Maternal, Fetal, and Kidney Outcomes of Viable Pregnancies in Women with Underlying Kidney Disease: Experience from a Single Tertiary Care Center in India

Introduction

The management of pregnancy in a woman with underlying kidney disease is challenging. Globally, almost 3% of pregnant women are affected by kidney disease.¹ With the advances in nephrology and obstetric care, the outcome of pregnancies in such women, including those on dialysis has improved. There are no data from developing countries on the outcomes of such pregnancies. Our center, a large tertiary educational referral center in South India, handles high-risk pregnancies. This study aims to derive data on the outcome of pregnancies in women with preexisting kidney disease, which may help physicians provide effective pre-pregnancy counseling and management as well as improve the maternal, perinatal, and renal outcomes of pregnancies with kidney disease.

Materials and Methods

This study was approved by the Institutional Review Board (IRB number 14741 dated 29.06.2022). This was a single-center retrospective observational study conducted in the Department of Nephrology and Obstetrics at the Christian Medical College Vellore, one of India’s largest healthcare centers. All consecutive viable pregnancies (more than 22 weeks of gestational age) in women with underlying kidney disease, who delivered at our center between January 2012 and December 2021 were included. Only those women diagnosed with kidney disease before pregnancy or in the first trimester were included. The estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) formula² and the kidney disease improving global outcomes (KDIGO) criteria was used for defining chronic kidney disease (CKD).³

Viable pregnancy was defined according to the American College of Gynaecology (ACOG) criteria as pregnancy after 22 weeks of gestation. Gestational hypertension was defined as a new onset of hypertension (systolic blood pressure >140 mm Hg and diastolic blood pressure >90 mmHg on two occasions at least four to six hours apart). Preeclampsia and eclampsia were defined as per the ACOG criteria.⁴

The World Health Organization (WHO) criteria were used to define preterm birth as live birth before 37 weeks of gestation, while low birth weight was defined as birth weight of less than 2500 g at the time of birth, regardless of the gestational age.

The data on baseline characteristics, demographic details, and obstetric details were obtained from a prospectively maintained pregnancy data registry at the Department of Obstetrics and Gynaecology at our center. The data on kidney function, native kidney disease, clinical characteristics, treatment details, and follow-up were collected from the electronic medical records; these records were reviewed for follow-up till December 2022.

Results

Data on 201 viable pregnancies in women with underlying kidney disease were collected, which constituted 0.14% of a total of 138,110 deliveries during the study period. The mean age (±SD) at conception was 27.4 (±4.6) years, and 44.3% were primigravida. The most common clinical kidney syndrome at the initial presentation was CKD (34.8%), followed by nephrotic syndrome (32.8%). Hypertension at the time of conception was present in 23.9% of the women.

Lupus nephritis (LN), with or without antiphospholipid antibody (APLA) syndrome (39.3%), and immunoglobulin A (IgA) nephropathy (11.4%) were the common underlying kidney diseases among our patients. Renal disease was detected first during the first trimester in 40 (19.9%) pregnancies. Other baseline characteristics are summarized in Table 1.

Kidney outcomes

The mean eGFR at the time of conception was 101.2 (±33.9) mL/min/1.73 m². There was an increase in eGFR of 6.9% and 11.1% in the first and second trimesters, respectively, as compared to the pre-pregnancy level, indicating less than the expected increase in eGFR in normal pregnancy [Table 2]. The eGFR at the last follow-up was comparable to the pre-pregnancy level [Figure 1]. Seven patients (3.5%) required kidney replacement therapy at a median time of 32 (7,72.5) months of follow-up. The median (IQR) proteinuria before conception was 110.5 mg/day (80,325). There was a progressive increase in proteinuria during pregnancy, reaching a maximum in the postpartum period, which then decreased to a median (IQR) proteinuria of 205 mg/day (110,1068) at the last follow-up [Figure 2]. The physiologic fall in blood pressure, observed in normal pregnancy, was not observed in these patients.

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Figure 1:

Boxplot showing the renal function in terms of median eGFR before pregnancy, at first trimester, second trimester, third trimester, postpartum and at the last follow up. eGFR: estimated glomerular filtration rate.

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Figure 2:

Boxplot showing the renal function in terms of median proteinuria before pregnancy, at first trimester, second trimester, third trimester, postpartum and at the last follow up.

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Discussion

This study demonstrates that kidney disease in a pregnant woman is associated with worse maternal and fetal outcomes compared to those without renal dysfunction. This is the first study of such a large sample size from a developing country. The prevalence of kidney disease in pregnant women in our study was 0.14%, although the estimated prevalence of kidney disease among women of childbearing age is 3%. This may be probably due to the hesitancy among the young women and the treating physicians to continue with such high-risk pregnancies and because we have included only viable pregnancies in our study.⁶

The physiological increase in the GFR and fall in blood pressure was less than expected in a normal pregnancy.⁷ About a quarter of patients were known to be hypertensive at conception, similar to the previous studies, which reported a range between 9-40%.⁸

Our study had LN as the most common underlying kidney disease unlike previous studies which reported IgAN as the most common kidney disease in pregnant women.^8,9 Both these kidney diseases constituted more than 50% of the underlying kidney diseases reflecting the distribution of these diseases in childbearing age.

Gestational age at delivery and birthweight were lesser than the previous studies from the developed world. Our study also found higher proportions of hypertensive disorders and LSCS rates. Neonatal ICU care and infants death were more common in our study.^10-12 However, maternal death was much less in the present study. Racial and socioeconomic factors and difference in the referral practices would have resulted in these outcomes.

Although some studies have indicated that the type of glomerular disease affects the pregnancy outcome, our study failed to demonstrate any significant difference in the outcome between different glomerular diseases.¹³ This finding is consistent with the results of recent studies.^8,14,15 However, the largest subgroup (LN) had more than twice the rates of hypertensive disease, preterm births, low birth weight deliveries and higher LSCS deliveries compared to the normal pregnancies during the same period. The figures were higher than that found in similar studies.^16,17

The second largest subgroup (IgA nephropathy) also had worse maternal and fetal outcomes.¹⁴

An important finding was that as the level of proteinuria increased and renal function worsened in terms of estimated glomerular filtration rate, there was a statistically significant increase in the adverse maternal and fetal outcomes irrespective of the underlying cause – a finding consistently seen in the previous studies.^10-12,18 It highlights the fact that women with mild kidney dysfunction and lesser proteinuria may have favorable pregnancy outcomes.¹⁹

A meta-analysis by Zhang et al.¹² and other studies on kidney disease in pregnancy have shown that long term renal outcome is favorable.^10,20 Our study also showed stable kidney function following pregnancy as evidenced by the stable GFR and proteinuria on long term follow up. This is an important finding as the main concern for the nephrologist is the possibility of deleterious effect of pregnancy on the long-term kidney function. However, our cohort had lesser women with eGFR less than 30 ml/minute/1.73 sq.m and nephrotic range proteinuria which needs further evaluation.

Our study also has shown that women on renin angiotensin aldosterone (RAAS) inhibitors at the time of conception did not have any fetal abnormalities similar to the finding shown in a study by Bilal et al.²¹ This finding is important as some nephrologists may advise termination of pregnancy in such women rather than withholding the drug and continuing the pregnancy.

Our study had only 6 kidney transplant patients. Although reliable conclusions cannot be drawn because of smaller sample size, our study showed worse pregnancy outcome as shown by Deshpande et al.²² Contrary to the findings of the metanalysis by Marleen C. van Buren and a prospective study by Aivazoglou et al. our patients had poor kidney outcome with half of the patients having a GFR of less than 20 ml/min/1.73m² on long term follow up.^23,24

Successful pregnancies in women on dialysis are being reported from worldwide.²⁵ However our study did not have any patients on dialysis reflecting low fertility rates and the hesitancy of the patient and physician.

Our study had a few limitations: It was a single-center study. We used the CKD-EPI equation to estimate GFR, which had not yet been validated in pregnancy. There were no women on dialysis. Despite the limitations mentioned above, it was the largest study reported from a developing country like India.

In conclusion, women with underlying kidney disease, including those with reasonably good kidney function at conception had worse pregnancy outcomes compared to the normal pregnancy. However, long-term kidney outcomes were favorable.