|Year : 2015 | Volume
| Issue : 5 | Page : 941-946
|Microalbuminuria - A better marker in hypertensive disorders of pregnancy
Ruby P Babu1, Alap Christy1, Anupama Hegde1, Poornima Manjrekar1, Maria Joseph2
1 Department of Biochemistry, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
2 Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
Click here for correspondence address and email
|Date of Web Publication||7-Sep-2015|
| Abstract|| |
To assess the role of microalbuminuria in pre-eclampsia (PE) as a diagnostic marker, we studied 40 PE cases and 40 normotensive controls at 24 ± 4 weeks of gestation in women 20-35 years of age. The patients with PE had significant microalbuminuria in comparison with the controls, in addition to deranged renal function tests. The receiver operating characteristic curve showed that microalbuminuria had the highest sensitivity (100%) and good specificity (77.6%). Microalbuminuria had the highest area under the curve (0.869) for both diagnosis of PE and renal function assessment. Microalbuminuria also had a good correlation with systolic blood pressure in the cases with mild grades of renal dysfunction. Microalbuminuria is a specific marker in PE and it also helps to assess the renal function status. Therefore, microalbuminuria may be used in the early diagnosis and management of PE patients in order to reduce the immediate and long-term complications.
|How to cite this article:|
Babu RP, Christy A, Hegde A, Manjrekar P, Joseph M. Microalbuminuria - A better marker in hypertensive disorders of pregnancy. Saudi J Kidney Dis Transpl 2015;26:941-6
|How to cite this URL:|
Babu RP, Christy A, Hegde A, Manjrekar P, Joseph M. Microalbuminuria - A better marker in hypertensive disorders of pregnancy. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2022 Dec 4];26:941-6. Available from: https://www.sjkdt.org/text.asp?2015/26/5/941/164574
| Introduction|| |
Pregnancy-induced hypertensive (PIH) disorders encompasses a whole spectrum of pathologies and disease states such as transient gestational hypertension, pre-eclampsia (PE), chronic arterial hypertension (CAH), PE superimposed on CAH, eclampsia and HELLP syndrome. 
PIH contributes significantly to the maternal mortality, premature birth, intrauterine growth retardation (IUGR) and perinatal mortality. 
PE is observed in 10-20% of pregnant women. It is defined as hypertension of ≥140/90 mm Hg associated with proteinuria (≥300 mg/24 h or ≥1+/ran dom sample dipstick test), with onset after 20 weeks of gestation, persisting up to 12 weeks after delivery. 
The diagnostic work-up of PE patients includes renal function assessment by measurement of parameters such as proteinuria, urea, creatinine, uric acid, creatinine clearance, blood urea nitrogen (BUN), albumin and 24-h urinary protein. Liver enzymes, bilirubin and coagulation screening are performed to rule out hepatic involvement (HELLP syndrome). Other parameters such as serum magnesium and calcium are also measured. , Radiological imaging to evaluate the fetal development and utero-placental circulation is also a part of the assessment. 
Proteinuria is a defining dysfunction of PE and repeated urinalysis to screen for the condition is part of the standard antenatal care. It has been proposed to be an indicator of both the severity of disease and the prediction of its outcome. 
Microalbuminuria, albuminuria rates of 30-300 mg/g of creatinine and reduced estimated glomerular filtration rate (eGFR) have been proposed as useful integrated markers of sub-clinical target organ damage and renal endothelial injury resulting from local or systemic vascular damage. ,
Studies have shown that the presence of microalbuminuria earlier in pregnancy is associated with an increased risk of development of PE and severe adverse maternal and fetal outcome in PE. ,
The aim of this study was to assess the role of microalbuminuria as a diagnostic marker in PE and as a parameter for assessing renal function in this disease.
| Materials and Methods|| |
We conducted this study at the Kasturba Medical College Hospital (KMCH), Ambedkar Circle, KMCH Attavar and Government Wenlock Hospital, Mangalore from June 2013 to July 2013. Ethical clearance was obtained from the scientific and ethical committee of the institution. Informed consent was obtained from all the subjects.
We studied 40 normotensive pregnant women as controls and 40 pregnant women between 20 and 35 years of age were selected at 24 ± 4 weeks of gestation and had PIH diagnosed by the accepted criteria of the Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy with a blood pressure of >140/90 mm Hg and proteinuria (>300 mg/24-h).
Cases of proteinuria due to other causes such as chronic hypertension, urinary tract infection, established renal diseases, diabetes mellitus, fever and acute inflammatory conditions and trauma were excluded from the study. Obstetric history including the last menstrual period, parity, period of gestation, previous obstetric history, complications and adverse outcomes of the patient were documented. Relevant medical history of the patients was also taken to rule out other causes of proteinuria. Based on these details, subjects meeting the exclusion criteria were dropped from the study.
Values of the patients' serum creatinine measured by the Jaffe's method, serum urea measured by the urease method and uric acid measured by the uricase method were collected from the hospital laboratory data. Midstream early morning urine samples were collected from the patients and measurement of microalbuminuria was performed by the immune-turbidometric method in the semiautoanalyser at the Department of Biochemistry, Center for Basic Sciences, KMC Bejai. eGFR was calculated by the four-variable Modified Diet and Renal Disease (MDRD) formula:
eGFR (mL/min per 1.73 m 2 = 1.86 × (P Cr) -1.154 × (age) -0.203 . Multiply by 0.742 for women.
Blood pressure was recorded in the sitting position on two occasions about one week apart.
| Statistical analysis|| |
Data were analyzed by IBM SPSS version 20 software. Student's t-test was performed to compare the renal markers and PE markers between the cases and the controls. The sensitivity and specificity of microalbuminuria were compared with the measured parameters by applying the receiver operating characteristics (ROC) curve. The correlation between microalbuminuria and systolic blood pressure in patients with mild-grade renal dysfunction was performed by Pearson's correlation analysis. The data were expressed as mean (standard deviation) and percentages. P-value <0.05 was considered to be statistically significant.
| Results|| |
[Table 1] shows the baseline characteristics of the normotensive and the PE patients. The average age, period of gestation and parity status were not statistically different between the two groups. [Table 2] shows the comparison of the parameters of PE such as uric acid, proteinuria and microalbuminuria and renal function markers and blood pressures between the two study groups, and all the parameters showed a statistically significant difference between the study group and the controls. Microalbuminuria (47.41 ±1 6 mg/L) was significantly higher in the patients with PE compared with the control group, although it had no linear correlation with the grades of proteinuria.
|Table 2: Comparison of the serum, urinalysis and blood pressures between the normotensive controls and pre-eclampsia (PE) patients.|
Click here to view
[Figure 1] and [Table 3] and [Table 4] display the ROC curves of all the PE parameters in the study group and the area under the curve (AUC), respectively.
|Figure 1: The receiver operating characteristics (ROC) curve analysis for various markers of pre-eclampsia (PE) and renal markers with microalbuminuria.|
Click here to view
|Table 3: Area under the curve for renal markers in pre-eclampsia (PE) in the study patients.|
Click here to view
|Table 4: Area under the curve for the pre-eclampsia (PE) markers in the study patients.|
Click here to view
[Table 5] shows the comparison of sensitivity and specificity of the various renal function parameters in PE. The sensitivity of microalbumin was 100% and the specificity was 77.6%, both being the highest amongst all renal function markers except creatinine, which had a higher specificity.
|Table 5: Sensitivity and specificity of renal markers for pre-eclampsia (PE) in the study patients.|
Click here to view
[Table 6] shows the comparison of sensitivity and specificity of microalbuminuria with other markers of PE, such as uric acid and proteinuria. Microalbuminuria had the highest sensitivity and specificity.
[Table 7] shows the correlation between the systolic blood pressure and the markers of PE in patients with low eGFR (<90 mL/h). The strength of association for microalbuminuria was good, but it was stronger for proteinuria. The levels of uric acid also had a strong association with the systolic blood pressure in comparison with the microalbuminuria.
|Table 7. Correlations of the different parameters with SBP in patients with eGFR <90.|
Click here to view
| Discussion|| |
The results of our study showed significant differences in all the parameters between the cases and the controls, as was expected. There was sig-nificant microalbuminuria in patients of PE (47.41 ± 16 mg/L) compared with the normotensive patients (13.8 ± 5.6 mg/L).
The presence of microalbuminuria in PE is due to the underlying pathology of the disease. , The mechanism for proteinuria in PE is not well understood. The glomerular basement membrane and podocytes typically appear normal. , Layfette et al  stated that the impaired charge selectivity rather than the filtration diaphragm-related impairment of size selectivity is responsible for the heavy microalbuminuria.
In PE, the glomerular barrier is certainly altered and there is an increased excretion of protein, including albumin. Generally, urine from PE has demonstrated a poor selectivity and has not differed significantly from other forms of primary renal disease. Glomerular proteins of intermediate size, such as albumin, have been identified alone or in combination with varying degrees of tubular proteins, such as β2-microglobulin, reflecting the tubular damage that can occur in severe PE. ,,
When total protein excretion exceeds 1 g/24 h, tubular protein reabsorption will be saturated and individual proteins excretion rates will be related to their molecular weights.  This non-selective proteinuria does not help in assessing whether it was due to glomerular damage or tubular dysfunction or both. Measurement of microalbuminuria on the other hand helps to exclude non-specific collateral damage.
Bar et al  described a phase of microalbuminuria that preceded clinical proteinuria and that this test has some predictive value for severe disease. They also suggest that the accepted definition of gestational proteinuria should be reconsidered.  Furthermore, microalbuminuria preceded the development of hypertension in other studies; hence, it is a good predictor of PIH. , Microalbuminuria is also used in the evaluation to rule out preexisting chronic hypertension.  However, its role in established PE is not well defined.
The ROC curve and sensitivity and specificity comparison between the micoralbuminuria and other PE markers showed that it is a good marker in PE and that it has the highest sensitivity and specificity. One study  concluded that albumin excretion rate appeared to be the best predictive test in comparison with uric acid and fibronectin for PE in hypertensive pregnant women, giving a higher positive predictive value and specificity (87.5% and 98.9%, respectively). In another study, microalbuminuria had a specificity of 98.9% when compared with serum uric acid and creatinine as a diagnostic marker for hypertensive disorders in pregnancy.  Unlike microalbuminuria, proteinuria measured by simple techniques is not sensitive or specific and is not predictive of adverse outcomes, and delivery management should not be based on protein excretion alone. 
In PE, variable degrees of renal insufficiency are associated with a characteristic glomerular lesion, "glomerular endotheliosis." ,
In our study, the patients with PE showed obvious signs of renal damage by an elevated serum urea, creatinine and low eGFR in comparison with the normotensive group. Studies show that early detection and treatment of kidney disease can slow, halt or even reverse its progression. ,
In our study, microalbuminuria was found to have a significant correlation with systolic blood pressure in the hypertensive group. Microalbuminuria may correlate more closely with other clinical measurements of disease severity as it may more accurately reflect the glomerular dysfunction associated with the glomerular endotheliosis of PE. 
Urine microalbumin did not correlate with mild renal dysfunction, that is cases with eGFR <90 mL/min. Microalbuminuria and eGFR are two independent risk factors and are complementary when it comes to assessing renal status.  In population studies, no correlation between albuminuria and GFR has been detected. 
We conclude that our study showed that microalbuminuria is a good diagnostic marker for PIH, although it may not be preferred for grading its severity. It is also a better marker of renal dysfunction in PIH compared with the established markers. Microalbuminuria evaluation in the second trimester in high-risk patients can serve as a sensitive indicator of renal function.
Conflict of interest: None declared.
| References|| |
Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000;183:S1-22.
Anand S, Kirshnanand. Perinatal outcome in growth retarded babies born to normotensive and hypertensive mothers: A prospective study. Peoples J Sci Res 2012;5:24-6.
Cunningham FG, Leveno KJ, Bloom SL, Hauth J, Gilstrap LC, Wenstrom KD, eds. Hypertensive Disorders in Pregnancy, Williams Obstetrics. 22 nd
ed. New York: McGraw-Hill;2005. p. 761-808.
Maybury H, Waugh J. Proteinuria in pregnancy: Just what is significant? Fetal Matern Med Rev 2004;16:71-95.
Verdecchia P, Reboldi GP. Hypertension and microalbuminuria: the new detrimental duo. Blood Press 2004;13:198-211.
Van de Wal RM, Voors AA, Gansevoort RT. Urinary albumin excretion and the renin-angiotensin system in cardiovascular risk management. Expert Opin Pharmacother 2006;7:2505-20.
Chua S, Redman CW. Prognosis for preeclampsia complicated by 5 g or more of proteinuria in 24 hours. Eur J Obstet Gynecol Reprod Biol 1992;43:9-12.
North RA, Taylor RS, Schellenberg JC. Evaluation of a definition of pre-eclampsia. Br J Obstet Gynaecol 1999;106:767-73.
Davison, JM. Renal function during normal pregnancy and the effect of renal disease and pre-eclampsia. In: Andreucci VE, edr. The Kidney in Pregnancy. Boston: Martinus Nijhoff; 1986. p. 65-80.
Sanchez-Ramos L, Briones DK, Kaunitz AM, Delvalle GO, Gaudier FL, Walker CD. Prevention of pregnancy-induced hypertension by calcium supplementation in angiotensin II-sensitive patients. Obstet Gynecol 1994;84:349-53.
AbdAlla S, Lother H, el Massiery A, Quitterer U. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med 2001;7:1003-9.
Lafayette RA, Druzin M, Sibley R, et al. Nature of glomerular dysfunction in pre-eclampsia. Kidney Int 1998;54:1240-9.
Hladunewich M, Karumanchi SA, Lafayette R. Pathophysiology of the clinical manifestations of preeclampsia. Clin J Am Soc Nephrol 2007;2:543-9.
Winkler U, Lison AE, Seitzer B, Niedner W. Urinary protein patterns for early detection of preeclampsia. Contrib Nephrol 1988;68:227-9.
Quaas L, Wilhelm C, Klosa W, Hillemanns HG, Thaiss F. Urinary protein patterns and EPH-gestosis. Clin Nephrol 1987;27:107-10.
Bar J, Hod M, Erman A, et al. Microalbuminuria as an early predictor of hypertensive complications in pregnant women at high risk. Am J Kidney Dis 1996;28:220-5.
Sonagra A, Biradar S, Dattatreya K, Murthy DS. Microalbuminuria in women with gestational hypertension. Int J Med Sci Public Health 2013;2:212-6.
Misiani R, Marchesi D, Tiraboschi G, et al. Urinary albumin excretion in normal pregnancy and pregnancy-induced hypertension. Nephron 1991;59:416-22.
Sibai BM. Hypertension in pregnancy. In: Gabbe SG, Niebyl JR, Simpson JL, (eds). Obstetrics: normal and problem pregnancies. 5 th
edn. Churchill Livingston, New York:1996. pp. 935-96.
Paternoster DM, Stella A, Mussap M, Plebani M, Gambaro G, Grella PV. Predictive markers of pre-eclampsia in hypertensive disorders of pregnancy. Int J Gynaecol Obstet 1999;66: 237-43.
Kanagasabai S. Biochemical markers in the prediction of pre-eclampsia, are we there yet? Internet J Gynecol Obstet 2009;14:1-7.
Airoldi J, Weinstein L. Clinical significance of proteinuria in pregnancy. Obstet Gynecol Surv 2007;62:117-24.
Koroshi A. Microalbuminuria, is it so important? Hippokratia 2007;11:105-7.
Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 2000;49:1399-408.
MacIsaac RJ. Albuminuria versus GFR as Markers of Diabetic CKD Progression: A KDIGO Controversies Conference Report Kidney International 2012;80:17-28.
Basi S, Fesler P, Mimran A, Lewis JB. Microalbuminuria in type 2 diabetes and hypertension: a marker, treatment target, or innocent bystander? Diabetes Care 2008;31 Suppl 2: S194-201.
Department of Biochemistry, Kasturba Medical College, Center for Basic Sciences, Mangalore - 575 004
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
|This article has been cited by|
||Association between two common environmental toxicants (phthalates and melamine) and urinary markers of renal injury in the third trimester of pregnant women: The Taiwan Maternal and Infant Cohort Study (TMICS)
| ||Hui-Ju Tsai, Fu-Chen Kuo, Chia-Fang Wu, Chien-Wen Sun, Chia-Jung Hsieh, Shu-Li Wang, Mei-Lien Chen, Hui-Min Hsieh, Yun-Shiuan Chuang, Ming-Tsang Wu |
| ||Chemosphere. 2021; 272: 129925 |
|[Pubmed] | [DOI]|
||Maternal Levels of Perfluoroalkyl Substances (PFAS) during Early Pregnancy in Relation to Preeclampsia Subtypes and Biomarkers of Preeclampsia Risk
| ||Paige A. Bommarito, Kelly K. Ferguson, John D. Meeker, Thomas F. McElrath, David E. Cantonwine |
| ||Environmental Health Perspectives. 2021; 129(10) |
|[Pubmed] | [DOI]|
||Pre-eclampsia is associated with later kidney chronic disease and end-stage renal disease: Systematic review and meta-analysis of observational studies
| ||Raphaela Costa Ferreira, Marilene Brandão Tenório Fragoso, Micaely Cristina dos Santos Tenório, João Victor Farias Silva, Nassib Bezerra Bueno, Marília Oliveira Fonseca Goulart, Alane Cabral Menezes de Oliveira |
| ||Pregnancy Hypertension. 2020; 22: 71 |
|[Pubmed] | [DOI]|
| Article Access Statistics|
| Viewed||5731 |
| Printed||38 |
| Emailed||0 |
| PDF Downloaded||631 |
| Comments ||[Add] |
| Cited by others ||3 |