Obstetric acute renal failure (ARF), occurring during pregnancy or in the immediate postpartum period, is currently a declining entity, although persistent in developing countries, and provider of a significant morbi-mortality [1], so much so that it is the subject of many writings in the literature, and represents a real public health problem. Maternal mortality from all causes in Morocco was 72.6% in the period 2015-2016 [2]. Direct obstetric causes are mainly dominated by hemorrhage (36%) in the first place, followed by pre-eclampsia (19%), reflecting thus, a possible failure of antenatal monitoring systems. In our study, we are interested in the risk factors involved in the occurrence of ARF during pregnancy, to evaluate its incidence, as well as its evolutionary profile, both temporally and geographically.

We have retrospectively gathered, by means of hospitalization registers within the maternal-infantile intensive care units of the Hassan II University Hospital of Fez, 75 patients who developed AKI during their pregnancy or in the immediate postpartum period (< 03months). These cases were identified over the period from January 2017 to August 2019, and were followed by the Nephrology Department of the Hassan II University Hospital of Fez. We included in this study, any patient aged over 18 years, who presented an AKI according to the definition of the KDIGO recommendations (2017) [3], based on baseline creatinemia ( rise > 3mg/l, or >1.5 times the baseline creatinemia), and urine output (<0.5ml/kg/6h). We have substantially retained a cut-off of 12 mg/l to define AORF in the absence of the previous history. Patients with a history of renal failure or previous nephropathy were excluded from this study.

Data Collection

Numerous data were retrospectively collected both in terms of:

• Sociodemographic: Age, history of miscarriage, IUFD or pre-eclampsia, number of pregnancies/parity, prim parity, presence of associated comorbidities (diabetes, hypertension, heart disease...), reasons and duration of hospitalization.
• Clinical and biological: Blood pressure, the occurrence of seizures, volemic evaluation, haemoglobin rate, white blood cell count, platelet count, LDH, Haptoglobin, CRP, transaminases (ASAT, ALAT), albuminemia, protidemia, urea, creatinemia.
• Histological (renal biopsy): performed in cases of rapidly progressive renal failure with no obvious retained cause, or in the absence of complete renal recovery beyond six weeks.

Definitions

• In our approach, we have retained the following definitions:
• Pre-eclampsia: Appearance of arterial hypertension (>140/90mmHg) diagnosed during pregnancy beyond 20 weeks of amenorrhea, in a patient previously normotensive, associated with proteinuria of at least 300mg/24h (or >2+ on urinary dipstick).
• Severe pre-eclampsia: context of pre-eclampsia, associated with a criterion of clinico-biological severity:
• Hypertension > 160/110mmHg, persistent neurosensory symptoms of hypertension, persistent epigastric or right hypochondrium pain, pulmonary edema.
• Thrombocytopenia < 100,000el/mm3, Hepatic cytolysis defined as ASAT and ALAT levels at least twice normal.
• Acute renal failure > 12mg/l or creatinemia duplication in the absence of underlying nephropathy.
• Pregnancy hypertension: Occurrence of hypertension (>140/90mmHg) beyond 20 weeks of amenorrhea, in a previously normotensive patient, without proteinuria, nor clinico-biological manifestations of pre-eclampsia severity.
• Eclampsia: Occurrence in the context of pre-eclampsia of generalized convulsive seizures not attributed to another cause.
• HELLP Syndrome: Presence of hemolysis, hepatic cytolysis, thrombocytopenia, and possibly hypertension.
• Chronic non-pregnancy hypertension: Onset of hypertension > 140/90mmHg, diagnosed during pregnancy before 20 weeks' gestation, or persisting for at least 12 weeks postpartum.

Statistical Analysis

The statistical analysis in uni and multivariate was carried out in collaboration with the epidemiology department of the Hassan II University Hospital of Fez, using the SPSS software. We established risk factors correlated with renal evolution, considering a significance index if p<0.05. We compared in logistic regression, based on composite criteria, two groups: the first one presenting a favorable evolution marked by a normalization of the renal function, and a second unfavorable group defined either by the persistence of the renal insufficiency or the occurrence of a maternal-fetal death.

Socio-Demographics

Of the 492 hospitalizations reported over the period of our study in the materno-fetal resuscitation unit, 371 patients were admitted either during pregnancy or in the immediate postpartum period. Among them, 75 patients were selected as having renal failure meeting our inclusion criteria, i.e. a prevalence of 20.2%. The mean age of our patients was 31.09 ± 6.74 years [18 - 43 years], of which 65.3% (n=49) were in the pregnancy period with a mean term of 31 +/-6 [6 - 38SA] against 34.7% (n= 26) parturients. 16 patients were primiparous (21.3%), against 16% for whom parity could not be determined. 27.4% had a history of miscarriage and 10.7% had a history of pre-eclampsia. Oligo-anuria was initially identified in 22 patients (29.3%). The average length of hospitalization was 7 days ±7 [0-44]. All socio-demographic and clinical characteristics were summarized in (Table 1).

Table 1: Socio-demographic and biological characteristics of obstetric ARF in our series.

 Biological 

Based on the KDIGO 2017 classification, 45.3% of patients with renal failure were classified as stage 3, compared with 26.5 and 28% for stages 1 and 2, respectively. The mean creatinemia was 27.8mg/l ± 18.7 [12-129]. Anemia (Hb<10g/l), thrombocytopenia and hepatic cytolysis were noted in 61.3%, 82.6% and 12% of cases respectively.

Causes of Acute Renal Failure 

The most common etiology was preeclampsia (46.7%), followed by hemorrhage (24%) and sepsis (13.3%) (Figure 1). The main complications associated with pre-eclampsia were mainly eclampsia, followed by HELLP syndrome with respective rates of 41.3% and 31%. Renal biopsy was performed in one patient, indicated in the face of persistent renal failure, after a delay of 169 days, revealing acute post-infectious glomerulonephritis (APIG).

Figure 1: Etiology of acute renal failure in the setting of pregnancy or postpartum.

Therapeutic Management 

The therapeutic management was focused on volemic optimization mainly by vascular filling using crystalloids (50.6%), followed by the use of loop diuretics at significant dose (>500mg/d) as well as vasoactive drugs respectively in 32% and 30% of cases. Hemodialysis was started in 16% of cases, mostly indicated for anuria (66%), and overload (16.7%).

Evolution

36 patients (48%) progressed to normalized renal function at discharge, with a mean time to normalization of 5.66 Days [1-52]. Of the 39 remaining patients, two progressed to chronic disease at 03 months (one of them was put on long term hemodialysis), the others had renal failure at discharge but were subsequently lost to follow-up (Figure 2). Maternal mortality was 24% (n=18). Fetal mortality was 20%.

Figure 2: Overall evolution of prevalent patients during the study period.

Statistical Analysis

In univariate analysis (Khi-2 test), a pre-existing heart disease, pre-eclampsia as a cause of AKI, an initial preservation of urine output, and the use of vasoactive drugs are all factors associated with maternal survival. Creatinemia at admission and the use of vasoactive drugs were associated with a poor outcome (Table 2).

Table 2: Factors influencing renal and maternal outcome in our study.

Obstetric ARF, although becoming rarer in developing countries especially in Europe, continues to persist in an ad hoc and periodic manner [4]. Numerous theories have been put forward to explain this persistence, which is still minimal, and seem to focus on the re-emergence of certain etiologies such as haemorrhagic causes due to changings in obstetrical practices involving the use of fibrinolytics (tranexamic acid and its implication in the occurrence of renal cortical necrosis [5]), and the predisposition of a certain category of patients (diabetics, hypertensives or patients with chronic renal insufficiency) to pre-eclampsia. It would also be partly explained by the legalization of abortion since the 1970s. In Morocco, the downward trend in maternal mortality from 112 (2009-2010) to 72.6 (2015-2016) per 100,000 births (i.e., a reduction of 35%) argues in favor of strengthening antenatal care structures, which nevertheless remain quite inadequate [2]. In comparison with the data from our series, the average age of onset of ARF (during pregnancy or in the post-partum period) seems to be comparable with that found in the literature, whether in other Maghreb countries [6-11], in Asia [12,13], or in South Africa [14] not exceeding 30 years on average (Table 3). Only the works of Kabbali [8] and Arrayhani [10] have significantly associated age with an unfavorable evolution. In the other papers [15], age is associated with many perinatal complications, including preterm delivery. The results concerning primiparity seem to be more variable, with rates not exceeding 48% in the Maghreb countries, and exceeding 50% in China. In the studies compared, AORF was mainly diagnosed during pregnancy, particularly during the 3rd trimester. Only in the study conducted by the Kabbali team [8] did we note a clear predominance of ARF in the postpartum period (52.3%). The prevalence of oligo-anuria is variable from one study to another, not exceeding on average 50% (Table 3). The main causes of ARF accross different studies are pre-eclampsia, sometimes representing 75% of all causes, followed closely by haemorrhagic causes, while infectious causes remain less significant. From a temporal point of view, limiting ourselves to the etiological profile of ARF in the regions of Morocco, we note a downward trend in the frequency of pre-eclampsia, although it remains the predominant etiology (Table 3).

Table 3: Summary of the epidemiological characteristics of obstetric ARF with review of the literature.

Sepsis was significantly correlated with unfavorable outcome in the work of Kabbali (p=0.06) [8], whereas in our series, pre-eclampsia as an etiology was correlated with complete renal recovery (p=0.018). Therapeutic management is focused on volume control to improve renal hemodynamics. In our series, there was a clear predominance of the use of vasoactive drugs with a rate of 30.6% compared to other Moroccan studies where the respective rates were 11 and 5.4% [8-11]. This could be due to a selection bias possibly related to the exclusive recruitment of our patients in intensive care settings. The use of intermittent hemodialysis in our country seems to be less important with a current rate of 10.6% compared to 72.6% [11] in 2001 and 38.6% [8] in 2011, which could argue in favor of an earlier and optimized management of AKI complications. The rates in Egypt [7] and India [12] seem significantly higher at 35 and 47% respectively. The rate of complete renal recovery in our series is 48%, whereas it is around 60% in other studies (Table 4).  The work of Liu [13] have retained many factors as being associated with the occurrence of renal failure, namely sociodemographic parameters (gestational age, rural origin), biological parameters (platelet count, blood urea, creatinemia, LDH), and related to the unfavorable evolution of the pregnancy (MFIU, prematurity, IUGR, and Apgar score at 01min). Maternal mortality in the studies remains variable between 6 and 12%, against 24% in our series (Table 4). The Egyptian teams [7] have retained the occurrence of shock, hepatic cytolysis and coagulopathy as factors incriminated in the unfavorable maternal evolution. Other studies [16] were interested in the identification of blood markers involved in the renal evolution in pre-eclampsia, retaining SDF-1 as significantly associated with renal recovery.

Table 4: Comparison of renal and maternal-fetal outcome of obstetric ARF in the Marghreb countries and internationally.

Obstetric ARF, although rare, remains a subject of interest because of its implication in maternal mortality in developing countries. Primary prevention based on early detection, close monitoring of pregnancies, and delivery in a medical environment, remains the most effective and least expensive solution.

Strengths/Weaknesses of the Study

• Selection bias concerning the recruitment of patients exclusively in the intensive care unit, explaining, on one hand, the more significant maternal mortality, as well as the percentage of evolution towards a chronic renal failure, taking into account the gravity of the initial picture.
• Better optimization and monitoring of the patients' blood volume explains the lesser recourse to dialysis in our study.
• The lack of data concerning the fetal outcome remains disappointing because it could be involved in the renal outcome.

The authors declare no relationship of interest.

I would like to express my deep gratitude to Professor Sqalli Houssaini Tarik and Professor Kabbali Nadia, my research supervisors, for their patient guidance, enthusiastic encouragement and useful critiques of this research work. I would also like to thank Pr. Harandou and Pr. ElBerdai of the intensive care unit for their assistance in conducting this research. My grateful thanks are also extended to the ERESS laboratory. Finally, I wish to thank my parents for their support and encouragement throughout my study.

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