Original Article Acute Kidney Injury; Shrestha NJ et al.

! !

Prevalence of Acute Kidney Injury in Patients with Perinatal

Asphyxia in Tertiary Hospital
Nisha Jyoti Shrestha1, Kalpana Upadhaya Subedi1, Shristy Shakya2 and
Saroja Adhikari3
1Department of Paediatrics, National Academy of Medical Sciences, Kathmandu, Nepal
2Department of Neonatology, Paropakar Maternity and Women’s Hospital, Kathmandu, Nepal
3Saroja Adhikari, Analyst , Digital Data System for Development, Kathmandu, Nepal

Correspondence:
Nisha Jyoti Shrestha ABSTRACT
Department of Paediatrics
National Academy of Medical Sciences Introduction: Perinatal asphyxia has multisystem involvement,
Kathmandu, Nepal kidneys are most frequently affected.This study was conducted to
E-mail: [email protected]
determine the relation between severity of Hypoxic Ischaemic
Encephalopathy (HIE) with acute kidney injury in term neonates.

Methods: Retrospective study was done over a period of six

months (Sept 2016 to Feb 2017) at Department of Neonatology of
DOI:10.3126/jnps.v39i2.27983 a tertiary level maternity hospital. Total 98 cases of Perinatal
Submitted on: 2020-03-09 asphyxia cases which were diagnosed with certain degree of HIE
Accepted on: 2020-04-15
were evaluated for its relation with renal involvement in different
stage of HIE.

Results: Out of 98 cases of perinatal asphyxia, HIE I was 21%,

HIE II was 69% and HIE III was 10%, among which 72% cases
had some degree of renal problem. seventy two cases had renal
Acknowledgements: None
problem, oliguric cases were 41 (57%) among which 33% case
had persistent symptoms and associated renal function
Funding: Nil
deterioration. Among 42 cases of deranged RFTs, 40% of cases
Conflict of Interest: None declared
has persistently deranged RFTs. In comparison to HIE II in HIE
Permission form IRB: Yes III, 22% of cases had one time derangement of RFTs and 33%
cases had at least one observation of oliguria, while remaining
45% cases had persistent deterioration of RFTs and urine output,
suggesting that progression in HIE stage has significant
association with renal dysfunction (p < 0.05). More than half of
the cases of HIE III had mortality while 20.3% of HIE II cases had
mortality, indicating that the mortality is highly significant with
higher HIE grade (p < 0.05).

Conclusions: Renal involvement is very common in cases of

To cite this article: Shrestha NJ, Subedi perinatal asphyxia, and severity of renal involvement increases as
KU, Shakya Shristy, Adhikari Saroja.
Prevalence of Acute Kidney Injury in
the HIE grading increases.
Patients with Perinatal Asphyxia in
Tertiary Hospital. J Nepal Paediatr Soc. Key words: : acute kidney injury; HIE; Oliguria; perinatal
2019;39(2):109-15. asphyxia

This work is licensed under creative common attribution 3.0 license

J Nepal Paediatr Soc Vol 39 Issue 2 May-Aug 2019 !109

 Original Article Acute Kidney Injury; Shrestha NJ et al.
! !
INTRODUCTION All asphyxiated (as per WHO definition) neonates
Perinatal asphyxia (PA) has multi-organ were selected as cases. Preterm cases, and the cases
involvement with multiple complications in the with incomplete data were excluded from the study.
neonatal period and beyond. Incidence of perinatal Variables such as gestational age, birth weight,
asphyxia is reported as 1 to 1.5% at various centres. perinatal history, examination findings were
In our country Nepal, perinatal asphyxia is the third recorded in predesigned proforma.
commonest cause for neonatal mortality, and also
All the cases had first renal function tests drawn
the most preventable cause to decrease neonatal after 48 hours of life. Under aseptic precautions, 3
mortality.1 ml blood was drawn and evaluated for blood urea
During the event of perinatal asphyxia most of the (Enzymatic Colorimetric Test), serum creatinine
organs are involved and damaged due to hypoxia (Jaffe’s test) and serum electrolytes (Calorimetric
and ischemia. The most affected organs are the method)
kidneys in 50% followed by brain in 28%, Results were recorded in the proforma. Daily vital
cardiovascular system (CVS) in 25% and lungs in
signs, occurrence of seizures, urine frequency was
23% cases.2 It is known that kidneys are very also noted in proforma. Abnormal creatinine was
delicate and sensitive to hypoxia, renal considered when serum creatinine was elevated two
insufficiency occurs within 24 hours of a hypoxic standard deviations above mean value for term
ischemic event. If the hypoxia and ischemia is
gestation or rising 0.3 mg/dL/day.2
prolonged, that event causes irreversible cortical
necrosis.2-4 Urine output data were extracted from nursing
records. Impaired urine output was considered if
In the cases with brain involvement, a stable
urine output was < 1 ml/kg/hr in catheterised
biochemical environment is utmost important. So,
children and less than six wet nappies in un-
to facilitate appropriate fluid and electrolyte catheterized children (beyond 12 hrs of life).
management, early recognition of renal
involvement is essential in Hypoxic Ischaemic IBM SPSS Version 20 was used to analyse the data,
Encephalopathy (HIE) cases.2,4 In neonates it is frequency and cross tabulation and Fisher exact t
very difficult to diagnose or to recognise of renal test was used to see the significant association
failure in initial state. It is mainly due to influence among variables. P value of < 0.05 was considered
of maternal biochemical parameters and poorly significant.
established biochemical parameters in this age
group.2,4 RESULTS
There were total 98 cases of PA during the six
It is well recognised that PA is one of the
months study period. The ratio of male:female was
commonest cause of newborn death in our country,1
1.45:1. The pie-chart in Figure 1 indicates that out
though survival percentage is better than before,
associated organ involvement determines the of 98 cases of PA with HIE, 21% had HIE grade I,
quality of life beyond neonatal period. Thus, we 69% grade II HIE, and 10% had Grade III. Table 1
performed this study to determine the occurrence of shows that among the cases, 71% had one minute
renal involvement in PA and to correlate the APGAR ≤ 3, only 17% of cases had five minute
severity of renal involvement with HIE grading of APGAR ≤ 3, and 77% had five minutes APGAR
asphyxiated neonates. 4-6. In our study, 6% of the cases showed good
Apgar at five minutes of life but were still included
METHODS in cases due to consistent finding of PA in physical
A retrospective study was conducted for a period of examination and laboratory findings like ABG.
six months, in a tertiary level referral hospital of Among 98 cases, mean one minute APGAR score
Kathmandu, Nepal, from 2016 Sept to 2017 Feb, was 2.85 ± 1.18 SD and mean 5 minute APGAR
where 98 term PA cases born with APGAR score score was 4.80 ± 1.3SD.
< 3/10 in 1 min and < 7/10 in 5 mins were
analysed.

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 Original Article Acute Kidney Injury; Shrestha NJ et al.
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Table 1. Frequency table of the score of APGAR

Score APGAR
1 minute 5 minute
Frequency % Frequency %
1-3 70 71 17 17
4-6 28 29 75 77
7 - 10 0 0 6 6
Table 1. Descriptive statistics of HIE grade Total 98 100 98 100

The cross-tabulation ( Table 2) of HIE grade and Table 4 shows that the percentage of mortality
APGAR one minute shows that the cases of HIE increases with increase in the level of HIE grade. It
are evenly distributed among various scores, and it shows that more than half of the cases of HIE III
represents that there is not a significant association suffered mortality i.e. 55.6%. There is only one
between the low one minute APGAR score and case of mortality among 20 cases of HIE I while
HIE grades. 20.3% of HIE II cases suffered mortality. Table also
indicates that the mortality is highly significant
Table 3 represents the score among the HIE grade with HIE grade.
of the cases of APGAR 5 min. The results show
that there is no cases of score 1 in APGAR five The contingency table 5 shows that out of 20 cases
minutes. Out of 20 cases of HIE I, 95% cases have of HIE I, only 15% cases have renal involvement
score 4-6/10. In HIE II, 14.5% had 1-3 APGAR and but in total nine cases of HIE III, renal involvement
78% had 4-6/10 APGAR. 78% of HIE cases had is seen in all cases. Similarly, 87% cases of HIE II
APGAR of 4-6/10. This represents that there is have renal involvement. Table also indicates that
significant association between the low five minute the involvement of renal is high as the HIE Grade
APGAR score and HIE grades. Out of 98 HIE increases, and this is statistically significant with p
cases 79.6% survived and 20.4% died during value is 0.00 (< 0.05).
course of treatment. Mortality pattern among all
In the crosstab (Table 6) of HIE grade in four
three grades of HIE are shown in Table 4.
categories shows that, out of 98 HIE cases 31 have
deranged urea/creatinine only, 20 have decreased

Table 2. Cross-tabulation of APGAR 1 minute and HIE Grade

HIE Grade Frequency APGAR 1 min Total p value

1 2 3 4 5 6
HIE I Count 1 6 6 6 0 1 20.0 0.08
percent 5.0% 30.0% 30.0% 30.0% 0.0% 5.0% 100%
HIE II Count 8 16 25 14 5 1 69
percent 11.6% 23.2% 36.2% 20.3% 7.2% 1.4% 100%
HIE III Count 4 4 0 1 0 0 9
percent 44.4% 44.4% 0.0% 11.1% 0.0% 0.0% 100%
Total Count 13 26 31 21 5 2 98

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Table 3. Cross-tabulation of HIE Grade and APGAR 5 minute

HIE Grade Frequency APGAR 5 min Total p value

2 3 4 5 6 7 8
HIE I Count 0 0 3 11 5 1 0 20 0.007
percent 0% 0% 15% 55% 25% 5% 0% 100%
HIE II Count 4 6 13 22 19 4 1 69
percent 5.8% 8.7% 18.8% 31.9% 27.5% 5.8% 1.4% 100%
HIE III Count 2 5 1 1 0 0 0 9
percent 22.2% 55.6% 11.1% 11.1% 0% 0% 0% 100%
Total Count 6 11 17 34 24 5 1 98

urine output, 21 have both deranged blood renal with 59% incidence in comparison to 41%
function test and urine output and the remaining 26 females.7
have none of these problems. Table also indicates
that there is significant association of higher level Out of 98 cases of PA with HIE, 20.4% had HIE
HIE grade with presentation of renal involvement Grade I, 70.4% had grade II HIE and 9.18% had
clinically as well as biochemically. grade III HIE. Occurrence of PA is different in
various studies.7,8,12,13 but proportion of severe
DISCUSSION forms of HIE (i,e HIE III) is less in all the studies.
In our study period of six months, we encountered Extensive newborn health awareness, trainings like
total 98 cases of PA in our institute. Like many HBB, NRP, IMNCI etc has developed skilled
other studies, our results also showed males human resources that has improved the basic
preponderance over female with PA. The ratio of resuscitation skill, that might have decreased the
males : females was 1.45:1. Male predominance is incidence of severe brain damage.
seen in most of the studies, the reason behind might A comparison of HIE grade and APGAR 1 minute
not be same but male sex is more vulnerable to shows that there is no significant association
disease like sepsis, perinatal asphyxia. Our results
between the low 1 minute APGAR score and HIE
are consistent with studies done by safaa A Medani grade. Whereas, there is significant association
et al. where they found to have more affected males between the low 5 minute APGAR score and HIE

Table 4. Cross-tabulation of HIE Grade and Mortality Table 5. Cross-tabulation of HIE Grade and Renal
case involvement

HIE Frequ Mortality Total p HIE Frequ Renal involvement P

grade ency value Grade ency value
No Yes Yes No Total
HIE I Count 19 1 20 0.009 HIE I count 3 17 20 0.00
percent 95.0% 5.0% 100.0% percent 15.0% 85.0% 100.0%
HIE II Count 55 14 69 HIE II count 60 9 69
percent 79.7% 20.3% 100.0% percent 87.0% 13.0% 100.0%
HIE Count 4 5 9 HIE count 9 0 9
III III
percent 44.4.0% 55.6.0% 100.0% percent 100.0% 0.0% 100.0%
Total Count 78 20 98 Total count 72 26 98

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 Original Article Acute Kidney Injury; Shrestha NJ et al.
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Table 6. Cross-tabulation of HIE Grade among the categories of Renal involvement

HIE Frequency Renal involvement Total p

grade value
Urea/creatinine None Decreased urine Both
derange only output only
HIE I Count 3 17 0 0 20 0.00
percent 15.0% 85.0% 0.0% 0.0% 100.0%
HIE II Count 26 9 17 17 69
percent 37.7% 13.0% 24.6% 24.6% 100.0%
HIE III Count 2 0 3 4 9
percent 22.2% 0.0% 33.3% 44.4% 100.0%
Total Count 31 26 20 21 98

grade. One minute APGAR score is not a reliable involvement of renal is high as the HIE grade
marker for brain involvement and thus continuous increases and this is statistically significant as well.
score of APGAR at 5 minutes add more value for Our result is consistent various studies.8,13 This, in
its association with brain involvement. These fact is well explained by the pathogenesis of
findings are consistent with various other similar perinatal asphyxia that in those cases with brain
studies.11,12 Studies done by Abbot R Laptook et al. involvement in perinatal asphyxia, non-vital organs
has shown that poor APGAR in 1 minute has are already being compromised and kidney is the
progressively shifted to higher values at five and 10 most common organ involved.
minutes and they have recommended importance of
10 minute APGAR score in neurological In our setting, due to high volume deliveries and
outcome.12 staff shortage, it is very difficult to calculate urine
output of each patient, so very sick cases are
Out of 98 HIE cases 79.6% survived and 20.4% catheterised for urinary output measurement while
died during course of treatment in our centre during rest of the patient’s urine output is measured by
the study period. The percentage of mortality counting the number of wet nappies. Also blood
increases with increase in the level of HIE grade. It test for renal function are delayed beyond 48 hours
shows that more than half of the cases of HIE III due to technical problems like unavailability of
had mortality i.e. 55.6%. This indicates that the visitors on time for sample transport, which causes
mortality is highly significant with HIE grade. delay in estimation of renal involvement. Thus we
Severe brain involvement in PA reflects impairment have included all suggestive measures to broaden
in diving reflex where non vital organs are already our scope to catch the renal involvement.
being compromised and in many cases even other
vital organs are being compromised.2,4 Thus In our HIE cases, renal involvement could be
mortality tends to be high in that group. Though categorised into four possible situations; it shows
mortality in studies done in developed country that, out of 98 HIE cases 31 had deranged urea/
might be different, due to advanced case creatinine only, 20 had decrease urine output, 21
management and application of therapeutic had both deranged blood test and urine output and
hypothermia,5 but mortality in developing countries the remaining 26 had none of these problems. This
remain similarly high. indicates that there is significant association of
higher level HIE grade with presentation of renal
In this study all the HIE III cases had renal involvement clinically as well as biochemically.
involvement, 87% of HIE II had some form of Similar findings were found in studies done by
renal involvement. This indicates that the Safaa A Medani et al., where their HIE case had

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 Original Article Acute Kidney Injury; Shrestha NJ et al.
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AKI up to 54%.7Among cases of studies done by sample size is need. Though the cases of this study
Ganavi Ramagopal et al. ARF was seen in 75%.8 were taken at a time where further studies
Similar results are seen in various studies as excluding sepsis in HIE cases is highly
well.14,17,20 Highest number (86%) of ARF was seen recommended.
in neonates with HIE III in a study done by
Hadzimuratovi Emnia et al., which indicated more CONCLUSIONS
renal problem in higher grades of HIE.13 Renal Renal involvement is very common in cases of
involvement is in perinatal asphyxia is obvious perinatal asphyxia, and severity of renal
after second day. Anticipation of renal involvement involvement increases as the HIE grading
in various way (i,e decreased urine output or increases.
deranged urea/ creatinine or both) should be kept in
cases of perinatal asphyxia with any degree of HIE.
In developed countries, early marker of renal
involvement is available but in developing country
like ours should be more vigilant with the urine
output and RFTs. Our study also has many
limitations as it was done in single centred and the
small sample size, further studies with larger

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