Abstract Introduction Methods Data Analysis Plan Results Discussion Conclusion Declarations References

An Evaluation of Risk Factors Associated with Pregnancy Related Acute Kidney Injury in Women Admitted to the High Dependency Care Unit at Women and Newborn Hospital, Lusaka-Zambia

Karen Mutemwa Imasiku
University Teaching Hospitals, Women and Newborn Hospital, Lusaka, Zambia

Lackson Kasonka
University Teaching Hospitals, Women and Newborn Hospital, Lusaka, Zambia

DOI: https://doi.org/10.55320/mjz.49.2.977

Keywords:Pregnancy-related acute kidney injury, creatinine, eclampsia, preeclampsia, and postpartum haemorrhage.

ABSTRACT

Objective:To evaluate factors associated with Pregnancy-related Kidney Injury (PRAKI) in women admitted to high dependent care unit at Women and Newborn Hospital in Lusaka, Zambia

Methodology: This was an unmatched case-control study conducted in the high-dependent care unit at Women and Newborn Hospital in Lusaka. Study participants were recruited consecutively by convenient sampling. Participants’ medical records were reviewed to capture serum creatinine levels; while a structured questionnaire was administered to eligible and consented study participants to capture data on sociodemographic, obstetric and medical factors. Serum creatinine levels above 84µmol/l were used as criteria for classifying PRAKI. Excel was used for data cleaning and Stata v13 used for analysis. Descriptive statistics were done for all variables followed by univariate and multivariable logistic regression to determine association. 95% CI was used and p value of < 0.05 was considered significant.

Results: The study comprised of 185 study participants, split into 85 women with PRAKI (cases) and 100 women without PRAKI (controls). The median age was 29 years with 11years interquartile range. 75.3% (139) of the study participants were in marriage relationships. Pre-existing hypertension was the most prevalent medical condition in both the cases (51.8%) and the controls (38%). Sickle cell disease was much less common at 1.2% in cases and 8% in controls. Among the obstetric conditions, preeclampsia was the most prevalent condition at 77.6% and 60% in cases and controls respectively. Eclampsia was found in 38.8% of cases and 11% of controls. Sepsis was least common at 4.7% of cases. This study found that obstetric factors such as eclampsia (AOR = 5.12, 95% CI [2.14 – 12.23]; p≤0.0001), preeclampsia (AOR = 2.46, 95% CI [1.12 – 5.39]; p = 0.025), and postpartum haemorrhage were associated with the development of PRAKI. Medical conditions were not associated with PRAKI.

Conclusion: Thus the development of PRAKI was mainly associated obstetric factors such as eclampsia, preeclampsia, and post-partum haemorrhage.

INTRODUCTION

Pregnancy-related acute kidney injury (PRAKI) is an acute renal dysfunction that occurs in pregnancy or puerperium. It is characterised by abrupt decrease in kidney function leading to accumulation of nitrogenous waste products and other uremic toxins.[1] [2] It occurs between 6% and 55% of pregnant women and overall, is one of the most common causes of acute kidney dysfunction, contributing 20% – 40% of all cases.[3] ( PRAKI is associated with development of chronic kidney disease and end-stage renal disease, hypertension, cardiovascular disease, maternal mortality and poor foetal outcomes including still births and perinatal mortality.[4] [5]

Globally, there has been a dramatic decrease in the incidence of PRAKI over the past 50 years. This reduction, however, has not been uniform worldwide.[6] In developed nations, the incidence is 1%-2.8% while in developing countries PRAKI is still frequent and its incidence varies considerably from country to country.[7] [8] A study in Morocco found PRAKI rates of 66 per 10,000 deliveries[9] while in Malawi it was 8.1%.[10] Although the incidence of PRAKI has significantly decreased in the developed world, it remains a serious public health problem in developing countries where there is limited access to prenatal care and to abortion services.[5] [11] A number of aetiological factors are involved in the pathobiology of PRAKI, including obstetric factors and medical factors. Some of the obstetric and medical factors include septic abortion, puerperal sepsis, preeclampsia, postpartum haemorrhage, gestational hypertension, heart failure, hyperemesis gravidarum, and renal disease.[12] [10] In high income countries, the causes of PRAKI are slightly different and include pregnancy-specific diseases like preeclampsia/eclampsia (PE/E), haemolysis/elevated liver enzymes/low platelet count (HELLP) syndrome, thrombotic micro-angiopathy of pregnancy (P-TMA), haemorrhage by abruption placentae, and acute fatty liver of pregnancy (AFLP).[13]

The maternal and foetal morbidity and mortality as a result of PRAKI is largely due to potentially preventable complications and complete renal recovery is achievable with appropriate and timely management.[14] Knowledge of the risk factors underlying PRAKI in developing countries is limited to enable appropriate triage and targeting of scarce resources.[15] PRAKI is more common in under-resourced countries, including Zambia, where it is less well studied. The difference in the access to health care among the rural and urban populations in Zambia could be recognised as an important factor associated with poor maternity outcomes among the impoverished rural women. This study was aimed at evaluating the socio-demographic, medical, obstetric and gynaecological risk factors associated with the development of PRAKI in women with and without the disease. The study was conducted over a period of six months at Women and Newborn Hospital (WNH) in Lusaka city of Zambia.

METHODS

This was an unmatched case-control study conducted in the high-dependency care unit (HDU) in the WNH for six months’ duration between 1st February and 31st July 2020. WNH is a tertiary level hospital and a referral centre for maternity and gynaecological complications. It has a high dependency unit that is essentially the hospital’s intensive care with six beds for critical nursing care, two of which are equipped with ventilation support equipment. Adjacent to the intensive care is the step-down care unit with a further six beds for high dependency nursing care. Acute or chronic kidney dysfunction at any stage of pregnancy forms a hospital criterion for admission to this ward. Study participants were recruited consecutively by convenience sampling. A case was defined as a pregnant woman at any gestational age or a woman in puerperium with serum creatinine equal to or above 84µmol/l; while those with creatinine levels less than 84µmol/l were categorized as controls. Participants’ medical records were reviewed to capture serum creatinine levels while a structured questionnaire was administered to eligible and consented study participants to capture data on sociodemographic, obstetric, and medical factors. Serum creatinine levels above 84µmol/l were used as criteria for classifying PRAKI. The questionnaire was administered in a face-to-face interview by four specifically trained qualified midwives who worked in the HDU ward on different shifts to ensure 24 hours coverage. Where necessary, verification and additional information was obtained from patient medical files and collateral history from relatives. Participants for recruitment were selected based on the attending obstetrician’s clinical diagnosis of acute kidney injury.

DATA ANALYSIS PLAN

The raw data were cleaned and coded in Excel and was then exported to Stata/SE version 13 (STATA Corp. College Station, Texas, USA) for analysis. Binary and categorical data were summarized as frequencies and expressed in percentages. Chi-square test was used for categorical variables where the frequencies were above 5, below that Fisher’s exact test was used. For continuous variables such as age, a normality test using Shapiro-Wilk test was done to determine whether the age was normally distributed or not. Since the age was not normally distributed, Mann–Whitney U test was used, and median and interquartile range were reported. Univariate conditional logistic regression analysis was conducted to determine a crude (i.e., unadjusted) association between the outcome (PRAKI) and one independent variable. To identify factors associated with development of PRAKI after adjusting for confounders, multivariable conditional logistic regression was conducted with probability of variables being included in the final model set at 20%. Odds ratio was computed to estimate the strength of association. Confidence interval of 95% was used and p value of less than 0.05 was considered significant.

RESULTS

Descriptive statistics

Altogether 185 women were enrolled in this unmatched case-control study with 85 cases and 100 controls. The median age of the women was 29 years with interquartile range of 11 years and more women fell in the age range of 30 to 34 years (25.1%). About two thirds lived in the high-density areas of Lusaka and majority of the study participants (75.1%) were married. Pre-existing hypertension was the most prevalent medical condition in all the participants accounting for 44.3%. Sickle cell disease was much less common at 4.9%. Among the obstetric conditions, preeclampsia was the most common at 68.1% followed by eclampsia (23.8%). Sepsis was observed in 4 (2.2%) of all the women (Table 1).

Proportions of Socio-demographic, Medical and Obstetric factors between cases and controls

PRAKI was more commonly diagnosed in women aged 25 – 34 years (27.1%), with median age of 29 years. Majority of the women were married in both cases and controls, (cases = 75%, controls = 75.3%) compared to those that were single (cases = 25%, controls = 24.7%), though this difference was not statistically significant (p = 0.963). Furthermore, majority of the women came from high residential areas of Lusaka (cases = 62.4%, controls = 60%). The most prevalent medical condition was pre-existing hypertension in both, 51.8% in the cases and 38% in the controls, though the difference was not statistically significant (p = 0.060). Although diabetes mellitus (DM) can frequently complicate kidney function, there was no apparent difference in the presence of DM in the cases and the controls (5.9% vs 6%). There was higher frequency of both pre-eclampsia (77.6%) and eclampsia (38.8%) in the women with PRAKI compared to 60% and 11% respectively in the controls. These differences were highly statistically significant (p = 0.010 vs <0.0001). Similarly, there was higher frequency of hyper-emesis gravidarum (18.8%) in women with PRAKI compared to 13% in the control group, a difference which nevertheless was not statistically significant (p = 0.278). Obstetric haemorrhage (both pre- and postpartum) was observed more frequently in women with acute renal dysfunction (34.1%) compared to 13% in those without. These differences carried high statistical significance (Table 2). Sepsis due to puerperal infection and/or unsafe abortion was only present in women with PRAKI (4.7%).

Table 1: Descriptive characteristics of the study participants (n = 185) with and without PRAKI

Table 2: Proportions of socio-demographic, medical and obstetric factors between cases and controls

Univariate logistic regression analysis of socio-demographic, medical and obstetric factors in relation to development of PRAKI

Univariate conditional logistic regression analysis showed that age was not associated with risk of developing PRAKI (p>0.05). The odds for PRAKI in single (unmarried) women were 1.02 (COR = 1.02, 95% CI [0.52-1.98]; p = 0.983) compared to married women although not statistically significant.

In this analysis, the women with DM appeared to be 2% less likely to develop the AKI compared to those without diabetes (COR = 0.98, 95% CI [0.29 – 3.33]; p = 0.973). This finding, however, was not statistically significant. Similarly, sickle cell disease appeared protective from PRAKI in this analysis (COR = 0.14, 95% CI [0.02 - 1.12]; p = 0.063). This fallacy owes to the small numbers of sickle cell patients analysed in both the groups. As anticipated, hypertensive disorders of pregnancy and obstetric haemorrhage had higher odds for developing PRAKI showing high statistical significance (Table 3).

Multivariable conditional logistic regression analysis assessing variables for development of PRAKI

After univariate analyses for socio-demographic, medical and obstetric characteristics, variables with p-values less than or equal to 0.2 (20%) were selected for multiple conditional logistic analysis. In this analysis, only significant results were reported while adjusting for all other variables in the model. Women who had eclampsia (AOR = 5.12, 95% CI [2.14 – 12.23]; p<0.0001), preeclampsia (AOR = 2.46, 95% CI [1.12- 5.39]; p = 0.025) and post-partum haemorrhage (AOR = 4.29, 95% CI [1.54 – 11.89]; p = 0.005) were more likely to have PRAKI compared to those without these conditions.

Table 3: Univariate conditional logistical regression of socio-demographic, medical and obstetric factors in relation to development of PRAKI

Table 4: Multivariable conditional logistic analysis for association between PRAKI and predictor

DISCUSSION

This study found that eclampsia had the higher odds of development of PRAKI followed by postpartum haemorrhage (PPH) and then preeclampsia (Table 4). This was in contrast to a study done in Morocco in 2013 where preeclampsia was the main risk factor for PRAKI, followed by eclampsia.[9] Similarly, another Moroccan study two years later found that preeclampsia was the most common cause, then septic events and pregnancy haemorrhages.[16] On the contrary, a study done in India in 2008, found that puerperal sepsis was the major risk factor associated with development of PRAKI, followed by obstetric haemorrhage.[17] Eclampsia was the commonest associated risk factor for PRAKI in this study possibly because of the high prevalence of preeclampsia in African women occurring in 10% of pregnancies, compared to a global average of 2%.[19] Risk factors for preeclampsia include black race, maternal anaemia and infections, multi-parity, and low socioeconomic status that are all highly prevalent in African women.[20] [21] Preeclampsia is a multisystem disorder with an unclear pathogenesis but is a condition characterized by new-onset hypertension and proteinuria after 20 weeks’ gestation.22 In preeclampsia, there are haemodynamic derangements that result in decrease in renal plasma flow, glomerular filtration rate and vasoconstriction of renal vessels predisposing the kidneys to ischaemic injury.

In Africa the major risk factors associated with PRAKI are sepsis, hyperemesis gravidarum and hypertensive disorders of pregnancy (these include eclampsia and preeclampsia).[14] [18] [10] Sepsis in this study included both post abortion and puerperal sepsis. However, all the participants with sepsis in this study belonged to the cases and non in the controls, therefore this variable was dropped in logistic regression analysis.

In this study, PPH was associated with increased risk of developing PRAKI by four-fold. However, the results were not statistically significant for APH. In a study done in Canada, the results showed that PPH was the commonest risk factor for PRAKI.[24] PPH can lead to hypovolaemia due to hypoperfusion of the parts of kidneys and subsequent reduction in glomerular filtration rate. If the state of hypovolaemia is sustained, ischaemic injury to parts or all of kidney ultimately occurs.[23]

Pre-existing hypertension and diabetes mellitus though are linked to the pathophysiology of PRAKI, in this study association was not significant (p>0.05). However, the proportion of hypertension was more among the cases (51.8%) than the controls (38%).

In this study, Human Immunodeficiency Virus (HIV) was more common in the cases than in controls, although not statistically significant. Similarly (as HIV) Malaria was found to be more common among participants with PRAKI than controls in the current study. The likelihood of developing PRAKI in a participant who had malaria was 34% compared to participants that did not have malaria. In contrast, a study in Pakistan found malaria in only 2.3 % of patients with PRAKI.[25] According to WHO, the majority of cases of malaria happen in sub-Saharan Africa and pregnant women are at considerably higher risk of contracting malaria and developing severe disease.[26] Women are increasingly susceptible to malaria during pregnancy because Plasmodium falciparum, the most common parasite responsible for malaria avoids spleen clearance by binding to the placenta.[20]

Sickle cell disease in this study was surprisingly more common in the controls. In contrast, in a survey in United States found that PRAKI was more common among women with SCD 10 (0.7%) (p <0.0001) compared to women without SCD.[27] This could be due to improvements in medical care and management of SCD patients that has resulted in reduced morbidity and mortality associated with the condition. The other reason could be that SCD being a chronic non-communicable disease increases the likelihood and frequency of seeking qualified care resulting in less consequences such as those posed by PRAKI.28 Repeated vaso-occlusive crises in multiple organs can lead to a number of complications including renal dysfunction, pulmonary hypertension and stroke among others.

CONCLUSION

This study found that the development of PRAKI was mainly associated with obstetric factors such as eclampsia, preeclampsia, and post-partum haemorrhage.

DECLARATIONS

ETHICAL APPROVAL
For the conduct of this research, approval was obtained from the University of Zambia Biomedical Research Ethics Committee (UNZABREC, REF. No. 312-2019), and National Health Research Authority (NHRA). Signed consent forms from all eligible participants were obtained prior to enrolment. Participants’ information was kept confidential throughout the study, and numbers were used instead of names.

CONFLICT OF INTEREST
We affirm that we did not have any conflict of interest during the execution of this study.

FUNDING STATEMENT
This study was sponsored by DIPLOMATIC project

ACKNOWLEDGEMENT
This study was conducted in Lusaka city of Zambia at the Women and Newborn Hospital, housed in the largest referral tertiary Hospital. We herewith acknowledge the contributions of the Women and Newborn Hospital staff, our mentors and teachers, and the DIPLOMATIC project team for their excellent support. We are also grateful to the women that were admitted to HDU and that took part in this study.

REFERENCES

  1. Li X, Wu X, Zhang M, Xu L, Li G, Wen Y, Wang W,. Pregnancy-related acute kidney injury at high altitude: a retrospective observational study in a single center. BMC Nephrol [Internet]. 2021 Dec 1 [cited 2022 Mar 5];22(1):1–10. Available from: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02418-7
  2. Makris K, Spanou L. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes. Clin Biochem Rev [Internet]. 2016 May [cited 2019 Feb 7];37(2):85–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28303073
  3. Siribamrungwong M, Chinudomwong P. Relation between acute kidney injury and pregnancy-related factors. J Acute Dis. 2016;5(1):22–8.
  4. Siew ED, Davenport A. The growth of acute kidney injury: A rising tide or just closer attention to detail? [Internet]. Vol. 87, Kidney International. Elsevier Masson SAS; 2015. p. 46–61. Available from: http://dx.doi.org/10.1038/ki.2014.293
  5. Bokhari SRA, Inayat F, Jabeen M, Sardar Z, Saeed S, Malik AM, et al. Characteristics and Outcome of Obstetric Acute Kidney Injury in Pakistan: A Single-center Prospective Observational Study. Cureus. 2018;10(9).
  6. Rao S, Jim B. Acute Kidney Injury in Pregnancy: The Changing Landscape for the 21st Century. Vol. 3, Kidney International Reports. 2018. p. 247–57.
  7. Abdollahpour A, Doustmohammadi H, Sadeghi L, Hosseinzadeh Zoroufchi B. Acute renal failure during the pregnancy: a review on pathophysiology, risk factors and management. J Ren Inj Prev [Internet]. 2018;7(4):314–20. Available from: http://www.journalrip.com/Abstract/jrip-531
  8. Haroon F, Dhrolia MF, Qureshi R, Imtiaz S, Ahmed A. Frequency of pregnancy-related complications causing acute kidney injury in pregnant patients at a tertiary care hospital. Saudi J Kidney Dis Transpl. 2019;30(1):194–201.
  9. Arrayhani M, El Youbi R, Sqalli T. Pregnancy-Related Acute Kidney Injury: Experience of the Nephrology Unit at the University Hospital of Fez, Morocco. ISRN Nephrol. 2013;2013:1–5.
  10. Cooke WR, Hemmilä UK, Craik AL, Mandula CJ, Mvula P, Msusa A, et al. Incidence, aetiology and outcomes of obstetric-related acute kidney injury in Malawi: A prospective observational study. BMC Nephrol. 2018;19(1):1–8.
  11. Aghwana R, Onohwakpor E, Okoye O. Sun-167 Pregnancy Related Acute Kidney Injury In Delta State University Teaching Hospital, Nigeria. Kidney Int Reports [Internet]. 2019;4(7):S228. Available from: https://doi.org/10.1016/j.ekir.2019.05.569
  12. L.A. M, M. H, E. R, S. C, A.-M. C, M.J. D, et al. Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy. J Obstet Gynaecol Canada [Internet]. 2008;30(3):S1–2. Available from: http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L610893256%0Ahttp://dx.doi.org/10.1016/S1701-2163(16)32776-1
  13. Prakash J, Ganiger VC, Prakash S, Iqbal M, Kar DP, Singh U, et al. Acute kidney injury in pregnancy with special reference to pregnancy-specific disorders: a hospital based study (2014–2016). J Nephrol [Internet]. 2018;31(1):79–85. Available from: http://dx.doi.org/10.1007/s40620-017-0466-y
  14. Kivai, Jayne Mueni; Kayima, Joshua; Were AJO; Quereshi Z. Assessment Of Characteristics Of Patients With Pregnancy Related Acute Kidney Injury In Kenyatta National Hospital. J Kenya Assoc Physicians [Internet]. 2019;2(2):57–61. Available from: http://41.204.161.209/handle/11295/107142
  15. Conti-Ramsden FI, Nathan HL, De Greeff A, Hall DR, Seed PT, Chappell LC, et al. Pregnancy-related acute kidney injury in preeclampsia: Risk factors and renal outcomes. Hypertension. 2019;74(5):1144–51.
  16. Kabbali N, Tachfouti N, Arrayhani M, Harandou M, Tagnaouti M, Bentata Y, et al. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study. Saudi J Kidney Dis Transplant. 2015;26(3):619.
  17. Goplani K, Shah P, Gera D, Gumber M, Dabhi M, Feroz A, et al. Pregnancy-related acute renal failure: A single-center experience. Indian J Nephrol. 2008;18(1):17.
  18. Randeree IGH, Czarnocki A, Moodley J, Seedat YK, Naiker IP. Acute Renal Failure in Pregnancy in South Africa. Ren Fail [Internet]. 1995 Jan 1;17(2):147–53. Available from: https://doi.org/10.3109/08860229509026251
  19. Belay AS, Wudad T. Prevalence and associated factors of pre-eclampsia among pregnant women attending anti-natal care at Mettu Karl referal hospital, Ethiopia: cross-sectional study. Clin Hypertens. 2019;25(1):1–8.
  20. Fokom-Domgue J, Noubiap JJN. Diagnosis of hypertensive disorders of pregnancy in sub-Saharan Africa: A poorly assessed but increasingly important issue. Vol. 17, Journal of Clinical Hypertension. 2015. p. 70–3.
  21. Noubiap JJ, Bigna JJ, Nyaga UF, Jingi AM, Kaze AD, Nansseu JR, et al. The burden of hypertensive disorders of pregnancy in Africa: A systematic review and meta-analysis. Vol. 21, Journal of Clinical Hypertension. 2019. p. 479–88.
  22. Tomimatsu T, Mimura K, Endo M, Kumasawa K, Kimura T. Pathophysiology of preeclampsia: An angiogenic imbalance and long-lasting systemic vascular dysfunction [Internet]. Vol. 40, Hypertension Research. Nature Publishing Group; 2017. p. 305–10. Available from: http://dx.doi.org/10.1038/hr.2016.152
  23. Manzoor H, Bhatt H. Prerenal Kidney Failure [Internet]. StatPearls. StatPearls Publishing; 2020 [cited 2022 Mar 5]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560678/
  24. Mehrabadi A, Liu S, Bartholomew S, Hutcheon JA, Magee LA, Kramer MS, et al. Hypertensive disorders of pregnancy and the recent increase in obstetric acute renal failure in Canada: Population based retrospective cohort study. BMJ [Internet]. 2014;349(July):1–12. Available from: http://dx.doi.org/doi:10.1136/bmj.g4731
  25. Munib S, Khan SJ. Outcomes of pregnancy related acute renal failure. Rawal Med J. 2008;33(2):189–92.
  26. 2020 W. World Malaria Report 2020 [Internet]. Vol. 73, Who. 2020. 1–4 p. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2020
  27. Boulet SL, Okoroh EM, Azonobi I, Grant A, Craig Hooper W. Sickle cell disease in pregnancy: Maternal complications in a medicaid-enrolled population. Matern Child Health J. 2013;17(2):200–7.
  28. Rasul FB, Kalmus O, Sarker M, Adib HI, Hossain MS, Hasan MZ, et al. Determinants of health seeking behavior for chronic non-communicable diseases and related out-of-pocket expenditure: Results from a cross-sectional survey in northern Bangladesh. J Heal Popul Nutr. 2019;38(1):1–14.





Medical Journal of Zambia, Vol 49, 2

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