Renal biomarkers in pre-eclampsia and their associations with severity of pre-eclampsia

Paschalina C Ezechukwu; Emmanuel O Ugwu; Samuel N Obi; George U Eleje; Polycarp U Agu; Emeka I Iloghalu; Kingsley C Obioha; Chidinma I Onwuka; Angela O Ugwu; Obinna D Onodugo; Benjamin C Ozumba

doi:10.4103/ijmh.IJMH_11_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 28 | Issue : 1 | Page : 7-11

Renal biomarkers in pre-eclampsia and their associations with severity of pre-eclampsia

Paschalina C Ezechukwu¹, Emmanuel O Ugwu², Samuel N Obi², George U Eleje³, Polycarp U Agu², Emeka I Iloghalu², Kingsley C Obioha¹, Chidinma I Onwuka², Angela O Ugwu⁴, Obinna D Onodugo⁵, Benjamin C Ozumba²
¹ Department of Obstetrics & Gynaecology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
² Department of Obstetrics & Gynaecology, College of Medicine, University of Nigeria, Ituku-Ozalla Campus, Enugu, Nigeria
³ Department of Obstetrics & Gynaecology, College of Health Sciences, Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria
⁴ Department of Haematology & Immunology, College of Medicine, University of Nigeria, Ituku-Ozalla Campus, Enugu, Nigeria
⁵ Department of Internal Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla Campus, Enugu, Nigeria

Date of Submission	08-Feb-2022
Date of Decision	15-Mar-2022
Date of Acceptance	15-Sep-2022
Date of Web Publication	13-Dec-2022

Correspondence Address:
Emeka I Iloghalu
Department of Obstetrics & Gynaecology, College of Medicine, University of Nigeria, Ituku-Ozalla Campus, Enugu
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmh.IJMH_11_22

Abstract

Background: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and mortality in Nigeria and worldwide. It is not yet concluded as to whether or not elevated levels of serum creatinine and/or uric acid could be regarded as a predictive indicator for the severity of the disease. Objectives: To compare the mean serum levels of uric acid and creatinine in preeclamptic and normotensive pregnant women and assess for any associations between these renal biomarkers and the severity of preeclampsia in Nigeria. Materials and Methods: It was a cross-sectional analytical study of 132 women with preeclampsia (n = 61) and normotensive pregnant women (n = 61). The study group comprised eligible consecutive women diagnosed with preeclampsia, whereas the control group comprised appropriately matched normotensive pregnant women. Main outcome measures included the mean serum levels of uric acid and creatinine in both groups, and their levels in cases with mild and severe degrees of preeclampsia. Results: The mean serum levels of uric acid and creatinine were significantly higher in women with preeclampsia than in normotensive pregnant women (7.67 ± 2.9 versus 4.56 ± 1.1; P < 0.001, and 0.76 ± 0.3 versus 0.53 ± 0.1; P < 0.001, respectively). There was no significant difference in the mean serum levels of uric acid and creatinine in women with mild and severe degrees of preeclampsia (6.66 ± 2.3 versus 7.77 ± 2.9; P = 0.37, and 0.56 ± 0.2 versus 0.79 ± 0.4; P = 0.12, respectively). Conclusions: This study has demonstrated that serum uric acid and serum creatinine levels are elevated in pregnancies complicated by preeclampsia. However, there is no significant association between serum levels of these renal biomarkers and the severity of preeclampsia. The studied renal biomarkers are therefore important in the diagnostic workup of preeclampsia but of limited value in the disease prognostication.

Keywords: Creatinine levels, preeclampsia, renal biomarkers, uric acid

How to cite this article:
Ezechukwu PC, Ugwu EO, Obi SN, Eleje GU, Agu PU, Iloghalu EI, Obioha KC, Onwuka CI, Ugwu AO, Onodugo OD, Ozumba BC. Renal biomarkers in pre-eclampsia and their associations with severity of pre-eclampsia. Int J Med Health Dev 2023;28:7-11

How to cite this URL:
Ezechukwu PC, Ugwu EO, Obi SN, Eleje GU, Agu PU, Iloghalu EI, Obioha KC, Onwuka CI, Ugwu AO, Onodugo OD, Ozumba BC. Renal biomarkers in pre-eclampsia and their associations with severity of pre-eclampsia. Int J Med Health Dev [serial online] 2023 [cited 2023 Jun 5];28:7-11. Available from: https://www.ijmhdev.com/text.asp?2023/28/1/7/363248

Introduction

Preeclampsia is one of the leading causes of maternal and perinatal morbidity and mortality in Nigeria and worldwide.^{[1],[2],[3],[4]} The incidence is about 5%–10% of all pregnancies though there are variations depending on the population studied.^[1],[5] The etiology is generally unknown and thus has been described as a disease of theories. The pathology is largely linked to abnormal placentation, and this may explain why definitive treatment is the delivery of the placenta.^[6]

In view of the clinical relevance of this condition, some authors have investigated the role of several biomarkers including serum uric acid and creatinine in the pathogenesis of the disease.^[5]

There are conflicting reports regarding serum concentration of uric acid and creatinine in preeclampsia. Some researchers reported significantly elevated values of plasma uric acid and creatinine,^[6],[7] whereas others reported no significant difference in the mean values of plasma levels of the two biomarkers.^[8],[9]

It is also not yet concluded as to whether or not elevated levels of serum creatinine or uric acid reported by some researchers could be regarded as a predictive indicator for the severity of the disease.^[5] Furthermore, there is a paucity of data regarding the serum levels of these biochemical parameters in women with preeclampsia in Sub-Saharan Africa where the disease burden is high. The study findings may help in guiding obstetricians in taking appropriate management decisions especially with regard to the prognosis and severity of the disease. This study therefore aimed at evaluating the serum uric acid and creatinine levels among preeclamptic and healthy normotensive women who booked for antenatal care or presented in labor at two large health institutions in Enugu, South East Nigeria. The objective was to compare the mean serum levels of uric acid and creatinine in preeclamptic and normotensive pregnant women and to assess for any associations between these renal biomarkers and the severity of preeclampsia in Nigeria.

Materials and Methods

This was a cross-sectional analytical study of 132 women with preeclamptic and normotensive pregnant women receiving antenatal care at the antenatal clinics of the University of Nigeria Teaching Hospital (UNTH), Ituku/Ozalla, Enugu and Mother of Christ Specialist Hospital (MOCSH), Enugu, Nigeria. The unbooked pregnant women presenting with preeclampsia in the two hospitals were also included. The study took place between March and October 2017. The UNTH is the largest tertiary health institution in the South-East region of Nigeria, and it is a federal government health institution. The MOCSH, on the other hand, is a private mission hospital funded by the Immaculate Heart Sisters. Both hospitals provide antenatal services, delivery, emergency obstetric and family planning services. They operate the traditional model of antenatal care in which women are usually seen four weekly until 28 weeks, fortnightly until 36 weeks, and weekly until the delivery. Both hospitals have a very high client flow for maternity. Written informed consent was obtained from each participant before recruitment into the study, and ethical approval was obtained from the Ethics Committee of UNTH, Ituku-Ozalla, Enugu (UNTH/CSA/329/OL.5: NHREC/05/01/2008B-FWA00002458-1RB00002323). All the guidelines outlined in the Declaration of Helsinki were met.

All pregnant women with a diagnosis of preeclampsia were eligible for the study. The exclusion criteria included diabetes mellitus, multiple gestation, obesity, severe anemia (Hb <6 g%), history of urinary tract infection, renal disorders, liver disorders, chronic illnesses including human immunodeficiency virus infection, malignancy, and tuberculosis. Women who smoke and those suffering from other systemic or endocrine disorders were also excluded.

Pregnant women in their third trimester (28–40 weeks) attending the antenatal clinic or presenting as unbooked cases and meeting with the outline study criteria were consecutively recruited. Thus, once a woman with preeclampsia was deemed eligible for the study and had given informed consent, she was recruited and given a study number. Then, a suitable normotensive (control) antenatal clinic attendee matched for age group, parity group, and gestational age group categories was also recruited. The anthropometric measurements and sociodemographic characteristics of the two study groups were obtained by taking a brief relevant medical history and conducting a physical examination. Their weights were measured to the nearest 0.5 kg, and their heights to the nearest in 0.1 m. A stadiometer was used for measuring both parameters. For the measurement of height, readings were taken with the patients standing erect without shoes, feet placed together, and eyes level and looking ahead. Proteinuria was defined as 0.3 g (300 mg) or more of protein in a 24-h urine collection or protein of 2+ or more on a urine dipstick test in a minimum of two random urine samples collected 4 h apart.^[1],[10] Mild preeclampsia was defined as a blood pressure of ≥140–159/90–109 mmHg with two measurements taken 4 h apart in association with proteinuria of 0.3 g or more in a 24-h urine collection but less than 5 g.^[1] Severe preeclampsia was defined as a blood pressure of ≥160/110 mmHg in association with proteinuria of 5 g or more in a 24-h urine collection or proteinuria of 3+ or more on an urinary dipstick examination. The diagnosis of severe preeclampsia was also made in the presence of any of the following possible associated features: oliguria (<400 mL of urine in 24 h) or renal failure, epigastric or the right hypochondrial pain, pulmonary edema, impaired liver function test, thrombocytopenia, oligohydramnios, intrauterine growth restriction, placental abruption, frontal headaches, maternal neurological disturbances, and haemolysis, elevated liver enzyme, low platelet count (HELLP) syndrome.^[1],[10] Blood pressure of participants was measured using the manual sphygmomanometer machine while the patient was in a sitting position.

Biochemical data measured included serum uric acid and creatinine levels and urine protein level. In each patient, 8 mL of venous blood was collected under aseptic procedure in ethylenediamine tetraacetic acid (EDTA)-treated tubes from the cubital vein of her preferred hand. The serum uric acid concentration was measured by colorimetric assay.^[11] The concentration of serum creatinine levels was measured using Jaffe reaction method.^[12] These two tests were carried out by chemical pathologists working in the medical laboratory of UNTH, Ituku/Ozalla, Enugu. The participants were instructed to abstain from taking coffee or chocolates for not less than 2 h before presenting for blood sample collection, because of possible effects of these two agents on the serum concentration of uric acid and creatinine.

The calculation of the required sample size was based on the formula for calculating the difference in mean (sample size), by Kirkwood.^[13] Using a mean standard deviation (SD) of 1.5 mg/dL for mean uric acid (SD = 1.5 and variance = (1.5)2 = 2.25) obtained from a previous related study,^[14] the minimum sample size (n) was calculated as n = 58.5. Assuming an attrition rate of 10% for possible losses and nonresponders, the minimum sample size was 55 for each group. However, a sample size of 66 for each group, making a total of 132, was used for the study.

Statistical analysis was done using the statistical package for social sciences (SPSS) computer software version 24. The collected data were compared between the two groups. Means ± SDs were obtained for continuous variables, whereas frequency and proportions were used to summarize categorical variables. Means of continuous variables were compared using Student’s t test, whereas proportions were compared using chi-square test. All tests were two-sided, and the statistical significance was considered to be at a probability value of <0.05.

Results

A total of 66 participants were recruited in each group and they all participated in the study to the end. The two groups were similar in their baseline characteristics including as age, parity, gestational age, and educational level categories. Details were as shown in [Table 1].

Table 1: Baseline demography of the study participants

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The mean serum uric acid was higher in the preeclampsia group than in the control group (7.7 ± 2.9 versus 4.6 ± 1.1; P < 0.001). Similarly, the mean serum creatinine level was higher in the preeclampsia group than in the control group (0.8 ± 0.3 versus 0.5 ± 0.1; P < 0.001). Details are as shown in [Table 2].

Table 2: Mean comparison of serum uric acid and creatinine concentration between preeclamptic and normotensive women

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Among the 66 participants with preeclampsia, six (9%) had mild preeclampsia, whereas 60 (91%) had severe preeclampsia.

There was no significant difference in mean serum uric acid levels in participants with mild preeclampsia when compared with severe preeclampsia (6.7 ± 2.3 versus 7.8 ± 2.9; P = 0.37). Similarly, there was no significant difference in mean serum creatinine levels between participants with mild preeclampsia and severe preeclampsia (0.5 ± 0.2 versus 0.8 ± 0.4; P = 0.12). Details are as shown in [Table 3].

Table 3: Comparison of mean serum uric acid and creatinine between mild and severe preeclamptic women

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Discussion

The result of the present study showed that a mean serum uric acid was significantly increased in preeclamptic women compared with normotensive pregnant women. A likely explanation for this observation may be due to the rise in the reabsorption of serum uric acid and reduction in its excretion in proximal convoluted tubules of the kidneys following the disease.^[2],[3] Induced oxidative stress and the formation of oxygen radicals could also contribute to the pathogenesis of the observed hyperuricemia in preeclampsia.^[3],[5] The elevation in the level of uric acid in preeclampsia observed in this study is similar to some previously related study.^{[3],[5],[6],[15],[16],[17],[18]} Some researchers, however, have found no significant difference in serum uric acid levels between women with preeclampsia and those without preeclampsia.^[8] The heterogeneity in the study designs may account for some of the differences observed in the studies’ estimates. For instance, the above study that reported no difference in serum uric acid level investigated only primigravidae at their early gestations.

Some previous researchers found that the extent of elevation of serum uric acid level in preeclampsia was indicative of the severity of the disorder.^{[19],[20],[21]} It has also been suggested that the elevated serum uric acid level is an important cofactor in the pathogenesis and manifestation of preeclampsia.^[5] Although serum uric acid level was observed in the present study to be higher in preeclamptic than normotensive women, the elevated level did not have any associations with the severity of the disease. This observation is similar with findings from a recent report.^[5] These conflicting results suggest that there is still a need for further studies in this direction.

Similar to uric acid level, studies on plasma concentration of creatinine in preeclampsia versus normotensive women have revealed controversial results with some authors reporting elevated levels, whereas others found no significant difference. The significantly raised creatinine in women with preeclampsia observed in this study was similar as reported by some previous authors.^{[5],[7],[18],[22]} Nevertheless, some other researchers^[8],[9] have observed the absence of any associations between serum creatinine in women with preeclampsia and the normotensive women.

The limitations of this study include the fact that although the women were instructed to abstain from coffee and chocolates for not less than 2 h before presenting for blood sample collection, there were no measurements of these oxidative stress-inducing agents, which may affect the serum concentration of uric acid and creatinine.

In conclusion, serum uric acid and creatinine are increased in pregnancies complicated by preeclampsia compared with normal pregnancies. However, the degree of rise in these biomarkers did not have any relationships with the severity of the disease and thus may not be of high predictive value. Further studies with a larger sample size are necessary to corroborate these observations. A follow-up study on the effect of these elevated biomarkers on pregnancy outcome is also highly desirable.

Acknowledgement

The authors wish to acknowledge that the abstract of this article was made available and presented as “Oral/Free Communication Session Abstracts,” International Journal of Gynecology and Obstetrics, at FIGO’s XXII World Congress, held in Rio De Janeiro, Brazil, in 2018.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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