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Sympathetic Overactivity Predicts Microalbuminuria in Pregnancy

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Sympathetic Overactivity Predicts Microalbuminuria in Pregnancy Original Article DOI: 10.7860/JCDR/2018/36738.12412 Sympathetic Overactivity Predicts Section Biochemistry Microalbuminuria in Pregnancy INDER PAL KAUR1, SUKANYA GANGOPADHYAY2, KIRAN SINGH3, MAMTA TYAGI4, GAUTAM SARKAR5 ABSTRACT pregnancy-induced hypertension. Statistical analysis was done Introduction: Microalbuminuria is a frequent feature in with appropriate tests using Graphpad Prizm (version 7.04). pregnancy, as the latter is a state of haemodynamic changes Results: The level of urinary microalbumin was found to be and sympathetic overactivity. Both sympathetic overactivity {as high in the pregnant group. Albumin Creatinine Ratio (ACR) was measured by Heart Rate Variability (HRV)} and microalbuminuria raised in pregnancy (72.35±50.29 in third trimester, 84.48±52.61 are individually linked with hypertension. So, presence of these in second trimester and 17.59±6.19 in non-pregnant control conditions in pregnant women could be the reason for the group; p<0.001). The HRV study shows that sympathetic increasing prevalence of Pregnancy Induced Hypertension dominance is more during pregnancy as compared to non- (PIH)/Preeclampsia. pregnant (2.09±0.91 in pregnant and 1.04±0.65 in non-pregnant Aim: To measure HRV and urinary microalbumin excretion group). simultaneously in pregnant women. Conclusion: It was concluded that there is a neurogenic role Materials and Methods: In this hospital-based study, pregnant for the causation of microalbuminuria in pregnancy. As this women in 2nd and 3rd trimester were recruited along with age- condition predicts the development of pre-eclampsia/eclampsia matched controls. Their sympathetic activity and urinary in later pregnancy, all the methods targeting generalised stress albumin-creatinine ratio were recorded. The patients were reduction could be advised to all pregnant women during their followed till delivery to note progression to preeclampsia/ first visit. Keywords: Heart rate variability, Pregnancy induced hypertension, Sympathetic dominance, Urinary albumin creatinine ratio INTRODUCTION Sympathetic activation is commonly seen in early stages of healthy Pregnancy is a physiological state of haemodynamic changes. The pregnancy in spite of normally occurring reduced diastolic pressure glomerular filtration rate and renal blood flow rise markedly during [10]. Along with this finding, the sympathetic dominance is more pregnancy [1]. These changes in flow rate and permeability of prominent in pregnancy with PIH [11]. A Sudan based study has the glomerular basement membrane increase the urinary protein also found evidence for dominant cardiac sympathetic modulation excretion substantially, leading to microalbuminuria [2]. in pregnant women with pre-eclampsia [12]. Also, a recent study has verified that autonomic nervous system imbalance, as well In the general population, this urinary microalbumin estimation is a as insulin-resistance are impaired in PIH as compared to healthy good screening test for early detection of renal disease and may be pregnant women [13]. The clinical manifestations of PIH are said a marker for the presence of microvascular disease [3]. It is currently to be linked to placental ischaemia which releases cytokines into an indication of interventions, such as lowering of blood pressure circulation leading to endothelial dysfunction [14]. Also, as earlier even in the absence of hypertension or diabetes [4]. mentioned, microalbuminuria has been frequently reported in PIH. As albuminuria is one of the classical signs of pre-eclampsia, Keeping in mind these information, several questions are raised. Is if microalbuminuria is present in a symptom-free female during autonomic dysfunction in any way leading to placental ischaemia and pregnancy, it confirms that there are changes occurring in the renal microalbuminuria (as sympathetic activity causes vasoconstriction)? function and the patient may develop pre-eclampsia eventually Is sympathetic dominance a feature of all pregnancies or it has any [5]. Thus, early pregnancy levels of microalbuminuria can be specific relation with prediction of PIH? used as a predictor of pre-eclampsia [6]. All these physiological and pathological changes are associated with the dysfunction of So, authors undertook to analyse HRV and urinary microalbumin excretion simultaneously in pregnant women. This would throw light autonomic nervous system. In pre-eclamptic patients, a higher on the pathophysiology of the occurrence of microalbuminuria with excitability of sympathetic system has been noted [7]. In fact, in all respect to possible sympathetic overactivity. hypertensive individuals, sympathetic hyperactivity is a generalised phenomenon, irrespective of the heterogeneous clinical aspects MATERIALS AND METHODS that accompany a high blood pressure state [8]. This is a hospital-based cross-sectional and prospective study It has even been proposed that all the haemodynamic changes conducted in the Department of Biochemistry, Subharti Medical during pregnancy occur through autonomic control mechanisms College and Chhatrapati Sahuji Subharti Hospital, Meerut, Uttar [7]. Pre-eclampsia-related changes in the Autonomic Nervous Pradesh, India after obtaining ethical clearance from the Institutional System (ANS) based control of heart rate, including both ethical Committee. A total of 80 pregnant women (40 in 2nd trimester sympathetic and parasympathetic divisions can be detected by a and 40 in 3rd trimester) attending antenatal clinic along with 40 proper analysis of HRV. HRV is a measurement of the beat to beat matched controls were included in the study over a period of one fluctuation in the function of heart. It reflects an influence of ANS and half year (June 2015 to Dec 2016). Sample size was determined on heart rhythm [9]. keeping a-value at 0.05 and power of study 80%. 8 Journal of Clinical and Diagnostic Research. 2018 Dec, Vol-12(12): BC08-BC12 www.jcdr.net Inder Pal Kaur et al., Sympathetic Overactivity Predicts Microalbuminuria in Pregnancy Source population: Both second and third trimester subjects were All data are reported as mean±standard deviation/standard error of selected from the pregnant women attending the antenatal clinic of mean (mean±SD/SEM). Significance was considered when p-value a tertiary level northern Indian hospital. Consecutively, controls were was calculated to be less than 0.05. randomly selected from the vicinity after age matching (18-40 years; mean±SD- 25.79±4.15). RESULTS Subjects with acute anxiety, severe stress, previous history of The cases comprised of 80 pregnant women (40 in 2nd trimester and eclampsia, uncontrolled hypertension, diabetes mellitus, gestational 40 in 3rd trimester of pregnancy). Forty age-matched non-pregnant hypertension, gestational Diabetes Mellitus or any other endocrine/ women were also recruited for the study. [Table/Fig-1] shows autonomic disorders and patients suffering from any acute or the comparison of physiological parameters. The average blood chronic illness like renal failure, cardiovascular disease, and hepatitis pressure in the cases was 113.25±10.57 (systolic) and 71.19±8.19 were excluded from the study. (diastolic) which is comparable to the controls. So, all the cases As per the guidelines of National Kidney Foundation, spot were normotensive during the study. morning Urine measurement of Albumin to Creatinine Ratio The Microalbumin levels checked in the second trimester of pregnancy (UACR) was measured for proteinuria [15]. Spot midstream urine was 70.29±51.85 and in the third trimester were 58.71±36.15, sample was collected in a sterile container and stored at –20°C whereas in the control group it was 17.65±14.19. This showed that refrigerator with proper labels and seal (Parafilm) till further test. the levels of Microalbumin were found to be high in the pregnant Urinary Microalbumin was estimated using kit from VITROS 5.1 group and in them was higher in the 2nd trimester as compared to FS Chemistry system manufactured by Johnson and Johnson. the 3rd trimester (p<0.001). The urinary spot ACR showed values of The basic test principle utilises a turbidimetric inhibition based 84.48±52.61 in 2nd trimester, 72.35±50.29 in 3rd trimester, and only immune-assay technology. Urinary creatinine estimation was done 17.59±6.19 in the non-pregnant control group. This again implies after 21 times dilution with reagent-grade water as recommended that ACR is raised in pregnancy (p<0.001) [Table/Fig-2]. on Vitros 5.1 FS chemistry autoanalyser. All samples were stored for The next parameter studied was heart rate variability. This is not more than a month before analysis. Urinary Albumin Creatinine Ratio (UACR) was calculated using the following formula [16]: Cases (Mean±SD; Controls (Mean±SD; Variables p-value Range) n=80 Range) n=40 Age (years) 25.44±3.48 (19-36) 26.50±5.23 (21-38) 0.188 Height (cm) 156.24±4.83 (145-170) 154.65±5.45 (145-175) 0.107 To find out the status of cardiac autonomic nervous system, heart Weight (kg) 62.76±10.43 (38-98) 54.75±7.42 (38-67) <0.001** rate variability was recorded in the Physiology Department using SBP (mmHg) 113.25±10.57 (90-140) 111.00±11.36 (90-130) 0.286 RMS POLYRITE-D-Analog/PC based Polygraph/Physiograph. DBP (mmHg) 71.19±8.19 (60-100) 68.60±4.30 (60-76) 0.064 Experiment was done in a quiet room during which subjects were [Table/Fig-1]: Comparison of clinical variables in Cases vs Controls. made to lie down in a supine position. For recording of short-term SD: Standard deviation; DBP: Diastolic blood pressure; SBP: Systolic blood pressure
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