Dataset Information

Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy.

ABSTRACT:

Background

Pregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR).

Objective

To compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA).

Study design

Four groups of 20 normotensive, nulliparous women were studied in Lagos, Nigeria: pregnant HbSS or HbAA women at 36-40 weeks gestation; non-pregnant HbSS and HbAA controls. We measured stable metabolites of prostacyclin and thromboxane A2 by enzyme-linked immunosorbent assay; GFR using the Cockcroft-Gault equation. Data analysis was by independent (Student's) t-test or Mann-Whitney U test for comparisons between any two groups of continuous variables, univariate ANOVA for multiple groups and Pearson's correlation coefficient for degree of association between variables.

Results

HbSS women had lower serum 6-keto-PGF1? concentrations than HbAA, whether pregnant or non-pregnant (P<0.001; P<0.004 respectively). Conversely, pregnant HbSS women had higher serum TxB2 (P<0.001); non-pregnant HbSS women had non-significantly higher TxB2 concentrations. The 6-keto-PGF1?:TxB2 ratio was markedly increased (pro-vasodilatory) in HbAA pregnancy (P<0.001) but reduced in HbSS pregnancy (P = 0.037). GFRs (mL/min) were higher in non-pregnant HbSS than HbAA (P<0.008) but only marginally raised in HbSS women in late pregnancy (P = 0.019) while markedly raised in HbAA pregnancy (P<0.001).

Conclusion

The lower ratio of prostacyclin-thromboxane metabolites in HbSS pregnancy may indicate endothelial damage and an increased tendency to vasoconstriction and clotting. If confirmed by subsequent longitudinal studies, interventions to increase prostacyclin and reduce thromboxane, such as low dose aspirin, may be potentially useful in their management.

SUBMITTER: Obilade OA

PROVIDER: S-EPMC5589233 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy.

Obilade Opeyemi Abayomi OA Akanmu Alani Suleimon AS Broughton Pipkin Fiona F Afolabi Bosede Bukola BB

PloS one 20170907 9

<h4>Background</h4>Pregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filt ...[more]

PMID: 28880908

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Project description:BackgroundEquations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values.ObjectiveTo develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.DesignCross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates.SettingResearch studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006.Participants8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES.MeasurementsGFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age.ResultsIn the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%).LimitationThe sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR.ConclusionThe CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.Primary funding sourceNational Institute of Diabetes and Digestive and Kidney Diseases.

Project description:IntroductionGlomerular filtration rate (GFR) is typically estimated with equations that use biomarkers such as serum creatinine and/or cystatin-C. The impact of these different biomarkers on GFR estimates in glomerular disease patients is unclear. In this study, we compared the different GFR estimating equations in the Cure Glomerulonephropathy (CureGN) cohort of children and adults with glomerular disease.MethodsAll available cystatin-C measurements from CureGN study participants were matched to same-day serum creatinine measurements to estimate GFR. To explore the strength of agreement between eGFR values obtained from the "Under 25" (U25) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations, we used intraclass correlation coefficients. Multivariable linear mixed effects models were used to determine which factors were independently associated with differences in eGFR values.ResultsA total of 928 cystatin-C measurements were matched to same-day serum creatinine measurements from N = 332 CureGN study participants (58% male, 69% White/Caucasian, 20% Black/African American). Among 628 measurements collected while study participants were under 25 years old, there was moderate agreement (0.731) in serum creatinine versus cystatin-C U25 equations. Models showed that higher eGFR values were associated with larger differences between the two equations (p < 0.001). Among 253 measurements collected while study participants were at least 18 years old, there was excellent agreement (0.891-0.978) among CKD-Epi equations using serum creatinine alone, cystatin-C alone, or the combination of both. Younger age was associated with larger differences between CKD-Epi equations (p = 0.06 to p = 0.016).ConclusionExcellent agreement between CKD-Epi equations indicates continued use of serum creatinine alone for GFR estimation could be appropriate for adults. In contrast, only moderate agreement between U25 equations indicates a need for more frequent measurement of cystatin-C among children and young adults, especially as eGFR increases.

Dataset Information

Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy.

Background

Objective

Study design

Results

Conclusion

Publications

Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy.

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