy, confirmed by medical record review.

Outcome

ESRD.

Measurements

Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension.

Results

There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (<1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88 (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21-13.28). Results were similar after independent adjustment for race, education, diabetes, and hypertension prior to pregnancy. However, the association was attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95% CI, 0.93-11.37).

Limitations

The limited number of ESRD cases and missing data for prepregnancy kidney function.

Conclusions

Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed.

SUBMITTER: Kattah AG

PROVIDER: S-EPMC5366077 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preeclampsia and ESRD: The Role of Shared Risk Factors.

Kattah Andrea G AG Scantlebury Dawn C DC Agarwal Sanket S Mielke Michelle M MM Rocca Walter A WA Weaver Amy L AL Vaughan Lisa E LE Miller Virginia M VM Weissgerber Tracey L TL White Wendy W Garovic Vesna D VD

American journal of kidney diseases : the official journal of the National Kidney Foundation 20161001 4

<h4>Background</h4>Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors.<h4>Study design</h4>Population-based nested case-control s ...[more]

PMID: 27707553

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Project description:Background and objectivesHemostatic factors have been associated with kidney function decline, and evidence suggests stronger effects among African Americans. The presence of APOL1 renal risk variants, common in African Americans, might partly underlie this risk difference.Design, setting, participants, & measurementsA total of 13,337 participants in the Atherosclerosis Risk in Communities study were followed from 1987-1989 until 2010. Participants were categorized into three groups by ancestry and APOL1 risk status: European Americans (n=10,206), African Americans with zero or one APOL1 risk allele (n=2,733), and African Americans with two APOL1 risk alleles (n=398). ESRD events were ascertained through linkage to the US Renal Data System. Cox regression was used to estimate the risk for ESRD associated with hemostatic factors (factor VIIc, factor VIIIc, fibrinogen, von Willebrand factor, protein C, and antithrombin III).ResultsThere were 232 cases of ESRD over 21.5 years (European Americans, 119; African Americans with zero or one APOL1 risk allele, 94; African Americans with two APOL1 risk alleles, 19). In unadjusted and adjusted analysis of the overall population, higher levels of all hemostatic factors, except antithrombin III, were significantly associated with ESRD (all P<0.05). Factor VIIc had the strongest association (per one interquartile range; adjusted hazard ratio, 1.46; 95% confidence interval, 1.21 to 1.76). With the exception of fibrinogen, the risk associated with each hemostatic factor was stronger in African Americans with two APOL1 risk alleles compared with the other two groups. Statistically significant interactions were seen for factor VIIIc and protein C (interaction between those with two APOL1 risk allele and the other two groups: P<0.02 for factor VIIIc and <0.04 for protein C).ConclusionsHigher levels of factor VIIc, VIIIc, fibrinogen, von Willebrand factor, and protein C were associated with ESRD risk, with a significantly stronger association of factor VIIIc and protein C in African Americans with two APOL1 risk alleles.

Project description:ImportancePreeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Within-country studies have reported racial differences in the presentation and outcome, but little is known about differences between countries.ObjectiveTo compare preeclampsia prevalence, risk factors, and pregnancy outcomes between the Swedish and Chinese populations.Design, setting, and participantsThis cross-sectional study compared deliveries from the Swedish national Medical Birth Register (2007-2012) and the China Labor and Delivery Survey (2015-2016). The Swedish Medical Birth Register records maternal, pregnancy, and neonatal information for nearly all deliveries in Sweden. The China Labor and Delivery Survey was conducted throughout China, and these data were reweighted to enable national comparisons. Participants included 555 446 deliveries from Sweden and 79 243 deliveries from China. Data management and analysis was conducted from November 2018 to August 2020 and revised in February to March 2021.ExposuresMaternal characteristics, parity, multiple gestation, chronic and gestational diabetes, cesarean delivery.Main outcomes and measuresPreeclampsia prevalence and risk factors, overall and for mild and severe forms and rates of adverse neonatal outcomes compared with pregnancies with no gestational hypertension.ResultsThe 555 446 Swedish pregnancies and 79 243 Chinese pregnancies had mean (SD) maternal age of 30.9 (5.3) years and 28.6 (4.6) years, respectively. The overall prevalence of preeclampsia was similar in Sweden and China, 16 068 (2.9%) and 1803 (2.3%), respectively, but with 5222 cases (32.5%) considered severe in Sweden and 1228 cases (68.1%) considered severe in China. Obesity (defined as BMI ≥28 in China and BMI ≥30 in Sweden) was a stronger risk factor in China compared with Sweden (China: odds ratio [OR], 5.12; 95% CI, 3.82-6.86; Sweden: OR, 3.49; 95% CI, 3.31-3.67). Nulliparity had a much stronger association with severe preeclampsia in Sweden compared with China (Sweden: OR, 3.91; 95% CI, 3.65-4.18; China: OR, 1.65; 95% CI, 1.20-2.25). The overall stillbirth rate for singleton in China was more than 3-fold higher than in Sweden (846/77 512[1.1%] vs 1753/547 219 [0.3%], P < .001), and 10-fold higher among women with preeclampsia (66/1652 [4.6%] vs 60/14 499[0.4%], P < .001).Conclusions and relevanceIn this study, the prevalence rates of preeclampsia in Sweden and China were similar, but women in China had more severe disease and worse pregnancy outcomes than women in Sweden. The associations of obesity and nulliparity with preeclampsia suggest a role for lifestyle and health care factors but may reflect some differences in pathophysiology. These findings have relevance for current efforts to identify high-risk pregnancies and early serum markers because the value of risk prediction models and biomarkers may be population specific.

Project description:ImportanceA genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.ObjectiveTo disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.Design, setting, and participantsThis GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023.ExposuresThe association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.ResultsA total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP).Conclusions and relevanceThe findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.

Dataset Information

Preeclampsia and ESRD: The Role of Shared Risk Factors.

Background

Study design

Setting & participants

Predictor

Outcome

Measurements

Results

Limitations

Conclusions

Publications

Preeclampsia and ESRD: The Role of Shared Risk Factors.

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