European Journal of Obstetrics & Gynecology and Reproductive Biology 225 (2018) 205–209

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European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Full length article

Pregnancy-related acute kidney injury requiring dialysis as an indicator

of severe adverse maternal morbidity at a tertiary center in Southwest
Nigeria
Ibraheem O. Awowolea,* , Oluseyi S. Omitindeb , Fatiu A. Arogundadec ,
Sekinah B. Bola-Oyebamijid , Olumide A. Adeniyib
a
Department of Obstetrics, Gynaecology and Perinatology, Obafemi Awolowo University, Ife, Osun State, Nigeria
b
Department of Obstetrics and Gynaecology, Obafemi Awolowo University Teaching Hospitals Complex, Ife, Osun State, Nigeria
c
Nephrology Unit, Department of Medicine, Obafemi Awolowo University, Ife, Osun State, Nigeria
d
Department of Obstetrics and Gynaecology, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Osun State, Nigeria

A R T I C L E I N F O A B S T R A C T

Article history: Objective: Despite being a Critical Intervention in the WHO Near-miss concept, the indications and clinical
Received 27 November 2017 outcomes of patients with Pregnancy-Related Acute Kidney Injury (PRAKI) requiring dialysis at the Obafemi
Received in revised form 25 March 2018 Awolowo University Teaching Hospitals Complex, Nigeria remain unknown. This retrospective review was
Accepted 30 April 2018
conducted to facilitate counselling, prognostication and introduction of preventative measures by providing
contemporary data on the aetiology and clinical outcomes of women with PRAKI.
Keywords: Study design: A retrospective review. The indications for dialysis and feto-maternal outcomes of women
Dialysis
with PRAKI requiring dialysis between January 2007 and December 2016 were reviewed. Analysis was
Pregnancy-related acute kidney injury
Near-miss
performed with IBM SPSS 21.0.
Nigeria Results: There were 43 patients with PRAKI that required dialysis and 11,242 live births, with Maternal Near
Maternal mortality Miss Ratio (MNMR) of 3.8/1000 live births. Preeclampsia/ecclampsia (40%), Sepsis (37.5%) and
Haemorrhage (20%) were the leading aetiologies of kidney injury, while oligo-anuria (100%) was the
commonest clinical presentation. Majority (78%) of them had four dialysis sessions before recovery of
renal function. The mean (SD) gestational age and birth weight at delivery were 36 (3.1) weeks and 2.9
(0.6)kg, while the Maternal Mortality Index and Perinatal mortality rates were 18% and 34% respectively.
Delayed referral, and lower number of dialysis sessions were the significant predictors of mortality, while
four women discontinued care due to cost.
Conclusion: The high rate of Pregnancy-related acute kidney injury requiring dialysis, with its attendant
morbidity and mortality are largely preventable. The prognosis is however good with standardised care.
Functional emergency obstetric services, and a review of the Nigerian healthcare financing system are
advocated.
© 2018 Elsevier B.V. All rights reserved.

Introduction termination of pregnancy” [1]. It is estimated that approximately

Severe Adverse Maternal Morbidity (SAMM) or Near-miss is
defined as “a woman who nearly died but survived a complication
that occurred during pregnancy, childbirth or within 42 days of
* Corresponding author at: Obafemi Awolowo University, College of Health
Sciences, Department of Obstetrics and Gynaecology, Ile-Ife, Osun State, 220005,
Nigeria. Tel.: +234 8033767719.
E-mail addresses: ibraheem.awowole@nhs.net (I.O. Awowole),
getaquasteve@yahoo.com (O.S. Omitinde), fatiu3@yahoo.com (F.A. Arogundade),
sek_aiy@yahoo.com (S.B. Bola-Oyebamiji), adeniyidotun@gmail.com
(O.A. Adeniyi).
20–30 women will suffer long and short term morbidity for every
reported case of maternal mortality. The maternal near miss
concept therefore provides much more robust data than those
obtained from maternal mortality reviews. By evaluating cases of
severe adverse maternal morbidity, a lot can be learnt about the
processes in place for the care of pregnant women [2,3]. Dialysis for
renal dysfunction (acute or chronic) in pregnancy, labour or up to
42 days after the termination of pregnancy is classified as a Critical
intervention in the Near-miss concept. Currently, obstetric practice
is increasingly being challenged by women with acute kidney
injury, varying severity of pre-existing chronic kidney diseases,
and even renal transplant patients with pregnancy [4].

https://doi.org/10.1016/j.ejogrb.2018.04.041
0301-2115/© 2018 Elsevier B.V. All rights reserved.

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206 I.O. Awowole et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 225 (2018) 205–209
Pregnancy-Related Acute Kidney Injury (PRAKI) is an infrequent
but challenging clinical problem, and kidney injuries that are
severe enough to require dialysis in pregnancy are even more
uncommon [5]. As the aetiology of kidney injury in the obstetric
population may be pregnancy-specific or due to any of the
disorders that may cause AKI in the general population, effective
management of kidney disease in pregnancy or puerperium
demands a clear understanding of the aetiology and natural
history of the kidney injury, and implementation of diagnosis-
specific treatment, together with general supportive care and
dialysis where appropriate. Often, these women demand informa-
tion about their clinical conditions, possible outcomes and
prognoses. Satisfactory response to these are however impossible
without accurate and contemporary clinical data. Despite being
one of the only two dialysis centres that are available in Osun State,
Southwest Nigeria, the indications, pattern of presentation and the
clinical outcomes of obstetric patients that had been managed at
the dialysis unit of the OAUTHC, Ile-Ife remains to be documented.
This review was therefore conducted to generate information that
will be useful for patient’s counselling and clinical prognostication.
Furthermore, where gaps are identified in the care of the patients,
necessary suggestions will be made and communicated to the
appropriate authority.
Materials and methods
The records identification numbers of all patients with
diagnoses of renal failure at the hospital between January 2007
and December 2016 were retrieved using the ICD-10 codes N17-
N19. These were reconciled with the records at the Maternity and
the Haemodialysis units to identify women that underwent
dialysis in pregnancy, labour and up to 42 days after the
termination of pregnancy for acute kidney injuries. Eligibility
was irrespective of the gestational age at which the dialysis was
done; consequently, women with kidney injuries from early
pregnancy complications such as septic abortions and ectopic
pregnancies were included. Data relating to the socio-demograph-
ic characteristics, pattern of presentation, indication for dialysis
and feto-maternal outcomes were obtained using a purpose-
designed dataform. Analysis was performed with the IBM-SPSS
21.0. Frequency tables and charts were utilised for data presenta-
tion. As this review was retrospective and completely anonymized,
ethical approval was not sought.
Definition of terms
Acute Kidney Injury (AKI) was defined as Failure in RIFLE
staging or stage III of AKIN or KDIGO staging, which is the abrupt
loss of kidney function, resulting in the retention of urea and other
nitrogenous waste products and in the dysregulation of extracel-
lular volume and electrolytes that is severe enough to warrant
dialysis [6]. Puerperal sepsis was defined as an infection of the
genital tract occurring at any time between the onset of the rupture
of membranes or labour and the 42nd day postpartum in which
two or more of the following are present- pelvic pain, fever,
abnormal vaginal discharge, abnormal odour of discharge or delay
in the rate of reduction of size of the uterus [7]. Preeclampsia was
defined as elevated blood pressure of at least 140/90 mmHg on two
different occasions, first diagnosed after the 20th week of
pregnancy with significant proteinuria [8]. Primary postpartum
haemorrhage was defined as bleeding from the genital tract in
excess of 500 mls after vaginal delivery or 1000 mls after caesarean
section within the first 24 h of delivery [9]. Preterm delivery was
defined as delivery before a gestational age 37weeks + 0days.
Maternal Near-Miss Ratio (MNMR) refers to the number of
maternal near-miss cases per 1000 live births, and Maternal
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Mortality Index (MMI) was derived from the number of maternal
deaths divided by the number of women who had dialysis due to
PRAKI, expressed as a percentage.
Results
There were 43 patients with PRAKI severe enough to warrant
dialysis, and 11,242 livebirths, with a Maternal Near-Miss Ratio of
3.82/1000 livebirths for PRAKI requiring dialysis. Three patients
were excluded due to incomplete records; further analysis was
therefore based on 40 patients.
Their mean age was 29.19(5.69)years, with a range of 18–40
years Table 1, while their parity ranged between 0 and 6, with a
median of 2. Eleven women (27.5%) were admitted in the first
trimester (ten with septic induced abortions and one ectopic
gestation complicated by severe haemorrhage). Nine women
(22.5%) were admitted in the third trimester, and 20 women (50%)
were admitted postpartum.
Preeclampsia/ecclampsia (n = 16; 40%), septic abortion (n = 10;
25%), obstetric haemorrhage (n = 7; 17.5%) and puerperal sepsis
(n = 5; 12.5%) were the leading aetiologies of the AKI (Table 2).
Oliguria was the presenting complaint in all the women. The other
clinical features were uraemia (n = 26; 65%) and pulmonary
oedema (n = 6: 15%). Biochemical derangements were also preva-
lent; all the women had elevated serum urea and creatinine
concentrations, with mean urea concentration of 24.36(8.37)
mmol/l and mean creatinine concentration of 606.28(203.15)m
mol/l. Only a third of them had elevated potassium leve (Table 3).
Haemodialysis was the only mode of dialysis that was adminis-
tered to all the patients. The number of dialysis sessions ranged
between two and thirteen, with a median of three sessions
(Table 4). Thirty-six women (90%) had blood transfusion as
adjunctive treatment for the correction of anaemia, while the
remaining patients had intravenous iron infusion with erythropoi-
etin therapy. Hypotension was the only complication of haemo-
dialysis, recorded in four (10%) of the women.
Seven of the twenty-nine women that carried their pregnan-
cies beyond the age of viability (taken as 28 weeks) had preterm
delivery, and 16 women had caesarean sections, giving preterm
delivery and caesarean section rates of 24.1% and 55.2%
respectively. The mean gestational age at delivery was 36.50
(3.09)weeks, with an average birth weight of 2.87(0.55)kg. The
duration of hospital stay among the subjects ranged from one to
133 days, with a mean of 33 days. Seven maternal deaths (four
among the patients with eclampsia and three from the postpar-
tum haemorrhage cohort) and ten perinatal deaths were
recorded, with maternal and perinatal case fatality rates of
17.5% and 34.4% respectively. There were two concurrent feto-
maternal deaths.
Following therapy, 29 women (72.5%) achieved full recovery of
renal functions within three months, and were subsequently
Table 1
Demographic and biochemical characteristics of women with pregnancy-related
dialysis based on survival status at OAUTHC, Ile-Ife.
Parameters Mean  SD
Survived (n = 33) Died (n = 7)
Age (years) 29  6.1 27  2.4
Latency interval (days)a 3.2  0.72 6.0  1.1
Urea (mmol/L) 25  8.7 28  10
Creatinine (umol/L) 595  25 696  22
Potassium (mmol/L) 4.6  1.2 4.6  1.2
Number of dialysis 4.0  1.2 1.0  0.3
Duration of hospital stay (days) 40  8.1 5.3  1.7
a
Mean interval (in days) between onset of oliguria and referral to the dialysis
center.
 I.O. Awowole et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 225 (2018) 205–209 207

Table 2 AKI is a late complication in the sequence of events in hypertensive

Aetiology of Renal Impairment among Patients with Pregnancy-related Dialysis.
disorders of pregnancy, early diagnosis and conscientious man-
Causes Frequency Percentage agement of hypertension in pregnancy at its onset will no doubt
Pre-eclampsia/eclampsia 16 40 contribute significantly to the reduction of acute kidney injuries in
Septic Induced Abortion 10 25 pregnancy. Unfortunately, a significant proportion of Nigerian
Obstetric haemorrhage 7 18 women either commenced antenatal care late, or did not benefit
Puerperal sepsis 5 12
from such care at all [15]. This category of women constitutes the
Drug-induceda 2 5
Total 40 100
majority in this review, as well as another report from Northern
Nigeria [16]. The delayed referral of these women until their
a
Second generation cephalosporin administered as pre-operative prophylaxis for clinical status had become moribund was further affirmed by the
elective caesarean section.
observation that four (57.1%) of the seven mortalities in this review
were recorded in this cohort. Improvement in the nationwide
coverage of standardised antenatal care services, Skilled Birth
Table 3
Pre-dialysis Biochemical Profile of Women with Pregnancy-related Dialysis at Ile- Attendants at all deliveries, and a well-coordinated obstetric
Ife. referral system are therefore advocated.
Consistent with earlier reports from Nigeria [16], India [17],
Electrolyte Concentration Frequency %
and Morroco [14], sepsis also ranked second as a cause of PRAKI
Urea (mmol/L)
requiring dialysis in this study. While this is a composite group,
<10 6 15
10–19 12 30 comprising septic induced abortions and puerperal sepsis, the
20–29 13 33 former clearly predominates (67% vs 33%). The high proportion
>30 9 22 of kidney injuries due to septic induced abortion for unwanted
pregnancies is therefore of genuine concern. Indeed, this is a
Creatinine (umol/L)
<500 6 17
socio-medical problem that may be significantly reduced by
500–599 8 23 public enlightenment, female education, contraceptive aware-
600–699 5 15 ness and other preventive measures for unwanted pregnancies.
700–799 3 9 Cost barriers should be eliminated, so that even the very poor
800–899 4 12
can have unlimited access to contraceptives. In addition, skilled
900 8 23
birth attendant, strict asepsis at delivery, early identification of
Potassium (mmol/L) women at risk, and the judicious use of antibiotic therapy are
3.0–4.0 11 28 necessary to reduce the burden of renal dysfunction due to
4.1–5.0 15 37 puerperal sepsis.
>5.0 14 35
The WHO Emergency Obstetric Care guidelines dictate that all
health facilities, irrespective of whether they are basic or
comprehensive, must be able to administer parenteral oxytocics
Table 4
for the prevention and management of postpartum haemorrhage
Number of Dialysis Sessions among Women with Pregnancy-related Dialysis at [18]. The judicious implementation of this recommendation will
OAUTHC, Ile-Ife. greatly reduce the prevalence and severity of obstetric haemor-
rhage, which not only caused 14.7% of the acute kidney injuries, but
Dialysis sessions Frequency Percentage
was also the diagnosis in three (42.9%) of the seven mortalities in
1–2 14 35
this study.
3–4 17 42
5–6 3 8 In normal pregnancies, the serum concentration of creatinine
>6 6 15 falls due to increased glomerular filtration rate (hyperfiltration),
Total 40 100 and as such, lower reference limits have been advocated for
pregnant women. Progressive elevation of the serum urea and
creatinine levels despite pregnancy therefore calls for a critical
evaluation of renal function. Expectedly, all the women that were
discharged from the Nephrology clinic after six months of follow- dialysed in this review had abnormally elevated serum concen-
up, while the remaining four patients (10%) self-discharged trations of urea and creatinine. On the contrary, serum potassium
themselves from medical services due to financial constraints. level was not a reliable indicator of renal performance, as only a
third of the subjects had hyperkalaemia.
Comment With regards to their obstetric performance, the preterm
delivery rate of 24% in this series is higher than the reported rate
The study describes the indications for dialysis and the for the general obstetric population. Expectedly, the caesarean
obstetric outcomes of women who had pregnancy-related section (CS) rate of 56% among the 25 women that carried the
dialysis at the Obafemi Awolowo University Teaching Hospitals pregnancy beyond the age of viability in this study is higher than
Complex, Ile-Ife, Osun State, Nigeria over the ten year period hospital baseline CS rate of about 37%. Although, the perinatal case
between January 2007 and December 2016. The pregnancy- fatality rate of 34.4% in this study is better than the 87.5% fetal loss
related dialysis rate of 3.8 per 1000 deliveries in this study is rate reported from Zaria, Northwest Nigeria [16], it is almost triple
similar to the 1.78/1000 and 2/1000 deliveries reported from the 13.6% reported from a Canadian series where the women had
other developing countries such as India and Morocco respec- intense feto-maternal surveillance [19]. Efforts should therefore be
tively [10,11]. The prevalence was however much higher than the intensified to improve the perinatal outlook of babies delivered to
average dialysis rate from developed countries, reported to be as these women.
low as 1/20,000 live births [12]. All the women in this review had haemodialysis performed on
PRAKI due to preeclampsia/eclampsia comprised the most them, although some other studies also reported the use of
prevalent aetiology in this review, consistent with findings from continuous ambulatory peritoneal dialysis with good outcomes
earlier studies conducted in Morocco, Brazil and India [11,13,14]. As [20–22]. Twenty-two (75.9%) of the 29 women that survived

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208 I.O. Awowole et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 225 (2018) 205–209
required four sessions or less of haemodialysis in this series before
attaining sufficient recovery of renal functions. Excluding the
mortalities and the women that discontinued their care, all the
remaining 29 patients achieved complete recovery of their renal
function within three months of delivery, and none of them
progressed to chronic renal failure. This information may form the
platform upon which future counselling and prognostication of
patients with PRAKI requiring haemodialysis will be based.
The Maternal Mortality Index of 17.5% in this study is
comparable to the 18–25% reported among women undergoing
pregnancy-related dialysis in other developing countries [17], in
contrast to the 4.3% that was reported from Canada [5]. Severe
sepsis and massive obstetric haemorrhage had been reported as
the two leading clinical conditions associated with maternal
mortality among women with pregnancy-related renal dysfunc-
tion [10,23]. Obstetric haemorrhage (42.9%) and ecclampsia (57.1%)
were however the causes of maternal demise in this study, while
none was recorded among the women with sepsis. A similar
observation had also been reported by Okunola et al. from Nigeria,
where obstetric haemorrhage (30%) and ecclampsia (70%) were
associated with maternal mortality, while there was no mortality
among the patients with kidney injuries from sepsis [24].
Late recognition of AKI, culminating in delayed referral for
dialysis as displayed on Table 1 contributed to the fatality rate in
this study. Compared with survivors, the seven women that died
had significantly longer latency interval between onset of oliguria
and referral for dialysis (p = 0.03), less number of dialysis sessions
(p = 0.04) and overall, a significant shorter duration of hospital stay
before their demise (p = 0.01). These observations underpin their
poor clinical status at admission, leaving little or no time for
effective interventions. Three patients discharged themselves from
further care due to financial constraints. Similarly, four of the eight
women from Northwest Nigeria who had pregnancy-related
haemodialysis [16] discontinued their care due to the same
reason; while the clinical outcomes of these women are unknown,
the imagined possibilities remain bothersome. These findings
strongly highlight the adverse impact of the Nigerian healthcare
financing system, which currently relies heavily on “out of pocket”
payment on the management and outcome of these women. To
achieve the Sustainable Development Goal target of reducing
maternal mortality ratio globally to less than 70/100,000 live
births, developing countries like Nigeria must address these
remote contributors to maternal mortality.
Limitation
Only women with PRAKI that was severe enough to warrant
dialysis were included in this review. By implication, the results
from this study may not be applicable to other women with PRAKI
that were managed without dialysis (RIFFLE stages 1 and 2). In
addition, the number of cases available for this review may not be
sufficient for conclusive inferences to be made. Nevertheless, this
study has provided some insight into the aetiology, outcomes and
challenges encountered in the management of women with PRAKI
requiring dialysis at OAUTHC Ile-Ife; an information that hitherto
wasn’t available.
Conclusion
Severe Adverse Maternal Morbidity due to PRAKI requiring
dialysis at OAUTHC, Ile-Ife occurred more frequently compared
with developed countries. Although the prognosis is good if
promptly recognized and managed appropriately, delayed recog-
nition of obstetric complications, late referrals and the high cost of
treatment contributed significantly to the disturbing Maternal
Mortality Index and Perinatal case fatality rates associated with the
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condition. Training-retraining of health care workers in Emergency
Obstetric Care, early recognition of complications and effective
coordination of referrals are necessary. Furthermore, prevention of
unwanted pregnancies and a review of the Nigerian healthcare
financing system are advocated to improve the outlook of the
patients.
Competing interests
The authors declare no competing interests.
Funding
No funding was received for this study.
Authors contribution
AIO conceived the study. The protocol and data collection was
done by AIO, OOS and FAA. Data analysis and preparation of
manuscript was done by AIO, OOS, FAA and AOO. All the authors
critically read and approved the manuscript in its present form.
Acknowledgement
The kind assistance of the nephrology unit nurses to the
preparation of this manuscript is hereby acknowledged.
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