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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 7  |  Issue : 2  |  Page : 58-62

Renal function assessment by estimation of fractional excretion of sodium and magnesium in asphyxiated newborn


1 Department of Pediatric Nephrology, Chittagong Medical College, Chittagong, Bangladesh
2 Department of Pediatric Nephrology, Dhaka Shishu (Children) Hospital, Sher-e-Banglanagar, Dhaka, Bangladesh
3 Department of Pediatric Nephrology, National Institute of Kidney Diseases and Urology, Sher-e-Banglanagar, Dhaka, Bangladesh

Date of Submission10-Jan-2022
Date of Acceptance05-Feb-2022
Date of Web Publication22-Nov-2022

Correspondence Address:
Dr. Mohammed Maruf Ul Quader
Department of Pediatric Nephrology, Chittagong Medical College, 57 KB Fazlul Kader Road, Chittagong 4203
Bangladesh
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pnjb.pnjb_2_22

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  Abstract 

Background: Fractional excretion of magnesium (FEMg) is found to be the most sensitive index among fractional excretion of solutes to detect tubular damage in glomerulonephritis, although fractional excretion of sodium (FENa) is used to detect renal tubular dysfunction in perinatal asphyxia till date. Aim and Objective: The aim of this article is to assess the diagnostic performance of FENa and FEMg as renal function test in asphyxiated newborns. Materials and Methods: This cross-sectional study was conducted on 100 asphyxiated newborns in Dhaka Shishu (Children) Hospital, Bangladesh, over 1 year. Serum and urine creatinine, sodium, and magnesium were assessed in each patient; FENa and FEMg were calculated. Serum creatinine was regarded as gold standard for renal function. Results: FENa had 63.64% sensitivity, 100% specificity, 100% positive predictive value, 90.70% negative predictive value, and 92% accuracy. FEMg had 100% sensitivity, 66.67% specificity, 45.83% positive predictive value, 100% negative predictive value, and 74% accuracy. Receiver-operating characteristic curve revealed that area under the curve for FENa was 0.990 and for FEMg was 0.833. So, area under the curve for FENa was more than that of FEMg. Conclusion: FENa is better than FEMg in the assessment of renal function of asphyxiated newborns.

Keywords: Fractional excretion of magnesium, fractional excretion of sodium, perinatal asphyxia


How to cite this article:
Quader MM, Hanif M, Afroze S, Khan AH. Renal function assessment by estimation of fractional excretion of sodium and magnesium in asphyxiated newborn. Paediatr Nephrol J Bangladesh 2022;7:58-62

How to cite this URL:
Quader MM, Hanif M, Afroze S, Khan AH. Renal function assessment by estimation of fractional excretion of sodium and magnesium in asphyxiated newborn. Paediatr Nephrol J Bangladesh [serial online] 2022 [cited 2022 Dec 3];7:58-62. Available from: http://www.pnjb-online.org/text.asp?2022/7/2/58/361619




  Introduction Top


Perinatal asphyxia (PNA) is the simultaneous combination of both hypoxia and hypoperfusion,[1] responsible for multiorgan dysfunction. In PNA, the most frequent abnormality occurs in kidney (50%).[2] Hypoxic ischemic encephalopathy (HIE) cases experience 17.2% of renal failure.[3] Acute kidney injury (AKI) is reported to occur in 50–60% of neonates with severe birth asphyxia.[4]

Kidney is sensitive to oxygen deprivation, and renal insufficiency may occur within 24 h of asphyxia. It is an almost completely silent organ and remains so until renal function is severely impaired. The neonatal kidney has been described as “half way to acute renal failure” because of its physiological characteristics such as low glomerular filtration rate (GFR), decreased intercortical perfusion, decreased proximal tubular reabsorption of sodium, and plasma renin activity.[5] In PNA, estimation of blood urea and creatinine level does not actually reflect the degree of renal injury. Serum creatinine interpretation is complicated because maternal creatinine concentration significantly reflects on the serum creatinine concentration of the neonate within first 48 h of life. Urea concentration in plasma varies inversely with GFR. It is influenced by so many factors such as catabolic state and dehydration.[6] Urine volume measurement in neonates is cumbersome and time-consuming, which delays the appropriate prompt management. Moreover, normal urine output (nonoliguric AKI) is found in 60% of those with AKI secondary to asphyxia or drug toxicity.[4]

Hypoxia and hypoperfusion to the kidneys result in renal tubular cellular damage, and prolongation results in acute tubular necrosis, especially proximal tubular cells due to high metabolic activity and oxidative phosphorylation.[7] In neonates, acute tubular necrosis and acute renal failure are used interchangeably.[8] Tubular dysfunction can be predicted by urinary indices: specific gravity, osmolality, sodium, and urine/plasma creatinine. Fractional excretion of sodium (FENa) is used as an indicator of renal tubular dysfunction in asphyxiated newborns.[9] It indicates acute tubular necrosis,[10] but may not a good indicator of hypovolemia; moreover, it varies with gestational age. FENa >2.5% was found in 8% of healthy newborns.[11] Mohan and Pai[12] showed FENa is variable and not useful in distinguishing between renal and prerenal cause.

Nowadays, fractional excretion of magnesium (FEMg) is the newer approach to detect tubular function. A normal FEMg is usually associated with intact tubular structure, and an abnormally elevated FEMg is associated with tubular damage.[13] Clinically non-invasive FEMg is the most sensitive marker in detecting low-level tubular injury in humans and would lead to initiation of therapy at an early stage of renal disease when there is still an adequate renal function reserve.[14] FEMg was found to be the most sensitive index among fractional excretion of solutes (uric acid, sodium, calcium, phosphate, magnesium) to detect tubular damage in glomerulonephritis and diabetic nephropathy and used as a screening marker for early stage of chronic kidney disease. However, FEMg has never been observed in PNA. FEMg did not vary with post-conceptional age.[15] It is a very simple test to measure in a laboratory on a random urine specimen.[16]


  Materials and Methods Top


This cross-sectional study was conducted in Dhaka Shishu (Children) Hospital, Sher-e-Banglanagar, Dhaka, Bangladesh for 1 year. The general objective was to assess the diagnostic performance of FENa and FEMg as renal function test in asphyxiated newborns. Specific objectives were (a) estimation of serum creatinine in asphyxiated newborns, (b) estimation of FENa in asphyxiated newborns, (c) estimation of FEMg in asphyxiated newborns, and (d) comparison of the diagnostic performance of FENa with FEMg. Inclusion criteria were as follows: newborn with gestation ≥34 weeks, aged between 0 and 120 h with (a) history of failure to establish spontaneous respiration immediately after birth, (b) history of delayed cry/no cry at all after birth and/or history of requirement of resuscitation to sustain life after birth, (c) APGAR score ≤ 6 at 5 min, and (d) evidence of development of hypoxic ischemic encephalopathy. Exclusion criteria were as follows: (a) newborn with <34 weeks of gestational age; (b) newborn with congenital anomalies of kidney and urinary tract (CAKUT), congenital heart disease, and any visible anomaly; (c) history of maternal sedation; (d) history of antepartum hemorrhage; and (e) culture-proven sepsis. Informed written consent from legal guardian was taken. Detailed history and physical examination were done and recorded in the form of a questionnaire. Dhaka Shishu (Children) Hospital is solely a pediatric hospital, and no obstetric care is available. So inclusion was done on a referral note of a hospital and in-home delivery according to the statement of the attendant present during delivery. Female babies were put on a sterile self-adhesive urine collection bag and male babies on a sterile test tube for collection of urine. Five milliliters of voided spot urine was collected and sent for the analysis of urine sodium (Na), creatinine, magnesium (Mg). Two milliliters of blood was collected for serum creatinine, Na, and Mg and analyzed in the laboratory of Dhaka Shishu (Children) Hospital. Magnesium estimation was done by MG Flex R Reagent Cartridge, Cat. No., DF 57, Siemens Healthcare Diagnostic Ltd, 2008, UK patent number 717057.001.2004-04-07.

Formula for calculating FENa is as follows:



FENa >2.5% suggests established acute tubular necrosis or intrinsic renal failure.[17]

Formula for calculating FEMg is as follows:



Normal value is <2.2%.

FEMg ≥2.2% indicates tubulointerstitial damage or tubular dysfunction.[18]

Serum creatinine is regarded as gold standard for renal function. Serum creatinine 1.5 mg/dL (130 µmol/L) or more regardless of the rate of urine output was labeled as neonatal acute renal failure.[8] Ultrasonography (USG) of kidneys, ureters, and urinary bladder was done in every case to exclude CAKUT. Echocardiography was done in cases in which serum creatinine was found to be >130 µmol/L to exclude cardiac anomaly. Twenty-one cases were excluded from the study after getting positive blood culture (10), CAKUT (7) in USG, and congenital heart disease(4) by echocardiography. Finally, 100 neonates were studied. Then sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated, and receiver-operating characteristic (ROC) curve was constructed for FENa and FEMg.


  Results Top


Most of the cases (62%) were 34–37 weeks of gestational age. [Table 1] shows diagnostic performance of FENa and found 63.64% sensitivity, 100% specificity, 100% positive predictive value, 90.70% negative predictive value, and 92% accuracy. [Table 2] shows diagnostic performance of fractional excretion of magnesium (FEMg) and found 100% sensitivity, 66.67% specificity, 45.83% positive predictive value, 100% negative predictive value, and 74% accuracy. ROC curve revealed that area under the curve for FENa was 0.990 and FEMg was 0.833 [Figure 1] and [Figure 2]. So, area under the curve for FENa was more than that of FEMg [Table 3].
Table 1: Diagnostic performance of FENa (n = 100)

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Table 2: Diagnostic performance of FEMg (n = 100)

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Figure 1: ROC curve of FENa in the assessment of renal function of asphyxiated newborns

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Figure 2: ROC curve of FEMg in the assessment of renal function of asphyxiated newborns

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Table 3: Comparison between area under the curve for FEMg and FENa in the assessment of renal function of asphyxiated newborns

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  Discussion Top


PNA is one of the most common causes of neonatal mortality and morbidity. Neonatal asphyxia is the most common cause of neonatal acute renal failure.[19] So, timely diagnosis and its management are very crucial. Essential characteristics of PNA are defined jointly by the American College of Obstetricians and Gynecologist (ACOG) and American Academy of Pediatrics (AAP).[20] Bangladesh Neonatal Forum has given more simpler definition: asphyxia is failure on the part of the baby to start breathing spontaneously or maintain regular breathing after birth. If the baby is asphyxiated she/he may (1) gasp, (2) breath very irregularly, and (3) may not breath at all.[21] PNA is graded by the APGAR score.[22]

A total of 100 cases with gestation ≥34 weeks were included in this study according to the inclusion criteria. This was a cross-sectional study conducted over a period of 1 year in Dhaka Shishu (Children) Hospital, which is the largest children hospital of the country.

Nephrogenesis is not completed until about 34 weeks of gestation.[4] Renal functions are reasonably mature and stable by 34 weeks of gestation. So, babies ≥34 weeks were included in this study. In this study, 62% of the babies were within 34–37 weeks. But in the study done in Dhaka Shishu (Children) Hospital, 80% of the cases were term. Moderately asphyxiated babies were 53% and severely asphyxiated babies were 30%.[9]

Male (56%) predominance was found in this study. Exact cause is not clear but possible explanation is early referral of the male neonate.

Roberts et al.[23] observed 19% acute renal failure in asphyxiated neonates, but more was observed by Gupta et al.[5] (47.1%) and Aggarwal et al.[11] (68%), as they included babies with more severe birth asphyxia. Most of the studies were done in a tertiary level teaching hospital where all deliveries took place. So, it can be assumed that APGAR scoring, resuscitation, and referral note were appropriate for enrolment. Experience of renal failure was observed more in severely asphyxiated neonates than those with milder asphyxia.[11] But in this study 22% observed acute renal failure. This study included cases which were referred mostly from different parts of the country. Inclusion was done according to the referral note of the hospital, clinic, or attendant’s statement in-home delivery, which may be inappropriately estimated. Most of the referred babies were locally unmanageable asphyxiated babies.

Timed urine collection for the estimation of FENa, FEMg, and urine volume (mL/kg/h) measurement was not done because it was not necessary.[24] Rahman et al.[9] and Gupta et al.[5] did not find any significant difference in urine output between control and asphyxiated neonates. Urine output did not correlate even with severity of asphyxia.[5]

Among the cases, 48% had FEMg >2.2% which included all the cases of acute renal failure. Diagnostic performance of FEMg in this study revealed 100% sensitivity, 66.67% specificity, 45.83% positive predictive value, 100% negative predictive value, and 74% accuracy. Among fractional excretion of solutes (uric acid, sodium, calcium, phosphate, magnesium), FEMg appeared to be the most sensitive index of tubular damage.[25] So, this study revealed that FEMg had no false negativity but high false positivity and may over estimate the renal function of asphyxiated newborns.

Magnesium is the second most abundant intracellular cation next to potassium. Chronic ischemic injury secondary to reduction of peritubular capillary blood flow is responsible for the insult at the thick ascending loop of Henle where maximum magnesium reabsorption occurs. In the presence of hypermetabolic state as well as the defective effective circulatory blood volume catabolic breakdown of magnesium from the storage or substrate in the tubular epithelium increased and eventually renal magnesium wasting occurs.[25] So, FEMg will increase above the normal range when tubular damage occurs.[26] Gheissari et al.[27] found FEMg as a marker for tubular dysfunction in children. It can predict interstitial nephropathy.[28]

FENa found >2.5% in 14% of the cases, which is similar to Rahman et al.’s study.[9] Diagnostic performance of FENa in the study revealed 63.64% sensitivity, 100% specificity, 100% positive predictive value, 90.70% negative predictive value, and 92% accuracy. All cases showed that FENa >2.5% also had acute renal failure. So, this study revealed that FENa had very low false negativity and no false positivity. FENa increased with increasing severity of asphyxia and HIE staging.[29]

Moreover, ROC curve showed that area under the curve for FENa was 0.990 and FEMg was 0.833. Both the tests had good diagnostic performance but area under the ROC curve is more in FENa. So, diagnostic performance of FENa was found to be better than that of FEMg.

In this study, some cases had received aminoglycosides such as gentamicin or amikacin, which is nephrotoxic. But it was not a confounder, because they received only one to three doses before admission to Dhaka Shishu Hospital. The immature kidney appears to be less susceptible to aminoglycoside toxicity than that of the adult. Nephrotoxicity occurs in newborns on prolonged administration of aminoglycoside.[8] Aminoglycoside is not the confounder in determining indices of renal tubular function in PNA.[30] Moreover, probable confounders such as sepsis, CAKUT, and congenital heart disease were excluded. Further studies may be done on inborn asphyxiated cases with appropriate APGAR scoring to observe the extent of AKI as well as to assess the performance of FENa and FEMg.


  Conclusion Top


FENa is better than FEMg in the assessment of renal function of asphyxiated newborns.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Papile L, Adcock LM Perinatal asphyxia. In: Cloherty JP, Eichenwald ER, Stark AR, editors. Manual of Neonatal Care. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2008. p. 523.  Back to cited text no. 2
    
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Sharon PA Clinical evaluation and management: Acute renal failure. In: Avner ED, Harmon WE, Niaudet P, editors. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 1233-46.  Back to cited text no. 7
    
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Rahman MK, Islam MN, Siddika M, Bhuiyan KJ, Chowdhury MA Assessment of renal function by estimation of fractional excretion of sodium in asphyxiated newborns. Mymensingh Med J 2012;21: 516-21.  Back to cited text no. 9
    
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Langlois V Laboratory evaluation at different ages. In: Geary DF, Schaefer F, editors. Comprehensive Pediatric Nephrology. Philadelphia: Mosby Elsevier; 2008. p. 44.  Back to cited text no. 10
    
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Aggarwal A, Kumar P, Chowdhary G, Majumdar S, Narang A Evaluation of renal functions in asphyxiated newborns. J Trop Pediatr 2005;51:295-9.  Back to cited text no. 11
    
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Mohan PV, Pai PM Renal insult in asphyxia neonatorum. Indian Pediatr 2000;37:1102-6.  Back to cited text no. 12
    
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Joyce WU, Carter P Magnesium the forgotten electrolyte. Aust Prescr 2007;30:102-5.  Back to cited text no. 16
    
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Wong W Kidney problem in neonate. In: Chiu MC, Yap HK , editors. Practical Paediatric Nephrology—An Update of Current Practices. Hong Kong: Medicom Limited; 2005. p. 217.  Back to cited text no. 17
    
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[PUBMED]  [Full text]  
20.
ACOG Committee Opinion. Inappropriate uses of the term fetal distress and birth asphyxia. Int J Gynaecol Obstet 1998;61:309-10.  Back to cited text no. 20
    
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Roberts DS, Haycock GB, Dalton RN, Turner C, Tomlinson P, Stimmler L, et al. Prediction of acute renal failure after birth asphyxia. Arch Dis Child 1990;65:1021-8.  Back to cited text no. 23
    
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Futrakul N, Yenrudi S, Sensirivatana R, Watana D, Laohapaibul A, Watanapenphaibul K, et al. Peritubular capillary flow determines tubulointerstitial disease in idiopathic nephrotic syndrome. Renal Fail 2000;22:329-35.  Back to cited text no. 26
    
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Gheissari A, Andalib A, Labibzadeh N, Modarresi M, Azhir A, Merrikhi A Fractional excretion of magnesium (FEMg), a marker for tubular dysfunction in children with clinically recovered ischemic acute tubular necrosis. Saudi J Kidney Dis Transpl 2011;22:476-81.  Back to cited text no. 27
    
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Noiri C, Shimizu T, Takayanagi K, Tayama Y, Iwashita T, Okazaki S, et al. Clinical significance of fractional magnesium excretion (FEMg) as a predictor of interstitial nephropathy and its correlation with conventional parameters. Clin Exp Nephrol 2015;19:1071-8.  Back to cited text no. 28
    
29.
Karlo J, Bhat BV, Koner BC, Adhisivam B Evaluation of renal function in term babies with perinatal asphyxia. Indian J Pediatr 2014;81:243-7.  Back to cited text no. 29
    
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