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A prospective post-partum evaluation of renal function in preeclampsia

It is a multisystem disease and several organs are affected at different stages of disease. Haematological changes associated most commonly is thrombocytopenia, haemolysis and intravascular coagulation. Commonly affected systems are renal system (manifested by reduced GFR, proteinuria, hyperuricemia and occasionally oliguria), liver (manifested by elevated transaminases with or without epigastric and right upper quadrant pain), and the brain (manifested by headaches, transient visual disturbances due to occipital lobe ischaemia and rarely convulsions, i.e. eclampsia). All this leads to increased maternal morbidity. Major maternal complications include HELLP syndrome, DIC, acute renal failure, placental abruption, pulmonary oedema, cardiac arrest and cerebral haemorrhage. The most common cause of ABSTRACT

maternal death is intracranial haemorrhage, which is usually secondary to severe systolic BP and acute renal failure due to abruptio placenta. The risk of death is higher in women developing antepartum eclampsia. 3 Preeclampsia accounts for a third of acute kidney injury occurring in advanced pregnancy, with high risks of progression to end-stage renal disease (ESRD). 4 The renal involvement in preeclampsia resulting in glomerular endotheliosis which is characterized by proteinuria and renal failure. After delivery, hypertension, proteinuria and renal failure are expected to resolve progressively. 5 However, hypertension and proteinuria can persist for years after delivery, necessitating further investigations for possible underlying renal disease. Meanwhile, renal failure highly correlates with blood pressure levels and renal function usually assumes the normal range within postpartum. 6 Follow-up of women after delivery has been less-than-optimal in most of the studies. Therefore, knowledge of the long-term outcomes of preeclampsia among Indian women remains limited. However, microalbuminuria without impairment of renal function has been found several years after pregnancies complicated by preeclampsia suggesting persistent endothelial damage at least in some cases. [7][8][9] This study was conducted to monitor the time-trend in blood pressure levels, renal function and proteinuria from antenatal period, six weeks postpartum and three months postpartum in women with preeclampsia delivering in Government Medical College, Thrissur, department of obstetrics and gynecology. The presence of proteinuria after pregnancy complicated by preeclampsia have value in predicting future development of chronic hypertension, residual renal abnormality or underlying vascular disease. 10

METHODS
This was a prospective study. This study was conducted for 1 year from 1 st November 2018 to 31 st October 2019. Patients included were those diagnosed to have preeclampsia attending in department of obstetrics and gynecology, Thrissur Medical College, Kerala and subsequently delivering at our institution. The study was carried out in department of obstetrics and gynecology, Government Medical College, Thrissur. This hospital is a tertiary care referral center for Thrissur, Palakkad and Malappuram districts.

Inclusion criteria
Blood pressure more than 140/90 mmHg and proteinuria >300 mg/24 hour after 20 weeks of pregnancy was included in this study.

Exclusion criteria
Patients with preexisting kidney or liver disease, patients diagnosed to have multiple pregnancy, patients with any preexisting malignancies, patients with preexisting autoimmune or connective tissue disorders, patients who were lost to follow-up, not willing to give consent were excluded from the study.

Sample size
Fisher's formula for sample size determination is used for sample sizing.
Z=1.96 Absolute precision is taken as 5%. In authors institution total number of deliveries in this 1 year was 2713 of which there were 206 cases of preeclampsia. After fulfilling the inclusion exclusion criteria 118 patients were taken as study sample. In this observational study 118 women with preeclampsia who were evaluated and managed at Government Medical college Thrissur were recruited. An informed consent form was obtained from the subjects. The study protocol was approved by institutional ethics committee. For each eligible participant, authors collected clinical and laboratory data from third trimester of antenatal period (one day before delivery and 6 weeks and three months after delivery). Clinical data include age, BMI, systolic and diastolic blood pressure, pregnancy characteristics (gravidity, parity, gestational age, mode of delivery, gestational age at preeclampsia detected, gestational age of delivery, socioeconomic status, educational status of patient, birth weight and outcome, sex of the baby. Laboratory data included blood urea and serum creatinine, urine PC ratio. Secondary variables were derived from primary variables using validated formulas. Estimated glomerular filtration rate (eGFR) was based on the Cockroft-Gault formula. 11

Statistical analysis
The collected data was coded and entered in MS excel and analysed using appropriate statistical procedure (SPSS software). The statistical significance was ascertained by p value <0.05.

RESULTS
A total of 118 patients were followed up in this 1-year long study. The following variables were studied Maximum number of patients were from the age group of 21-30 years, amounts to 67.8% and mean age was 26. Mean BMI in non-severe preeclampsia was 24.56, severe preeclampsia group was 25.67 which was significant. Mean gestational age at detection of preeclampsia and delivery were 32.6 and 36.1 respectively (Table 1).    Mean birth weight was 2.17 kg and on comparing birth weight between non severe preeclampsia and severe preeclampsia group, birth weight was 2.23 and 2.05 respectively which was statistically significant. Majority of patients delivered vaginally (55.9% term deliveries and 27.1% preterm deliveries), 16.9% ended in LSCS.
Blood urea levels were normal after post-partum in both groups. By postpartum, creatinine values became normal in both the groups. By postpartum, GFR values became normal in both the groups.
In severe preeclampsia group, proteinuria was persisting even after 3 months whereas proteinuria resolved completely in non-severe pre-eclampsia group.
Systolic BP came to normal value by 6 weeks postpartum for non-severe preeclampsia group, where as in severe preeclampsia group it took 3 months.  Diastolic BP came to normal value by 6 weeks postpartum for non-severe preeclampsia group, where as in severe preeclampsia group it took 3 months.

DISCUSSION
Majority of the patients were in the age group 21-30 and constituted 67.8%. Mean age was 26.9 and 25.8 for nonsevere and severe preeclampsia respectively. This is similar to study of Saini et al which was 26.3 and 27.2. 12 Mean BMI of the study was 24.5 kg/m 2 and 25.6 kg/m 2 respectively for non-severe and severe preeclampsia. BMI in severe preeclampsia group is slightly less than the study of Saini et al which was 27.6 kg/m 2 . Mean gestational age at which preeclampsia diagnosis made were 32.7 weeks and 32.4 weeks respectively for nonsevere and severe preeclampsia.
In this study, preeclampsia was more common in primigravida's accounts to 57.6%. The present finding of increased incidence of pre-eclampsia in primigravida's was in agreement with the study conducted by Kumar P et al and Sajith et al study, where 61% and 53.8% of preeclampsia cases were of primigravida's. 13 Patients those who were on antihypertensives was 94.9%, which may be because of better health accessibility in Kerala.

CONCLUSION
For most of the women, hypertension will resolve within the 1st week after delivery. Hypertension that persists more than 6 weeks postpartum usually represents a pathology not directly associated with pregnancy such as essential hypertension or underlying endocrine, neurological, or renal disease. These women should have their hypertension confirmed with ambulatory monitoring and referred for investigation for a secondary cause for their hypertension. Proteinuria that persists beyond 6-12 weeks postpartum may also warrant further investigation, particularly in early onset preeclampsia, the group of women most likely to have underlying renal disease.