Native kidney biopsy in pregnancy and postpartum: A single centre experience from India

Abstract

Background

With the advances in medicine and imaging, renal biopsy is increasingly utilised for identifying pathologies during pregnancy.

Methods

This retrospective observational study aimed to assess indications and complications among 32 women who underwent native renal biopsies during pregnancy and postpartum from 2015 to 2022.

Results

The commonest indications for performing the biopsy were nephrotic syndrome and acute kidney injury during pregnancy or immediately postpartum. Most (62.5%) had biopsies performed in the antenatal period. Lupus nephritis was the most common finding on biopsy, and there were no procedure-related serious adverse effects. Most pregnancies were complicated by hypertensive disorders and preterm birth. All except six women with perinatal loss had healthy neonates.

Conclusions

Even as kidney biopsy remains the gold standard for diagnosing renal pathologies, it should be reserved for women where management in pregnancy would be altered by the result.

Keywords

Renal biopsy proteinuria kidney biopsy kidney disease preeclampsia pregnancy

Introduction

During pregnancy, the kidneys undergo pronounced haemodynamic, structural, and endocrine changes, and some disorders are known to flare during pregnancy.^1,2 This can lead to clinical manifestation or unmasking of underlying kidney disease, presenting with significant proteinuria, active sediment in urine (presence of red blood cells or casts), raised creatinine, and some presenting with hypertension.^1,3 It is sometimes difficult to distinguish the various pathologies from the pregnancy-specific complications, such as preeclampsia, by clinical presentation alone. Pregnancy provides a window of opportunity for early identification and initiation of appropriate treatment, as many women may otherwise only present again in a subsequent pregnancy or with advanced renal failure at a later age.^2,4

The biopsy indications and pregnancy duration dictate the start of treatment and prognosis.^5,6 Even as the risk of complications such as haemorrhage increases from pregnancy-related hemodynamic changes, using image-guided procedures has reduced such complications in recent years.^7–10 There have been improvements in child and mother survival rates since early diagnosis and treatment were instituted.^8,11,12; shown to have therapeutic advantages in 66% of cases in earlier reports.^11,13 This study aimed to gather information regarding the indications and complications during the renal biopsies performed during pregnancy and postpartum procedures.

Material and methods

This retrospective observational study was conducted at Women and Children Hospital, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India, from January 2015 to August 2022. Ours is a tertiary care and referral centre in the southeastern region of India, primarily catering to the rural population belonging to the state of Puducherry and nearby districts of Tamil Nadu. Women who had undergone native renal biopsy during pregnancy and postpartum were identified from the biopsy register maintained in the Departments of Nephrology and Pathology, and their hospital admission files were retrieved from the medical records department. The study protocol and the waiver of consent were approved by the Institute Ethical Committee (Human Studies). (vide No. JIP/IEC/2022/099).

The Nephrology department maintains a registry for native kidney biopsies, which prospectively records details related to kidney biopsies like demographic data, indication for biopsy, lab reports, details of biopsy procedure like the size of the biopsy needle, number of passes, cores obtained and post-biopsy complications. Data such as age, medical comorbidities, parity, previous history of pregnancy loss, obstetric complications such as anaemia, hypertensive disorders of pregnancy, placental abruption, and labour/ delivery details and neonatal outcomes were also collected. The investigation reports, such as haemoglobin, serum creatinine, and proteinuria, as well as reports of autoimmune disease screening with antinuclear antibody testing and complement levels, if available, were noted from the records. Biopsy-related complications requiring interventions like intravenous fluids, blood transfusion or invasive procedures to stop bleeding (e.g. angioembolisation) were considered ‘serious adverse effects’.

Statistical analysis

Data were analysed using STATA 17.0 (Stata Corp, USA). The normality of the continuous variables was tested, and continuous data such as age, gestational age at diagnosis, etc., were presented as mean with standard deviation or as median with range. Categorical data, such as indication, parity, histopathological diagnosis etc. were presented as frequencies and percentages.

Results

Thirty-two women who underwent renal biopsy during pregnancy or postpartum were included during the study period (Table 1). The majority of them were multiparous women (n = 22, 68.7%). Pregnancy loss in the past, either spontaneous miscarriage or later in-utero fetal death, was observed in 13 (40.6%) cases. Fifty per cent of the cases had one or more medical comorbidities, and chronic hypertension was the most common. The mean gestation age at presentation was 27.8 weeks, with seven cases (21.8%) presenting at a gestational age less than 20 weeks. All (n = 32) had mild to moderate anaemia, with eight diagnosed with severe anaemia requiring blood transfusions. Acute kidney injury (AKI) developed in eight cases, four requiring renal replacement therapy.

The indications for renal biopsy were nephrotic-range proteinuria (18,56.3%), AKI (8, 25%) and suspected chronic kidney disease (12, 37.5%). Thirteen of the 18 women with nephrotic syndrome had autoimmune serology positivity. Twenty renal biopsies were performed in the antenatal period, with a mean gestational age of 23.1 weeks and 12 in the immediate postnatal period. All biopsies were done in real-time ultrasound guidance, with the majority performed using 18G needle (n = 20, 68.8%) and 26 (81.2%) requiring three or more passes of the needle. Only two cases had procedure-related complications, and both were performed in the post-partum period. One woman developed a peri-renal hematoma that resolved with conservative treatment. The second patient developed a peri-renal hematoma and cellulitis of the right lower back, which recovered with a seven-day course of antibiotics (Table 2).

Table 1.

Maternal characteristics at presentation/admission to hospital.

Variable	Mean ± SD or frequency with percentage
Age, years	25.2 ± 4.5
Parity
Nulliparous	10 (31.3)
Multiparous	22 (68.7)
Previous history of p regnancy loss	13(40.6)
History of termination of pregnancy: one or more	7(21.9)
History of fetal demise (>28 weeks of gestation)	2(6.3)
History of both termination of pregnancy and fetal demise	4(12.5)
Medical comorbidities at presentation*	17(53.2)
Known connective tissue disorder	1(5.9)
Diabetes mellitus	2(11.8)
Liver disease	1(5.9)
Chronic hypertension	13(76.4)
Hypothyroidism	3(17.7)
Gestational age at presentation, weeks**	27.8 ± 8.2
Body w eight, kilograms	62.9 ± 12.3
Investigations
Serum creatinine, mg/dl
Second trimester	1.1 (0.8–1.4)
Third trimester	1.0(0.7–3.3)
Postpartum	0.9(0.6–3.3)
Blood u rea, mg/dl
Second trimester	22.5(17.0–27.0)
Third trimester	20.0(15.0–53.0)
Postpartum	21.0(17.0–29.0)
Hemoglobin level, gm/dl
Second trimester	8.2 ± 1.7
Third trimester	8.4 ± 2.4
Postpartum	9.2 ± 2.0
Urine protein creatinine ratio, gm/gm
Second trimester	2.4 ± 1.1
Third trimester	2.7 ± 1.1
Postpartum	2.4 ± 1.2
USG k idney s ize, cm	10.3 ± 0.8

*May have one or more of the comorbidities; **n = 7 presented at less than 20 weeks’ gestation.

One maternal death occurred two months after delivery in a patient who had undergone antenatal renal biopsy. She died from sepsis unrelated to the procedure. She was a multigravida under treatment before pregnancy for diabetes, hypertension, secondary antiphospholipid antibody syndrome, vitamin A deficiency, and Graves’ disease. She underwent a renal biopsy at 28 weeks while being evaluated for hypertension with nephrotic-range proteinuria (5 g/day). She had hypertensive nephropathy (stage 4 CKD) and delivered a stillborn baby (with severe fetal growth restriction) at 32 weeks of gestation. She was readmitted at three months postpartum with haemoptysis and was diagnosed with a lung abscess. She succumbed to sepsis-related complications).

Table 2.

Details of the renal biopsy and its complications.

Variable	Mean ± SD or frequency with percentage
Gestational age at biopsy (among those who had renal biopsy in the antenatal period, n = 20), weeks	23.1 ± 8.2
Needle gauge used
16G	10(31.3)
18G	22(68.8)
Number of needle passes for biopsy
1	2(6.3)
2	4(12.5)
3	19(59.4)
4	7(21.8)
Glomeruli p resent in specimen	27(84.4)
Complications
None	30(93.4)
Bleeding (hematoma)	1(3.3)
Sepsis	1(3.3)

Histopathological analysis showed lupus nephritis (LN, n = 13) as the commonest pathology, most of them having Class 3 LN (n = 10). (Figure 1) Hypertensive nephropathy(n = 6), and focal segmental glomerulosclerosis (n = 3) were the other common causes. Membranoproliferative glomerulonephritis (MPGN), IgA nephropathy, and acute cortical necrosis (ACN; following obstetric haemorrhage) were found in two cases each, and one each had thrombotic microangiopathy (TMA), acute tubular necrosis (ATN) and chronic glomerulonephritis (CGN).

Figure 1.

Final histopathological diagnosis.

Table 3.

Labor, delivery and neonatal outcomes of pregnancies among those (n = 25) who crossed the period of viability.

Variable	Mean ± SD or frequency with percentage
Gestational age at delivery, weeks	33.0 ± 4.4
Preterm b irth	16(64.0)
Mode of delivery
Vaginal delivery	8(27.6)
Caesarean section	17(58.6)
Anaestheti s e for ca esarean section (n = 17)
Spinal	15(88.2)
Epidural	2(11.8)
Blood loss during delivery, ml ( m edian with IQR)	500 (350–600)
Birth outcome
Live born	21(84.0)
Still born	4(16.0)
Birthweight, grams	2112.0 ± 0.8
Median b irth weight centile (25th—75th centiles)	26.9(2.0–98.1)
Apgar s core at 5 min* ( m edian with IQR)	8(8–9)
Admission to NICU	13(61.9)
Neonatal d eath	2(9.5)

*Excluding four stillborn babies.

Preeclampsia complicated 43.8% of the cases, with 21.9% complicated with haemolysis, low platelet elevated liver enzymes (HELLP) syndrome and 12.5% with eclampsia. Fetal growth restriction was observed in 37.8% of pregnancies. Labour, delivery and neonatal outcomes of pregnancies among those (n = 25) who crossed the period of viability are shown in Table 3. The mean gestational age at delivery, after excluding those who had a miscarriage (n = 5) and two who opted for medical termination because of kidney disease (n = 2), was 33.0 weeks, and a mean birth weight of 2112 grams (median birth centile, 26.9). Most had undergone caesarean section (n = 17, 58.6%). Four stillbirths occurred among those with fetal growth restriction and preeclampsia. Most babies require admission to the NICU because of prematurity or low birth weight. There were two neonatal deaths following complications from severe fetal growth restrictions and sepsis.

Discussion

In this largest series of kidney biopsies from India during pregnancy and postpartum, we found that nephrotic syndrome and AKI were the most common reasons kidney biopsy was performed during or immediately after pregnancy. Lupus nephritis was the most common finding on biopsy, and there were no procedure-related serious adverse effects. There was a high incidence of hypertensive disorders during pregnancy, and two-thirds of pregnancies ended in preterm birth, with the baby requiring admission to the neonatal intensive care unit. All except six women with perinatal loss had healthy neonates with a mean birth weight of 2112 grams (median birth centile 26.9).

Autoimmune disorders are frequent in women of reproductive age group, and the combination of hypertension and proteinuria in pregnancy may be the initially presenting symptoms in these women.^14,15 In such instances, additional evaluation of autoimmune serology may aid in the diagnosis. An invasive kidney biopsy may not be necessary in these women without additional complications like AKI. In women who are negative for autoimmune serology, timely biopsy will help in the diagnosis of other pathologies such as FSGS, IgA nephropathy and TMA, and may help in the initiation of specific therapy, which may potentially improve the maternal and fetal outcomes. Another challenge in choosing the pregnant women who might benefit is the similarity in presenting pregnancy-specific complications such as preeclampsia, which may even have nephrotic range proteinuria.^2,7,9–11 This led to referrals in the following 20 weeks, as is evident in the current series, where only 7 of the 32 were biopsied at less than 20 weeks of gestation. Recent reports have highlighted the possible usefulness of biomarkers in differentiating chronic kidney disease from preeclampsia. However, it needs to be validated in further studies, and the availability of such tests probably limits its use settings similar to the index study.^16,17

Hypertensive changes in the kidney were the second common pathology noted in the series. The recent systematic review of the indication and risk of renal biopsy during pregnancy and postpartum also had the hypertensive disorders associated with nephrotic syndrome as the commonest indication for the procedure.¹¹

All the biopsies were imaging-guided and performed by nephrologists, which might have helped to reduce the complication rates.^7–11 There were no serious or life-threatening complications related to the procedure. Two women had a perinephric hematoma, managed conservatively. Piccoli et al.,¹¹ in a systematic review of 39 studies, reported major complications needing blood transfusions or pregnancy losses in 2% of the cases and minor bleeding (which include small hematoma not requiring transfusion) or only microscopic haematuria in 5% among 197 renal biopsies during pregnancy and the only three minor complications among 268 biopsies in the postpartum period. In the index case series, the complications occurred in cases where the biopsy was performed in the postpartum period.

This is one of the largest series of renal biopsies performed during antenatal (n = 20) and postpartum (n = 12) from low to middle-income countries and the largest yet from India. Using the same protocol for performing biopsies over seven years, prospective entry of the procedure-related data in the renal biopsy registers and the pathologies reported by the same specialist team under the co-investigator is a strength of the study. This would have resulted in lower complication rates, helped collect the immediate procedure-related complications, and reduced reporting bias. Being a record-based study, the access was limited to the data entered in the register and the inpatient records, which might have resulted in missing information and further changes in treatment on follow-up visits. The absence of a control group and long-term follow-up limited the interpretation of the risk-benefit ratio of performing the renal biopsy during pregnancy and the improved outcomes from a change in therapy after the biopsy report was available. A prospective multicentre network is needed to evaluate its impact, even as the biopsies have become safer following image guidance for procedure and increasing technical expertise.

Conclusion

Nephrotic-range proteinuria, AKI and hypertensive disorders are the common reasons for performing kidney biopsies during pregnancy or postpartum. The most common pathology was lupus nephritis. Renal biopsy was safe in pregnancy with no serious adverse effects. Native renal biopsy may be considered after weighing the individual risk of complications of performing the procedure during pregnancy and the gestational age, against the risks of waiting until after delivery for a definitive tissue diagnosis.

Supplemental Material

sj-docx-1-obm-10.1177_1753495X241290664 - Supplemental material for Native kidney biopsy in pregnancy and postpartum: A single centre experience from India

Supplemental material, sj-docx-1-obm-10.1177_1753495X241290664 for Native kidney biopsy in pregnancy and postpartum: A single centre experience from India by Shreya Srinivas Mondemu, Sreejith Parameswaran, Rajesh Nachiappa Ganesh and Anish Keepanasseril in Obstetric Medicine

Footnotes

Acknowledgements

None

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. First Author SSM was supported by the Golden Jubilee Short-Term Research Award to undergraduate students (GJ STRAUSS award) wide proposal number JIP/UGRMC/GJSTRAUS/2022/17.

Ethical approval

All procedures performed in this study were done with the ethical standards set by the Under-Graduate Research Mentoring Committee (UGRMC) and Ethical Committee (Human Studies) following the 1964 Helsinki Declaration and its later amendments.

Informed consent

The protocol of the study and waiver of consent for collecting the details of the women from records was approved by the Institute Ethics Committee (Human Studies), JIPMER, Puducherry, India. (vide No. JIP/IEC/2022/099).

Guarantor

Anish Keepanasseril

Contributorship

AK, SSM, SP and RNG conceived the study. All authors contributed to the design. SSM and AK carried out the data collection and guarantees data integrity. AK performed statistical analyses. SP, SSM and RNG reviewed the analysis and SSM & AK wrote the first draft. All authors contributed to the revising and finalisation of the manuscript. AK (corresponding author) guarantees all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

ORCID iD

Anish Keepanasseril

Supplemental material

Supplemental material for this article is available online.

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