Pregnancy-associated acute kidney injury as a hidden driver of Chronic kidney disease in developing countries

doi:10.21203/rs.3.rs-5192861/v1

Download PDF

Research Article

Pregnancy-associated acute kidney injury as a hidden driver of Chronic kidney disease in developing countries

https://doi.org/10.21203/rs.3.rs-5192861/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Introduction:

Pregnancy-related AKI (PR-AKI), has profound maternal and fetal implications, including high mortality and long-term risks such as the development of chronic kidney disease (CKD). This systematic review aims to evaluate the burden of CKD owing to PR-AKI cases during follow-up in developing countries, particularly India.

Methods:

A systematic search of PubMed, Embase, and Cochrane databases was performed for Indian studies published between 2000 and June 2024. We included cross-sectional, retrospective, and prospective cohort studies that reported the incidence of PR-AKI, subsequent CKD, and dialysis dependency in Indian cohorts during follow-up. Details of etiology of PRAKI, and adverse fetal and maternal outcomes were also recorded. Only studies that provided follow-up kidney outcomes were considered.

Results:

A total of 25 studies comprising 2,306 participants were included in the analysis. The incidence of PR-AKI ranged from 1–12%. Sepsis was the most common cause of PR-AKI, accounting for up to 78% of cases, followed by hypertensive disorders, obstetric haemorrhage, and tropical etiologies. Hemodialysis was required in 20–85% of patients. CKD development during follow-up was observed in 12.8–35% of cases, with up to 30% remaining dialysis-dependent. Maternal mortality ranged from 2.5–34%, while perinatal mortality reached as high as 67.3%. Pre-term delivery rates varied between 13.9% and 58%.

Conclusions:

Up to one-third of PR-AKI patients may develop CKD and remain dialysis-dependent during follow-up. PR-AKI significantly impacts both maternal and fetal morbidity and mortality. Early prevention and prompt management by healthcare professionals are critical to improving outcomes in PR-AKI.

Pregnancy-related acute kidney injury (PR-AKI) significantly affects maternal and fetal health, leading to high mortality and long-term complications such as chronic kidney disease (CKD). This systematic review, focusing on developing countries like India, evaluated the burden of CKD due to PR-AKI patients. The review analyzed Indian studies published between 2000 and June 2024, including 25 studies with 2,306 participants. PR-AKI incidence ranged from 1% to 12%, with sepsis being the leading cause in up to 78% of cases, followed by hypertensive disorders, obstetric hemorrhage, and tropical fevers. RRT was needed in 20% to 85% of patients, and 12.8% to 35% developed CKD during follow-up, with up to 30% remaining dialysis-dependent. Maternal mortality varied from 2.5% to 34%, while perinatal mortality reached 67.3%. The study emphasizes the critical need for early prevention timely intervention and need for long-term follow-up to reduce the high morbidity and mortality rates associated with PR-AKI.

Pregnancy-related acute kidney injury (PRAKI) represents a critical cause of maternal and fetal morbidity and mortality, particularly in developing countries. While its epidemiology varies globally, the burden remains disproportionately high in low- and middle-income regions, where healthcare access and resources are limited. (1) The maternal mortality in PRAKI is as high as 25%. (2) Despite recent improvements in maternal care, India still grapples with a significant incidence of PRAKI, which contributes to long-term complications such as chronic kidney disease (CKD and stage kidney disease (ESKD). PRAKI not only threatens immediate maternal outcomes but also serves as a hidden driver of CKD, adding to the existing healthcare burden in a country already witnessing an epidemic of CKD. (3) Moreover, the long-term repercussions of PRAKI are profound, as up to 30% of survivors develop CKD, and 20% may remain dialysis-dependent. (4) In India, the incidence of PRAKI has shown a steady decline over the past decades—from 22% in the 1960s to 3–7% in the 2000s—primarily due to enhanced antenatal care, a reduction in septic abortions, and better management of obstetric complications such as anti and postpartum hemorrhage. (5) According to recent data from the Indian Society of Nephrology (ISN) registry, obstetric complications account for 5% of total AKI cases, highlighting the persistent significant national health issue. (6) The evolving landscape of PRAKI in India shows a shift from traditional causes like septic abortion to emerging drivers such as hypertensive disorders, preeclampsia, and thrombotic microangiopathies (TMA). These complications, which arise predominantly in the later stages of pregnancy, continue to pose diagnostic and therapeutic challenges. (7) Conditions such as acute fatty liver of pregnancy (AFLP), hemolysis, elevated liver enzymes, low platelets (HELLP syndrome), and puerperal sepsis also contribute to the risk of AKI, complicating both maternal and fetal outcomes. The significant incidence of PRAKI, along with a substantial number of women developing CKD highlights the significance of understanding PRAKI's contribution to the rising CKD epidemic among women in developing countries such as India.

Given the significant variability in PRAKI incidence and outcomes across different regions in India, there is a critical need for a systematic review of Indian studies. By analyzing the evolving etiological patterns, risk factors, and long-term consequences, more precise strategies for early diagnosis and intervention can be developed. Furthermore, as India progresses towards adopting advanced diagnostic tools such as genetic analysis, identifying complications like TMA, preeclampsia, and HELLP syndrome can lead to better-targeted therapies, ultimately improving maternal and fetal health outcomes

Inclusion Criteria

We included studies that reported kidney outcomes in women following and AKI episode during PRAKI in India. Only studies published as full-text articles and providing data on kidney outcomes were included. Eligible studies included cohort studies, randomized control trials, case-control studies, and cross-sectional studies, with the exception of in vitro studies, letters to the editor, review articles, editorials, and short communications. Articles published in languages other than English and outside India were also excluded.

The study adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines. (8) The systematic review protocol is registered in PROSPERO (registration number: CRD42024576213; http://www.crd.york.ac.uk/PROSPERO). Prisma checklist of the systematic analysis is provided in supplementary material 2.

Data Search

A comprehensive literature search was conducted across EMBASE, PubMed/MEDLINE, and the Cochrane CENTRAL databases from January 2000 to July 30, 2024. The search strategy utilized MeSH terms and relevant keywords, including “pregnancy,” “obstetrics,” “pregnant,” “acute kidney injury,” “acute renal injury,” “acute renal insufficiency,” “acute renal failure,” and “India.” A detailed search strategy is provided in Supplementary Annexure 1.

Article Selection

The selection process for articles is illustrated in the PRISMA flow chart (Fig. 1). After removing duplicate records, the titles and abstracts were independently reviewed by two reviewers (PM and VB) to assess eligibility. Full-text articles were screened for inclusion, with discrepancies resolved through consensus with a third author (SP). For studies with multiple publications, the most comprehensive or latest dataset was selected. Articles deemed unsuitable based on title and/or abstract consensus were excluded. Full-text articles underwent independent screening by two authors (PD and KM), with mutual agreement required for inclusion. Disagreements were addressed by consulting a third author. Data extraction was performed by four authors using a pre-designed form, and verification was conducted by two additional independent authors.

Data Extraction

Data extracted from each included article encompassed the following: Author, year of the study, site of the study in India, the total number of included patients, number of patients with PRAKI, the definition criteria of PRAKI, information about parity and timing of AKI occurrence in correspondence to the stage of pregnancy. The etiologies of PR-AKI were recorded in detail.

Outcomes

Pregnancy outcomes are categorized into maternal and fetal outcomes. Maternal outcomes included maternal survival and the need for intensive care unit (ICU) admission. Fetal outcomes included premature delivery and fetal mortality. Kidney outcomes included the need for dialysis, renal recovery, and non-recovery (progression to CKD or remaining dialysis-dependent). Information about renal biopsies was also included in provided in the study.

Quality Assessment

The quality of observational studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. (9) A comprehensive evaluation of each study is provided in the online Supplementary Annexure 2, Table 1, detailing strengths and limitations identified through these quality appraisal methods. This assessment was conducted independently by two reviewers (PD and SP), with discrepancies resolved through discussion. The certainty of evidence for each outcome was determined using the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) methodology.

Table 1

Baseline characteristics of the included studies AKI: Acute kidney injury, PRAKI: Pregnancy-related acute kidney injury,
Sl, number	First author	Year of publication	Study design	Location in India	Patients number (n)	Incidence of PRAKI	Inclusion criterion	AKI Criterion	Mean Age	Gravida	Timing of AKI
1	Goplani KR et al, (10)	2008	Prospective study	Gujrat	70	9.06%	Urine output < 400ml/day and azotemia serum creatinine > 2mg/dl	Not defined	25.6yrs	Primigravida: 22(31.4%) Multigravida: 48(68.57%) multi	Early pregnancy :14(20%) 5(7.14%) late and peupeural : 51(72.85%)
2	Najar MS et al, (11)	2008	Prospective observational	Kashmir	40	7.02%	Oliguria(urine output < 400 ml/day) or anuria with serum creatinine > 1.5 mg/dl	Not defined	28.94 ± 5.93	12 (30%)- primigravida 28 (70%)- multigravida	15 (75%)- first trimester 5 (25%)- second trimester
3	Arora N et al, (12)	2010	Prospective, Observational	West Bengal	57	6.5% of all AKI patients requiring dialysis)	sudden oliguria (urine output less than 300 mL over 24 hours), or anuria with a sudden increase in serum creatinine to more than 1.5 mg/dL or an increase in serum creatinine of more than 0.5 mg/dL per day from baseline	RIFLE	25.8 ± 4.5	primigravida − 26(45.6%) Gravida 2–9 (15.8%) Gravida ≥ 3–22 (38.6%)	11 (19.3%) cases in the first half of pregnancy (< 20 weeks of gestation) 6 (10.5%) cases in the second half of pregnancy 40 (70.2%) during puerperium
4	Sivakumar V et al, (13)	2011	Retrospective	Andhra Pradesh	59	4.36%	All PRAKI cases during study period	Not defined	25.6	NR	Postpartum 43(74.57%), Third trimester 10 (16.94%), Second trimester 4(6.77%), First trimester 2(1.69%)
5	Patel ML et al (14)	2013	Prospective	Uttar Pradesh	60	11.5%	Oliguria(urine output < 300 ml/day) or anuria with serum creatinine > 1.5 mg/dl or increase in serum creatinine > 0.5mg/dl per day from the baseline	NR	28(median age)	Primigravida 32 (53.4%)- Multiparous : 28 (46.7%)-	32 (53.3%)- early part 28 (46.7%)- later half of pregnancy and puerperium
6	Pahwa N et al, (15)	2014.	Retrospective	Madhyapradesh	27	3.59%	All the post-partum patients with AKI	RIFLE	26.7 ± 4.2	NR	Only postpartum AKI
7	Godara SM et al, (16)	2010	Prospective	Gujarat	57	9.82%	Oliguria (urine output < 400 ml/d)and/or mounting azotemia( serum creatinine > 2 mg/dL)	NR	26.4 ± 5.1	32 (56.14%) - multi- gravida 25 (43.86%) -primigravida	- Early pregnancy 10 patients (17.54%) Late pregnancy : 13 patients (22.80%) Post partum: 34; 59.64%)
8	Krishna A et al, (17)	2015	Retrospective	Uttar pradesh	98 (only dialysis requiring patient including)	3.39%	PRAKI cases requiring dialysis	-	28 ± 5	primigravida − 20(20.4%) Multi gravida 78(79.60%)	Is trimester − 15(15.3%), IInd trimester − 28(28.57%),IIIrd trimester − 55(56.12%)
9	Gopalakrishnan N et al, (18)	2015	Prospective, Observational	Chennai	130	7.8%	Increase in serum creatinine about 1.5 times from the baseline or when the urine output decreased to less than 400 mL for more than 6 hour or both	KDIGO	25.4 ± 4.7	62(47.69%) Multigravida	Is trimester – 5 (4%) IInd trimester − 11 (9%) IIIrd trimester − 24(19%) Post partum- 88(68%)
10	Gullipali et al, (19)	2015	Prospective observational	Vishakhapatnam	48	10.5%	Postpartum AKI cases	AKIN criterion	24.75 ± 4.31 years	Primigravida39 (79.16%), multigravida : 12 (20.83) %	Postpartum AKI: 100%
11	Eswarappa et al, (20)	2016	Retrospective, observational	Karnataka	99	NR	Postpartum AKI cases	RIFLE criteria	23	Primigravida: 52% Multigravida: 48%	Postpartum AKI: 100%
12	Mishra V et al, (21)	2016	Prospective observational	Gujrat	52	9.12%	Oliguria(urine output < 400 ml/day) and azotemia (serum creatinine > 2mg/dl)	NR	26.2	Primigravida 23 (44.23%)- Multigravida : 29 (55.77%)-	Early pregnancy : 3 (5.76%) Late pregnancy 49 (94.23%)-
13	Prakash J et al, (22)	2016	Retrospective	Pradesh	259	8.35% (of all AKI)	(1) Serum creatinine > 1 mg/dl, (2) oOiguria/anuria > 12 h duration, and (3) Need for dialysis (Any 1 out of 3)	None	29.8 years	NR	Early pregnancy (1st and second trimester):152 (58.68%) Late pregnancy (3rd trimester + Post partum): 107 (41.31%
14	Prakash J et al, (23)	2017	Observational, prospective	Uttar pradesh	132	(2.78%) [132 out of 4741 pregnant woman – 2.78% had AKI]	(1) sudden elevation of serum creatinine ≥ 1 mg/dl; (2) oligoanuria for > 12 h; and (3) need for dialysis.	NR	26.8 ± 4.8	Primigravida 56 (42.4%) Multigravida 76 (57.8%)	Ist trimester − 8 (6.1%) IInd trimester − 3 (1.5.%) IIIrd trimester: 88 (66.6%) Post partam-33 (25%)
15	Mir M et al, (24)	2017	Retrospective	Srinagar	28	4.27% Of all AKI	All PRAKI cases during study period	KDIGO	26.10 ± 4.3	Multi gravida 34 (75%) Primi-gravida : 12 (43%)	Only post partum AKI patients were included.
16	Tanwar et al, (25)	2018	Prospective, observational	Rajasthan	60	68 (12.8%) had postpartum AKI.	Postpartum AKI requiring dialysis delivery	Standard indications for dialysis	26.5	Primipara: 25 (41.7%) Multi gravida: 35 (58.3%)	Postpartum (100%)
17	Saini et al, (26)	2020	Prospective, observational	Kolkata, West Bengal	69	15% incidence of dialysis requiring PRAKI of all dialysis requiring AKI of the institute, one out of 470 pregnant women	All PRAKI cases during study period	KDIGO criteria	23.64	Primigravida: 31 (46%), Multigravida:38 (54%)	First trimester 4 (4.9%), Second trimester 5 (6.17%), Third trimester and postpartum 72 (88.88%)
18	Chowdhary PK, (27)	2021	Retrospective ,observational	Raipur	107	3.26% (Only post partum AKI included)	All postpartum AKI.	KDIGO AKI criteria	27.3 ± 4.77 years	Primipara-58 (54.2%) Multipara- 49 (45.8%)	All postpartum AKI
19	Banerjee A et al, (28)	2020	Prospective study,	Uttar Pradesh	36	NR	• 1) Two rimes increase in serum creatinine from baseline. • 2) Urine output < 0.6 mL/kg in the last12 hrs; or • 3)Urea > twofold from the baseline	RIFLE criteria.	Patients divided in two froups Groupt 1 : early RRT : 13 (27.34%) Group two : 23 (28.96%)	NR	NR
20	Sahay M et al, (29)	2022	Retrospective, observational	Hyderabad	395	8.1%	• All PRAKI cases during study period	KDIGO	27 ± 3 years	Multigravida- 231 (58.6%)	Postpartam- 288 (72.9%) Antepartam – 107 (27.08%) Before or within 7 days of delivery- 207(52.4%) Between 7–14 days of delivery- 129 (32.6%) ≥ 14 days: 57 (14.4%)
21	Sachan R et al, (30)	2022	Prospective observational	Uttar pradesh	150	Out of 14750 obstetrics pt, 150 (1%), PRAKI	• All PRAKI cases during study period	KDIGO	20–35 years	-	-
22	Yadav S et al, (31)	2022	Prospective, Observational	Haryana	51	NR	• Increase in serum creatinine by ≥ 26.5 µmol/L within 48 h, increase to more than 1.5 times baseline, or reduced urine volume < 0.5 mL/kg/h for six hours.	RIFLE	25.9	Primigravida: 21(41.2%) Multigravida 30(58.8%)	Third trimester- 21 (50.9%)
23	Sandilya S, (32)	2023	Prospective observational	New Delhi	50	NR	• All PRAKI cases during study period	KDIGO	25.18 ± 3.8	NR	Postpartum– 12 (24%)
24	Kharkongor D et al, (33)	2023	Prospective observational	Uttar pradesh	110	1.08%	• All PRAKI cases during study period	KDIGO	27.95 ± 4.85	Primigravida 34 (30.9%), Multiparous 76(69.1%)	NR
25	Saxena D et al, (34)	2024	Prospective observational	Rajasthan	62	11.8%	• PRAKI patients requiring dialysis	KDIGO	28 ± 3	Primigravida 24 (38.7%), Multigravida: 38 (61.3%)	Postpartum: 53 (85.5%)

Data synthesis

The ReviewManager 5.4 (RevMan) Meta-Analysis software, was used for all statistical analyses. Proportions and percentages were calculated for each outcome in the context of PRAKI cases, using the total number of PRAKI patients as the denominator. Trends in maternal and kidney outcomes were assessed across studies, focusing on variations in PRAKI definitions and geographic differences in outcomes. Additionally, narrative synthesis was employed to describe the range of kidney outcomes. No meta-analysis was performed due to heterogeneity in study designs, lack of RCTs and outcome reporting across studies.

Study selection

The initial search yielded 3608 articles, after removing duplicates (n = 32), 3576 studies underwent title and abstract screening. The full texts of 500 articles were retrieved for eligibility assessment, and 474 articles were excluded for the following reasons: outside India (n = 198), not reporting kidney outcome (n = 36), case reports (n = 110), review articles (n = 88), a systematic review from another continent (n = 1), a systematic review on cardiovascular outcomes and aetiology (n = 2), study reporting outcomes only in pre-eclampsia cases (n = 1) and conference abstracts (n = 40). Finally, a total of 2306 patients across 25 studies were included in the final analysis. (10–34), See Fig. 1 for PRISMA flowchart.

Baseline characteristics

The incidence of PRAKI in Indian studies has varied, ranging from 1.08–12% of AKI cases reported by different centres. Jaiprakash et al. and Sachan et al. reported AKI incidence rates of 2.73% and 1%, respectively, among all pregnancies during their study periods (23, 30). The baseline characteristics of the included studies are provided in Table 1.

The patient population in the included studies varied from 27 to 395 individuals, with the majority being conducted in government hospitals. However, one study was conducted at a private tertiary care centre. (16) All the studies were single-centre and 8 out of 25 studies were retrospective in design. (13, 16, 17, 20, 22, 24, 27, 29). The third trimester or postpartum period was identified as the most common phase for the presentation of PRAKI with up to 80% of cases occurring during this time. Notably, Najar et al. reported a significant number of early-trimester AKI cases (75%). (11) There was a general predominance of multigravida patients in the reviewed studies. The criteria for defining AKI were not uniform across the studies; only 9 studies applied the KDIGO AKI criteria for staging. (18, 24, 26, 27, 29, 30, 32, 33, 34). In contrast, other studies defined AKI based on oliguria or an increase in serum creatinine levels. Additionally, six studies focused exclusively on postpartum AKI cases. (16, 19, 20, 24, 25, 27)

Etiology of PRAKI

Sepsis was found to be the most frequent cause of PRAKI, ranging from 13.9–78.8% across different cohorts. (See Table 2) Puerperal sepsis was commonly reported, constituting the primary cause of sepsis in many studies, while post-abortal sepsis also contributed significantly in some. (10, 11, 16, 17 ), Najar et al. reported septic abortion as the most common cause accounting for 20 (50%) of the women with PRAKI, 15 (75%) of which occurred in the first trimester and five (25%) in the second trimester. Of 20 patients with septic abortion, 18 (90%) were from rural areas and their abortions had been conducted by untrained midwives. (11) Pre-eclampsia and eclampsia, another significant contributor to PRAKI, appeared frequently in multiple studies, with incidences ranging from 14–46.9%. Gopalakrishnan et al. reported a 21% incidence of pre-eclampsia/eclampsia, (18) while Prakash et al. found it in 46.9% of cases. (23) In addition, HELLP syndrome was a contributing factor in certain cases, with incidences as high as 44.45% reported by Kharkongor et al. (33) Obstetric hemorrhages such as antepartum haemorrhage (APH) and postpartum haemorrhage (PPH) were also prevalent in many of the studies. Krishna et al. found that 23.4% of patients experienced APH and PPH, (17) while Sahay et al. reported a combined incidence of 44.5%. (29) Other studies, such as those by Sandilya et al. and Kharkongor et al., reported significant occurrences of hemorrhage-related complications, which were often associated with sepsis or pre-eclampsia. (32–33) Glomerular diseases contributed to 0.7 to 5.8% of PRAKI cases. The most common aetiology was lupus nephritis. Several other etiologies were noted across the reviewed studies, including malaria, snake bite, acute gastroenteritis, hemolytic uremic syndrome (HUS), and acute fatty liver of pregnancy (AFLP). Out of total of 2306 case of PRAKI, AFLP was only due to 18 cases. Only 3 cases were contributed by obstructive etiology.

Table 2

Etiologies of Pregnancy associated acute Kidney Injury
Sl, number	First author	Sepsis (n%)	Sepsis Etiology	APH (n%)	Pre-eclampsia/Eclampsia (n%)	PPH (n%)	Glomerular Disease (n%)	HELLP (n%)	AFLP (n%)	Others with Etiology
1	Goplani KR et al, (10)	57 (71%)	Puerperal sepsis − 43 and post abortal-14	10 (14.28%)	20 (28.57%) (includes HELLP)	17 (24.28%)	NR	NR	NR	Malaria (3) (4.28%)
2	Najar MS et al, (11)	20 (50%)	Abortion, Acute pyelonephritis-2 (5%),	6 (15%)	6 (15%)	2 (5%)	NR	NR	NR	AGE-3 (7.5%)
3	Arora N et al, (12)	19 (33.3%)	Puerperal sepsis (100%)	-	PE/other hypertensive disorder-7 (12.3%), Eclampsia-8 (14.0%)	16 (28.1)	NR	NR	NR	Snake bite-2 (3.5%), Perioperative hypotension-1 (1.7%), HUS-1 (1.7%), Unknown-3 (5.3%)
4	Sivakumar V et al, (13)	28 (47.41%)	Puerperal sepsis: 28 (47.41%)	5 (8.47%)	17 (30.50%)	6 (10.16%)	NR	NR	NR	Miscellaneous (18.64%)
5	Patel ML et al (14)	25 (41.7%)	Post partum sepsis	4 (6.66%)	20 (33.3%)	4 (6.66%)	-	1 (1.7%)	-	Abortion-5 (8.3%), DIC-1 (1.7%)
6	Pahwa N et al, (15)	19 (70.3%)	Puerperal sepsis: 9 (29.7%) UTI: 5 (18.5%)	2 (10%)	2 (10%)	1 (6%)	NR	2 (8.4%)	NA	HUS-2 (9%)
7	Godara SM et al, (16)	N = 44 (78.8%)	Puerperal sepsis: 44 (63.1%), post-abortion sepsis: (4) 15.7%	7 (14%)	14 (33.33%)	2 (8.7%)	FSGS − 1(1.75%), MPGN-1 (1.75%)	NR	NR	Malaria 3(5.2%),
8	Krishna A et al, (17)	55 (56.1%)	Post abortal	PPH + APH-23 (23.4%)	14 (14.2%)	NR	NR	4 (4.08%)	HUS-2 (2.04%)	NR
9	Gopalakrishnan N et al, (18)	51 (39%)	Septic abortion-4 (7.84%), Puerperal sepsis − 47 (92.15%)	13 (10%)	27 (21%)	3 (2%)	4 (3%)	5 (3.84%)	NR	Acute Diarrhea-13 (10%), TMA-11 (9%), Others-3 (2.30%)
10	Gullipali et al, (19)	16 (33.33%)	Puerperal sepsis in all cases of sepsis	2(4.16%)	12(25%)	6 (12.5%),	5 (10.41%)	12(25%) with pre eclampsia	NR	Complicated malaria: 3(6.25%)
11	Eswarappa et al, (20)	74 (75%)	Puerperal sepsis: 60.6%(n = 61) UTI: 6 (6%) Septic thrombophlebiitis 1 (1%) Necrotizing fascitis 1 (1%) Mucormycosis 1 (1%)	NR	NR	12% (n = 14)	LN-1 (1%),	n = 10 (8%) along with preeclampsia	None	HUS-1 (1%),Transfusion reaction − 1(1%), Isolated postpartum PIH-1 (1%) H1N1: 1 (1%)
12	Mishra V et al, (21)	17 (32.6%)	Post abortal-3 (5.77%) Peurperal-8 (15.38%), Combined hemorrhage and sepsis : 9 (17.30%).	9 (17.30%)	PE-31 (59.6%), Eclampsia-4 (7.69%)	11 (21.15%)	-	1 (1.92%)	1 (1.92%)	Malaria, IUD with sepsis
13	Prakash J et al, (22)	39 (15%)	Puerperal sepsis: 39 (15%)	(APH + PPH) 25 (9.65%)	PE + HELLP: 41 (15.8%)	NR	LN : 2 (0.07%)	NR	1 (0.06%)	152 (58.68%) Post abortal, HUS : 1 (0.06%)
14	Prakash J et al, (23)	42 (31.8%)	Puerperal sepsis-34 (25.8%), Post abortal sepsis-8 (6.1)	11 (8.3%)	62 (46.9%)	28 (21.2%)	1 (0.75%)-LN	9 (6.8%)	5 (3.8%)	Fulminant hepatitis-4 (3.03%), Acute gastroentritis-3 (2.27%), UTI-2 (1.5%), Complicated malaria-1 (0.75%)
15	Mir M et al, (24)	11 (39.28%)	Puerperal sepsis : 11 (39.28%) Acute pyelonephritis-3 (11%)	NR	4 (14%)	7 (25%)	ANCA-1 (4%),	NR	NR	HUS-1 (4%)
16	Tanwar et al, (25)	31(61.6%)	Puerperal sepsis: 31(61.6%)	14 (23.3%)	21 (35%)	7 (11.7%)	NR	3 (5%)	4( 6.7% )	Tropical infections, malaria- 02 (5%), TMA − 2 (3.3%), Hemorrhage in early pregnancy (8.7%) Dengue hemorrhagic fever, N = 1
17	Saini et al, (26)	42 (49.4%)	Puerperal sepsis: 41 (49%)	NR	13 (12.3%)	12 (16%))	NR	3 (4.9%)	2 (2.4%)	Malaria (1.2%), Unexplained (1.2%) P-aHUS : 14 (17.28% )
18	Chowdhary PK, (27)	35 (32.71%)	Puerperal sepsis, RPOC-6 (17.14%), UTI-22 (62.85%), Pneumonia-6 (17.14%), Abdominal wound-5 (14.28%), Episiotomy wound-3 (8.57%)	NR	8 (7.47%)	4 (3.73%)	2 (1.86%)	NR	1 (0.93%)	HUS, N = 1
19	Banerjee A et al, (28)	5 (13.9%)	Bacterial sepsis : 5 (13.39) Viral sepsis: 3 (3.33%)	NR	13 (36.11%)	Total 4 (11.11%) hemorrhage cases	None	1 (2.72%)	2 (5.56%)	Hyperemesis gravidarum: 2 (5.56%), Malaria: 4 (11%), Dengue :1 (2.72%), Snake bite: 1 (2.72%)
20	Sahay M et al, (29)	132 (33.41%)	NR	31 (8%)	176 (44.5%)	46 (12%)	11 (2.7%)	GN 11 (10.6%)	NR	9 (8.7%)-HUS Obstruction: n = 2
21	Sachan R et al, (30)	68 (45.3%)	Puerperal sepsis, n = 64 (42.6) Septic abortion, 4 (2.6%)	15 (10%)	HDP: 72 (48%) PE-30 (20%) / EC-42 (28%)	39 (26%)	NR	NR	NR	AGE : n = 2, Liver dysfunction n = 11, Heart diseases, n = 2 Caogulopathy, n = 25
22	Yadav S et al, (31)	21(18.1%)	Puerperal Sepsis	-	PE- 14 (39%) Eclampsia – 8(13%)	NR	NR	6 (16.6%)	NR	AGE − 01 (3%)
23	Sandilya S, (32)	12 (24%)	Puerperal sepsis: 12 (24%) Pyelonephritis : 2 (4%)	Abruption :7(14%)	14 (28%),	10 (20%)	NR	NR	NR	TMA : 1 (2%)
24	Kharkongor D et al, (32)	31 (28.18%)	Puerperal + postabortal + sepsis: 31 (28.18%)	APH + PPH + post abortal: 39 (35.45%)	PE/Eclampsia/HELLP: 49 (44.45%)	APH + PPH 49 (44.54%)	NR	PE/Eclampsia/HELLP: 49 (44.45%)	12 (10.91%)	Others: 3 (2.72)
25	Saxena D et al, (34)	20 (29.4%)	NR	1 (1.4%)	9 (13.2%)	18 (26.4%)	4 (5.8%)	2 (2.9%)	NR	Obstructive uropathy, n = 1 (1.4%)
AFLP: Acute fatty liver of pregnancy, HUS: hemolytic uremic syndrome, APH: Antepartum haemorrhage, PPH: Antepartum haemorrhage, HELLP: Hemolysis, Elevated Liver enzymes and Low Platelets, RPOCs: retained products of conception, PE : Pre-eclampsia, TMA: Thrombotic microangiopathy, AGE: Acute Gastroenteritis, UTI: Urinary tract infection, HDP: Hypertensive disorders of pregnancy

Renal outcome

Renal outcomes in PRAKI varied considerably across studies, with a significant proportion of patients requiring renal replacement therapy (RRT) up to 85%, including hemodialysis (HD) and peritoneal dialysis (PD), as well as long-term impacts such as chronic kidney disease (CKD) and dialysis dependency. See Table 3. In the majority of the studies, hemodialysis modality was used, in only 3 studies use of PD was reported. (20, 24, 25). For instance, in the cohort by Goplani et al., 97.14% of patients underwent HD, and 85.9% achieved full recovery, though 12.85% progressed to CKD, and 14.28% became dialysis dependent. (10) Similarly, Najar et al. found that 40% of their patients required dialysis, with 72.5% achieving full recovery, while only 5% developed CKD. (11)

Table 3

Renal outcomes HD: Hemodialysis, ATN: acute tubular necrosis, ATIN: Acute tubulointerstitial nephritis, ACN: Acute cortical necrosis, TMA: Thrombotic microangiopathy, CRRT: Continuous Renal Replacement Therapy, FSGS: focal and segmental glomerulosclerosis, MPGN: membranoproliferative glomerulonephritis, MGN: membranous glomerulonephritis, PD: Peritoneal dialysis, LN: Lupus nephritis, GN: Glomerulonephritis, CVVHDF: Continuous venovenous hemodiafiltration,
Sl, number	First author	Renal biopsy	RRT modality	Dialysis requirement	Full revovery	CKD development	Dialysis dependant
1	Goplani KR et al, (10)	Performed in 11 (N = 11)patients ACN: 10 Glomerular endotheliosis-1(associated with preeclampsia)	89, (97.14)% -HD 8 (8.6%) patients received PD initially and later shifted to HD.	49 (85.9%)	38 (54.28%)	9 (12.85%)	10(14.28%)
2	Najar MS et al, (11)	NR	HD: 13 (32.5%) PD: 6(15%) and both modalities to 5 (12.5%)	24(40%)	29 (72.5%)	2 (5%)	1 (2.5%)
3	Arora N et al, (12)	Renal Biopsy in patients ATN: 2, ACN: 3, subacute interstitial nephritis :1 Inconclusive 1	100% HD	49 (6.9%)	24 (50)	5 (8)	3(5.2)
4	Sivakumar V et al, (13)	NR	HD 29 (49.15%), CVVHD 4 (6.77%), PD 3 (3.38%)	35 (59.3%)	31 (54.23%)	6 (10.16%)	NR
5	Patel ML et al (14)	NR	Hemodialysis- 23 (38.33%)	23(38.33%)	45 (75%)	1 (1.7%)	5 (8.3%)
6	Pahwa N et al, (15)	N = 11 (18.5%) ACN 5,	All HD	25 (92%)	11(40. 7%)	6(22.2%)	2(7.4%)
7	Godara SM et al, (16)	N = 21 (36.84%) ACN : n = 13 (61.9%), ATN n = 4, Glomerular disease (n = 3,) FSGS-1. MPGN-1 MGN-1 ATIN-1	HD: 50 (87.7%), PD :3 (5.2%)	50 (87.7%)	50 (52.64%)	12 (21.05%)	15 (26.31%)
8	Krishna A et al, (17)	N = 16 ACN- 8 ACN(patchy) + TMA − 6 ATN − 2	HD: 98 (100%)	24 (24.49%)1 session HD 74 (75.5%)-multiple sessions	53 (54.28%)	13 (12.85%)	14 (14.28%)
9	Gopalakrishnan N et al, (18)	N = 46 (35.3%), ACN: 16 (34.7%), TMA: 11 (23.9%), ATN: 9 (19.5), ATIN: 1 Glomerular disease- 9 (Lupus nephritis 4 IgA nephropathy 1 Diffuse mesangial proliferation 1 Focal segmental glomerulosclerosis 1 Pauci-immune necrotising GN 1 Infection-related GN- 1)	All HD	96 (74%)	73 (56%)	46 (35%)	1(7.69%)
10	Gullipali et al, (19)	N = 15 (31.2%) ACN: 6 (12.5) LN : 4 (8.3) TMA: 3 (6.24%) FSGS : 1 (2.08%) ATN: 1 (2.08%)	HD in all patients	23(47%)	38 (79.4%)	2 (4.1%)	4(8.3%)
11	Eswarappa et al, (20)	NR	HD: 29 (29%), PD :6(6%), CRRT : 4 (4%)	39 (39%)	70 (70%)	5 (5%)	3 (3%)
12	Mishra V et al, (21)	N = 10 ACN- 8 ATN- 2	All HD	43 (84.62%)	29 (55.76%)	19 (50%)	4(7.69%)
13	Prakash J et al, (22)	N = 18 Diffuse ACN 8 Patchy ACN 7 Glomerular disease-2, both LN Changes of CKD- 1	All HD	223 (86.1%)	199 (76.83%)	28 /259 (10.8%)	7 (2.7%)
14	Prakash J et al, (23)	N = 4 ACN:N = 3, LN: N = 1	All HD	62 (47%)	118 (89.4%)	8(6.06%)	6 (4.6%)
15	Mir M et al, (24)	N = 9 (14.7) ACN n = 4(44.44). ATN: n = 3 (33.33) Glomerular disease : 1 (pauci-immune GN)(11.11), TMA: 1 (11.11)	9 (33%) HD and 4 (14%)-PD	13(46%)	15(54%)	6(21%)	4(14%)
16	Tanwar et al, (25)	N = 11 (18.3%) ACN: 6, ATN: 2 TMA: 2 Inconclusive: 1	HD :54 (90%), PD : 25(41.7%),	100%	NR	31 (51.3%)	2(5.4%)
17	Saini et al, (26)	N-24(30%) TMA: 13 (54%) ACN:4 (17) ATN: 6(25) Diffuse Glomeruloscleorsis: 1 (4%)	HD: 68 (84%)	68 (84%)	27 (39%)	23 (33%)	11 (16%)
18	Chowdhary PK, (27)	N = 7(6.54%) patients ATN:n = 3 ACN: N = 3, and TMA: n = 1	All HD	73 (68.22%)	75 (88.2%)	6(7.05%)	4(4.7%)
19	Banerjee A et al, (28)	NR	All HD	Only dialysis patients included	NR	NR	Total n = 3 (8.3%) Early RRT group-2(15.38%), Standard RRT group-1(4.35%)
20	Sahay M et al, (29)	N = 103 Patchy cortical necrosis 25 (22.3%), Diffuse ACN 23 (20.3%), ATN 20 (19.4%), AIN 10 (9.7%), TMA 9 (8.7%), GN 11 (10.6%), IgA n = 4, MPGN,n = 2, FSGS n = 2, LN n = 3, endotheliosis, n = 2	All HD	290(73.6%)	285 (76%)	59 (15.7%)	31 (8.3%)
21	Sachan R et al, (30)	NR	HD	98(65.33%)	41(27.3%)	46(31.3%)	5(3.39%)
22	Yadav S et al, (31)	NR	NR	14 (27.5%)	33 (64.7%)	6 (12%)	NR
23	Sandilya S, (32)	NR	HD	23 (46%)	40 (80%)	10 (20%)	NR
24	Kharkongor D et al, (32)	NR	HD	29 (26.4%)	45(40.9%)	25 (22.7%)	10 (9.1%)
25	Saxena D et al, (34)	N = 33 Diffuse ACN-14 Patchy ACN − 6 ATN − 9 Glomerular disease − 4	HD	62 (72.1)	21 (38.2%)	15 (30%)	16 (32%)

Outcomes also varied significantly regarding CKD development and dialysis dependency. For example, Prakash et al. found that 76.83% of patients fully recovered, though 10.8% progressed to CKD. (22) Gopalakrishnan et al. identified 35% of patients developing CKD, with 7.69% becoming dialysis dependent. (18) Mir et al. noted a CKD development rate of 21%, (24) while Pahwa et al. reported a 22.2% progression to CKD among their patients. (16) Tanwar et al. found that 51.3% of patients progressed to CKD. Saxena D et al also reported a very high rate of CKD development in 15 (30%), and 16 (32%) remaining dialysis dependant. (35)

In terms of non-recovery of renal function, patients who did not recover renal function by six weeks exhibited a substantially elevated risk of prolonged non-recovery, with an RR of 24.7 (95% CI: 3.4–179.5). (17) Saini et al., in their multivariate analysis, identified TMA as a significant predictor of non-recovery, with an odds ratio (OR) of 14.00 (95% CI: 1.13–172.58, P = 0.039). Other important but non-significant predictors included obstetric haemorrhage (OR: 7.50, 95% CI: 0.62–90.61, P = 0.11) and sepsis (OR: 4.28, 95% CI: 0.44–41.35, P = 0.20). (26) Sahay et al. further highlighted that clinical variables such as anuria, sepsis, TMA, and findings of cortical necrosis on renal biopsy were crucial predictors of non-recovery of renal function in PRAKI patients. (20)

Renal biopsy data

Renal biopsy was reported in 346 (15%) of patients. See Fig. 2. The most common finding was ACN in 172 (49.71%) followed by acute tubular necrosis in 63 (18.2%), TMA in 47 (13.5%), GN in 36 (10.4%) and ATIN in 13 (3.75%). The most common GN was LN (N = 14), followed by IGAN (N = 5), FSGS (N = 5), MPGN (N = 3), membranous nephropathy (N = 1), ANCA vasculitis (N = 2) and infections related GN (N = 1). Changes of endotheliosis were reported in 3 patients.

Fetomaternal outcome

The fetomaternal outcomes in PRAKI in India demonstrate significant variability across 25 different studies. See Table 4. Maternal mortality ranged from 2.5–34%. Larger studies, such as Sachan et al reported a maternal mortality rate of 34% (30) Patel et al. observed a 15% maternal mortality rate, (14) with Pahwa et al. reporting 18.51%. (16) Several other studies also reflected similar mortality rates. Perinatal outcomes were also significantly impacted. For example, Krishna et al. reported a perinatal mortality rate of 26.19%, (17) Mishra et al. observed fetal mortality as high as 67.3%. (21) The adverse fetal outcomes reported by Gopalakrishnan et al., which included intrauterine death (IUD) and stillbirths, were 54%. (18) Pre-term delivery was reported in several studies, with rates ranging from 13.9–58%. For example, Sandilya S and Eswarappa reported very high rates of premature deliveries with rates of 40%, and 58% respectively.(32, 20). Krishna et al. (17) reported several significant risk factors associated with increased mortality in patients with PRAKI. The risk of mortality was markedly higher in individuals with oliguria, sepsis, central nervous system involvement, hepatic dysfunction, and low platelet counts. Additionally, patients requiring multiple dialysis sessions had a significantly higher risk, with a relative risk (RR) of 2.96 (95% CI: 1.75–4.99, P = 0.001).

Table 4

Maternal and fetal outcomes
Sl, number	First author	Maternal mortality (N%)	Requirement of ICU (N%)	Perinatal mortality (N%)	IUD (N%)	Pre-mature deliveries, (N%)
1	Goplani KR et al, (10)	13 (18.57%)	NR	NR	NR	NR
2	Najar MS et al, (11)	8 (20%)	NR	NR	NR	NR
3	Arora N et al, (12)	16 (28.1%)	NR	NR	NR	NR
4	Sivakumar V et al, (13)	14 (23.72%)	NR	NR	NR	NR
5	Patel ML et al (14)	9(15%)	NR	NR	NR	25 (41.7%)
6	Pahwa N et al, (15)	5 (18.51%)	NR	NR	NR	NR
7	Godara SM et al, (16)	9 (15.78%)	NR	28 (49.12%)	3 (5%)
8	Krishna A et al, (17)	18 (18.36%)	13 (13.8%)	25 (26.19%)	NR	NR
9	Gopalakrishnan N et al, (18)	10 (7.69%)	NR	Adverse fetal outcome (IUD + stillbirth) 70 (54%)	29 (23%)	NR
10	Gullipali et al, (19)	4 (8.3%)		NR	7 (14.7%)	11 (22.9%)
11	Eswarappa et al, (20)	18 (19%)	99 (100%)	14 (22%)	NR	NR
12	Mishra V et al, (21)	17(32.69%)	15 (28.85%)	Fetal mortality − 67.3%	17 (32.69%)	NR
13	Prakash J et al, (22)	25 (9.60%)	NA	117 (45.17%)	NR	NR
14	Prakash J et al, (23)	8 (6.1%)	NR	30 (23%)	23 (17.5%)	54 (40.9%)
15	Mir M et al, (24)	3 (11%)	NR	3 (11%)	2 (7.15%)	NR
16	Tanwar et al, (25)	17 (28.3%)	17 (31.7%)	NR	14 (23.3%)	NR
17	Saini et al, (26)	20 (25%)	NR	19 (23.5%)	NR	NR
18	Chowdhary PK, (27)	22 (20.56%)	NR	15 (14.01%)	NR	NR
19	Banerjee A et al, (28)	1 (2.7%)	36 (all in ICU)	Total n = 14 (38.8%), Early RRT: 2 (14.29%), Standard : 12 (85.71%)	NR	18 (50%) , Early 8 (44.44%), Standard 10 (55.56%)
20	Sahay M et al, (29)	20 (5%)	NR	30 (7.5%)	42 (10.6%)	45 (13.9%)
21	Sachan R et al, (30)	51 (34%)	149 (96.1%)	56 (38.4%) (IUD + Still births)	56 (38.4%)	34 (23.3%)
22	Yadav S et al, (31)	14 (23.5%)	18 (33.3%)	19 (37.3%)	20 (39.2%)	8 (15.7%)
23	Sandilya S, (32)	7 (14%)	50 (100%)	6 (16%)	12 (24%)	20 (40%)
24	Kharkongor D et al, (32)	22 (20%)	NR	NR	NR	NR
25	Saxena D et al, (34)	9 (14.5%)	NR	NR	16 (25.8%)	12 (19.4%)
IUD: Intrauterine deaths, ICU: Intensive care unit, RRT: Renal replacement therapy, NR: Not reported/not clear

Figure 5 shows the visual graphical summary of the findings of the analysis.

The present review of 25 Indian studies, comprising over 2306 patients, highlights significant findings concerning PRAKI with incidence varying from 1 to 12% at different centres. The third trimester and postpartum period were identified as the most common times for the onset of PRAKI, accounting for up to 80% of cases. However, in a study by Najar et al., early trimester AKI constituted a notable 75% of cases, indicating that early pregnancy is also a vulnerable period for AKI development. The majority of these cases were due to septic abortion. (11) A striking 90% of these cases occurred in rural areas, where abortions were often performed by untrained midwives.

Sepsis emerged as the most frequent cause of PRAKI, with an incidence ranging from 13.9–78.8% across various cohorts. Puerperal sepsis was often cited as the leading cause, though post-abortal sepsis also contributed significantly, particularly in rural areas. The decline in septic abortions over recent years is likely due to improved policies and healthcare access, yet a significant proportion of sepsis cases were still associated with unsafe abortions carried out by traditional birth attendants. Pre-eclampsia and eclampsia were other significant contributors to PRAKI, with reported incidences ranging from 14–46.9%. Obstetric hemorrhages, were also common causes of PRAKI. While the most common causes of PRAKI—sepsis, hypertensive disorders of pregnancy (HDP), and hemorrhage—account for more than 50% of cases, less common causes such as glomerulonephritis, HELLP syndrome, AFLP and HUS were also noted. None of the studies reported thrombotic thrombocytopenic purpura (TTP) or complement-mediated disorders as causes of PRAKI nor did they provide any genetic information related to these conditions. This suggests a potential underdiagnosis of such disorders, likely due to financial constraints and limited access to advanced diagnostic tools. See Fig. 3 for common etiologies of PRAKI in developing countries. Figure 4 provides key causes of PRAKI categorized by the stage of pregnancy.

Renal outcomes varied significantly. Up to 85% of PRAKI patients required RRT. Some studies like by Mir et al., Pahwa et al and Tanwar et al reported very high rates of CKD development in 25 to 50% of PRAKI cases (24, 16, 25) Saxena D et al also reported a very high rate of CKD development in 15 (30%), and 16 (32%) remaining dialysis dependant. (34)

This highlights the need for long-term follow-up to monitor renal function and manage the progression to ESKD. Maternal outcomes were similarly concerning, with mortality rates ranging from 2.5–34%. Larger studies, such as those by Sachan et al and Patel et al, reported maternal mortality rates of 34% and 15%, respectively. (14, 30) Pre-term deliveries are common, with incidences ranging from 13.9–58%.

The incidence of PRAKI in pregnancy in India has shown a decline over the years, with older studies reporting rates as high as 12%, while more recent data, such as the 2023 study by Kharkongor et al., report an incidence of only 1.08%. (33) This reflects improvements in antenatal care and healthcare awareness among pregnant women. Despite these advances, sepsis remains the predominant cause of PRAKI in many developing regions. The shift from post-abortal sepsis as the leading cause to puerperal sepsis reflects improvements in antenatal care but also highlights the persistent risk of sepsis following childbirth.

The low socioeconomic status of the majority of patients, particularly in rural areas (most of the included centres cater to low socioeconomic groups and rural populations), remains a major barrier to adequate prenatal care and timely treatment. Some studies reported that a substantial percentage of patients had not received any antenatal care, and many deliveries were attended by untrained traditional birth attendants. For instance, Patel et al. found that 53.3% of patients had no antenatal care, with the majority delivering at home. (14) The lack of antenatal care significantly contributes to the burden of PRAKI, as early detection and management of complications such as sepsis, haemorrhage, and hypertensive disorders are critical for improving outcomes..

The high rates of CKD progression show the long-term renal damage that can follow an AKI episode during pregnancy, particularly in cases complicated by sepsis, preeclampsia, or obstetric haemorrhage. The progression to CKD is concerning not only because of its immediate health implications for women but also due to its contribution to the broader CKD burden in India. The country is already burdened with an escalating CKD epidemic, driven by factors such as diabetes, hypertension, and newly recognized hot spots for CKD of unknown etiology (CKDu). and poor access to healthcare. PRAKI, which affects women of lower socioeconomic status—often those with limited access to healthcare access adds another dimension to this epidemic. Reports indicate an age-adjusted incidence of ESKD in India as 229 per million population, more than double the previously estimated rate of 100 per million. India now has already had over 130,000 patients receiving dialysis, with the number steadily rising. (35) The findings from this review suggest that PRAKI is a critical, yet underrecognized, factor in this epidemic, contributing both to the growing number of CKD cases and to the increasing demand for RRT. The strain on healthcare resources due to PRAKI-associated CKD is likely to grow as more women survive acute episodes but remain at risk for long-term renal impairment. Without proper follow-up and management, these women may require lifelong dialysis or kidney transplantation, both of which are limited for socioeconomically challenged group.

A systematic review from African countries identified preeclampsia, obstetric haemorrhage, and sepsis as the primary causes of PRAKI with maternal mortality ranging between 0% and 34.4%. While most women required ICU admission and HD, renal recovery was achieved in 53.1–90% of cases. Perinatal mortality was also significant, ranging from 1.5–60.5%. (36)

Studies from other countries report that the prevalence of PRAKI ranges from 2–8% in hypertensive disorder cohorts and from 5–18% in preeclampsia cases. In severe cases of eclampsia that require intensive care, PRAKI incidences can reach as high as 67%. Preeclampsia complicated by PRAKI significantly increases maternal mortality rates (3%) compared to preeclampsia without PRAKI (0.5%). (3) However, in India, sepsis remains the predominant cause of AKI, although there has been a shift towards hypertensive disorders of pregnancy (HDP) and hemolytic uremic syndrome (HUS) as major causes.

One of the key strengths of our systematic analysis is the comprehensive inclusion of 25 studies from across India, involving more than 2300 patients, which provides a broad representation of the burden of PRAKI in a developing country context. This review draws attention to the significant variability in PRAKI aetiology, clinical presentation, renal biopsy findings and outcomes. By synthesizing data across diverse cohorts, our analysis emphasies the long-term impact of PRAKI on the CKD epidemic, particularly its contribution to CKD progression and dialysis dependency. Moreover, our review identifies critical gaps in PRAKI diagnosis and follow-up, highlighting the need for standardized diagnostic criteria and long-term monitoring. The focus on socioeconomic and healthcare disparities provides a valuable lens for understanding the disproportionate impact of PRAKI in low-resource settings, further strengthening the relevance of our findings to public health and policy interventions.

While this systematic review sheds light on PRAKI in India, it has limitations. The heterogeneity of the studies, single-centre analysis, and some retrospective studies limit the robustness of the findings. Furthermore, the absence of data from private sector hospitals and urban health facilities likely skews the understanding of PRAKI incidence and outcomes. The lack of meta-analysis due to study heterogeneity limits the ability to draw conclusive generalizations from the data. A major limitation of the reviewed studies was the heterogeneity in defining PRAKI. Only 9 studies used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, while others relied on less specific measures such as serum creatinine levels or oliguria or previously used AKIN/RIFFLE criterion. This inconsistency in diagnostic criteria makes cross-study comparisons challenging and may lead to underreporting or misclassification of PRAKI. The absence of uniform definitions also raises concerns about the accuracy and comparability of outcomes, highlighting the need for standardized diagnostic protocols in pregnancy-related kidney injury research. Early detection and timely interventions are crucial to reducing these fatal outcomes, but the current healthcare infrastructure and resources in many developing countries are insufficient to meet this need. The burden of PRAKI, particularly in developing countries like India, necessitates urgent attention from healthcare authorities and professionals. The management of PRAKI requires a multidisciplinary approach. Specialized obstetric nephrology clinics could provide early diagnosis and long-term management for both mothers and their infants. Public awareness campaigns, improved access to prenatal care, safer abortion services, and delivery by skilled healthcare professionals will be instrumental in reducing the incidence of PR-AKI and its related complications. Additionally, strengthening communication and referral systems in rural areas, and establishing more obstetric critical care units at tertiary centres, may reduce mortality associated with PR-AKI, particularly in resource-poor settings

Our review also highlights the critical need for community awareness programs to educate women about the importance of antenatal care, safe delivery practices, and the potential long-term consequences of PRAKI. Improved access to healthcare resources, including well-trained personnel and modern diagnostic tools, is essential to managing high-risk pregnancies effectively.

Conclusion: While the incidence of PRAKI in India has decreased due to better healthcare access and awareness, the condition continues to pose a significant risk to maternal and fetal health. CKD following an AKI episode during pregnancy poses a significant burden to the rising number of CKD patients in the health care system. Further research, particularly large multicenter studies, is needed to better understand the risk factors and outcomes of PRAKI and to improve strategies for early detection, management, and prevention.

ATN: Acute tubular necrosis
PRAKI: Pregnancy associated Acute kidney injury
ACN: Acute cortical necrosis
AKI: Acute kidney injury
CKD: Chronic kidney disease
ESKD: End-stage kidney disease
KDIGO: Kidney Disease: Improving Global Outcomes
LM: Light microscopy
AFLP: Acute fatty liver of pregnancy
HUS: hemolytic uremic syndrome
APH: Antepartum haemorrhage
PPH: Antepartum haemorrhage
HELLP: Hemolysis, Elevated Liver enzymes and Low Platelets,
RPOCs: retained products of conception,
PE : Pre-eclampsia
TMA: Thrombotic microangiopathy
HDP: Hypertensive disorders of pregnancy
HD: Haemodialysis
RRT: Renal replacement therapy
TMA: Thrombotic microangiopathy

Ethics approval and consent to participate: Not applicable
Consent for publication: Not applicable
Availability of data and materials: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request
Competing interests: The authors of this manuscript have no conflicts of interest to disclose.
Funding: None
Authors' contributions: PM conceptualised the idea and drafted the manuscript. VS, PR, UK and AM collected the data. SP and VB verified the data. KM and AA reviewed and edited the manuscript. PM interpreted the data and edited the manuscript.
Declaration: All Authors declare that this research did not receive any financial support and do not have any relationships that may pose a conflict of interest
Acknowledgements: None

Davidson B, Bajpai D, Shah S, Jones E, Okyere P, Wearne N, Gumber R, Saxena N, Osafo C. Pregnancy-Associated Acute Kidney Injury in Low-Resource Settings: Progress Over the Last Decade. Semin Nephrol. 2022;42(5):151317. 10.1016/j.semnephrol.2023.151317.
Gautam M, Ahmed A, Mishra P, Azim A, Ahmad A, Dandu H, Agrawal, Avinash, Atam, Virendra, Jaiswar. Shyam. Maternal Mortality due to Pregnancy-Related Acute Kidney Injury (PRAKI); A Study of the Epidemiological Factors and Possible Solutions. J Obstet Gynecol India. 2024;21(1):112. 10.1007/s13224-024-01942-4.
Liu Y, Ma X, Zheng J, Liu X, Yan T. Pregnancy outcomes in patients with acute kidney injury during pregnancy: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2017;17(1):235. 10.1186/s12884-017-1402-9.
Trakarnvanich T, Ngamvichchukorn T, Susantitaphong P. Incidence of acute kidney injury during pregnancy and its prognostic value for adverse clinical outcomes: A systematic review and meta-analysis. Med (Baltim). 2022;101(30):e29563. 10.1097/MD.0000000000029563.
Prakash J, Prakash S, Ganiger VC. Changing epidemiology of acute kidney injury in pregnancy: A journey of four decades from a developing country. Saudi J Kidney Dis Transpl 2019 Sep-Oct;30(5):1118–30. 10.4103/1319-2442.270268
Prasad N, Jaiswal A, Meyyappan J, Gopalakrishnan N, Chaudhary AR, Fernando E, Rathi M, Singh S, Rajapurkar M, Jeloka T, Kishun J, Lobo V. Community-acquired acute kidney injury in India: data from ISN-acute kidney injury registry. Lancet Reg Health Southeast Asia. 2024;21:100359. 10.1016/j.lansea.2024.100359.
Rao S, Jim B. Acute Kidney Injury in Pregnancy: The Changing Landscape for the 21st Century. Kidney Int Rep. 2018;3(2):247–57. 10.1016/j.ekir.2018.01.011.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. 10.1136/bmj.n71.
Wells GA, Shea B, O'Connell D et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed January 11, 2016.
Goplani KR, Shah PR, Gera DN, Gumber M, Dabhi M, Feroz A, Kanodia K, Suresh S, Vanikar AV, Trivedi HL. Pregnancy-related acute renal failure: A single-center experience. Indian J Nephrol. 2008;18(1):17–21. 10.4103/0971-4065.41283. PMID: 20368915; PMCID: PMC2847724.
Najar MS, Shah AR, Wani IA, Reshi AR, Banday KA, Bhat MA, Saldanha CL. Pregnancy related acute kidney injury: A single center experience from the Kashmir Valley. Indian J Nephrol. 2008;18(4):159–61. 10.4103/0971-4065.45291. .PMID: 20142928; PMCID: PMC2813539.
Arora N, Mahajan K, Jana N, Taraphder A. Pregnancy-related acute renal failure in eastern India. Int J Gynaecol Obstet. 2010;111(3):213–6.
1016/j. ijgo.2010.06.026. Epub 2010 Sep 25. PMID: 20870228.
Sivakumar V, Sivaramakrishna G, Sainaresh VV, Sriramnaveen P, Kishore CK, Rani CS, Jagadeesh K. Pregnancy-related acute renal failure: a ten-year experience. Saudi J Kidney Dis Transpl. 2011;22(2):352-3. PMID: 21422644.
Patel ML, Sachan R, Radheshyam, Sachan P. Acute renal failure in pregnancy: Tertiary centre experience from north Indian population. Niger Med J. 2013 May;54(3):191–5. 10.4103/0300-1652.114586. PMID: 23900700; PMCID: PMC3719246.
Pahwa N, Bharani R, ,Kumar R. Post-Partum Acute Kidney Injury. Saudi J Kidney Dis Transpl. 2014;25(6):1244–7.
Godara SM, Kute VB, Trivedi HL, Vanikar AV, Shah PR, Gumber MR, Patel HV, Gumber VM. Clinical profile and outcome of acute kidney injury related to pregnancy in developing countries: a single-center study from India. Saudi J Kidney Dis Transpl. 2014;25(4):906 – 11. 10.4103/1319-2442.135215. PMID: 24969215.
Krishna A, Singh R, Prasad N, Gupta A, Bhadauria D, Kaul A, Sharma RK, Kapoor D. Maternal, fetal and renal outcomes of pregnancy-associated acute kidney injury requiring dialysis. Indian J Nephrol. 2015 Mar-Apr;25(2):77–81. PMID: 25838643; PMCID: PMC4379629.
Gopalakrishnan N, Dhanapriya J, Muthukumar P, Sakthirajan R, Dineshkumar T, Thirumurugan S, Balasubramaniyan T. Acute kidney injury in pregnancy–a single center experience. Ren Fail. 2015;37(9):1476-80. doi: 10.3109/0886022X.2015.1074493. Epub 2015 Sep 3. PMID: 26338215.
Gullipalli P, Srinivasulu N. Spectrum of postpartum kidney injury – A tertiary care center experience in a developing nation. IOSR J Dent Med Sci. 2015;14:92–5.
Eswarappa M, Madhyastha PR, Puri S, Varma V, Bhandari A, Chennabassappa G. Postpartum acute kidney injury: a review of 99 cases. Ren Fail. 2016;38(6):889–doi. 10.3109/0886022X.2016.1164015. Epub 2016 Jun 20. PMID: 27319810.
Mishra V, Goyal Preeti A, Aggarwal Rohina S, Choudhary S, Tanvir T, Dharaiya Nisarg D, Gaddagi Rashmi A. A Single-Centre Experience of Obstetric Acute Kidney Injury. J Obstet Gynaecol India. 2016;66(Suppl 1):207 – 11. doi: 10.1007/s13224-016-0839-5. Epub 2016 Mar 3. PMID: 27651605; PMCID: PMC5016445.
Prakash J, Pant P, Prakash S, Sivasankar M, Vohra R, Doley PK, Pandey LK, Singh U. Changing picture of acute kidney injury in pregnancy: Study of 259 cases over a period of 33 years. Indian J Nephrol. 2016 Jul-Aug;26(4):262–7. 10.4103/0971-4065.161018. PMID: 27512298; PMCID: PMC4964686.
Prakash J, Ganiger VC, Prakash S, Iqbal M, Kar DP, Singh U, Verma A. Acute kidney injury in pregnancy with special reference to pregnancy-specific disorders: a hospital based study (2014–2016). J Nephrol. 2018;31(1):79–85. 10.1007/s40620-017-0466-y. Epub 2018 Jan 4. PMID: 29302904.
Mir MM, Najar MS, Chaudary AM, Azad H, Reshi AR, Banday KA, et al. Postpartum acute kidney injury: Experience of a tertiary care center. Indian J Nephrol. 2017;27:181–4.
Tanwar RS, Agarwal D, Gupta RK, Rathore V, Beniwal P, Joshi P. Malhotra Characteristics and outcome of postpartum acute kidney injury requiring dialysis: A single-center experience from North India. Saudi J Kidney Dis Transpl. 2018 Jul- Aug;29(4):837–845. 10.4103/1319-2442.239663. PMID: 30152420.
Saini S, Chaudhury AR, Divyaveer S, Maurya P, Sircar D, Dasgupta S, Sen D, Bandyopadhyay S, Pandey R. The changing face of pregnancy-related acute kidney injury from eastern part of India: A hospital-based, prospective, observational study. Saudi J Kidney Dis Transpl. 2020 Mar-Apr;31(2):493–502. 10.4103/13192442.284025. PMID: 32394923.
Chowdhary PK, Tibrewal A, Kale SA. Postpartum Acute Kidney Injury in Tertiary Care Center: Single-Center Experience from Central India. Saudi J Kidney Dis Transpl. 2021 Jul-Aug;32(4):1111–1117. 10.4103/1319-2442.338284. PMID: 35229810.
Banerjee A, Mehrotra G. Comparison of Standard Conservative Treatment and Early Initiation of Renal Replacement Therapy in Pregnancy-related Acute Kidney Injury: A Single-center Prospective Study. Indian J Crit Care Med. 2020;24(8):688–94. 10.5005/jp-journals-10071-23537. PMID: 33024376; PMCID: PMC7519595.
Sahay M, Priyashree, Dogra L, Ismal K, Vali S. Pregnancy-related Acute Kidney Injury in Public Hospital in South India: Changing Trends. J Assoc Physicians India. 2022;70(8):11–12. 10.5005/japi-11001-0064. PMID: 36082728.
Sachan R, Shukla S, Shyam R, Patel ML, Verma ML. Role of renal replacement therapy in pregnancy related acute kidney injury and its outcome. J Family Med PrimCare. 2022;11(5):2155–61. 10.4103/jfmpc.jfmpc_1019_21. Epub 2022 May 14. PMID: 35800491; PMCID: PMC9254767.
Yadav S, Chauhan M, Jain D, Aggarwal HK, Yadav RK. Renal Outcomes of Pregnancy-Related Acute Kidney Injury: a Single Centre Experience in India Maedica. (Bucur). 2022;17(1):80–7. 10.26574/maedica.2022.17.1.80. PMID: 35733733; PMCID: PMC9168580.
Sandilya S, Rani KU, Kumar R. Risk factors and fetomaternal outcome in pregnancy-related acute kidney injury. J Family Med Prim Care. 2023;12(12):3346–50. 10.4103/jfmpc.jfmpc_924_23. Epub 2023 Dec 21. PMID: 38361835; PMCID:PMC10866243.
Kharkongor D, Mehrotra S, Solanki V, Singh U, Patel ML, Agarwal S. Acute kidney injury in obstetrics: Hospital-based cohort study. Trop Doct. 2023;53(3):356–61. Epub 2023 Apr 20. PMID: 37078137.
Saxena D et al. Pregnancy Related Acute Kidney Injury: An Exigent Cause of Chronic Kidney Disease in Developing Countries. J Obstet Gynaecol India (2024).
Modi GK, Jha V. The incidence of end-stage renal disease in India: A population-based study. Kidney Int. 2006;70:2131–3.
Shalaby AS, Shemies RS. Pregnancy-related acute kidney injury in the African continent: where do we stand? A systematic review. J Nephrol. 2022;35(9):2175–89. 10.1007/s40620-022-01349-2.

No competing interests reported.

prakiNOS.docx
Supplementary Material 1: Annexure 1: Search strategy, Annexure 2, Table: Quality of studies as per The Newcastle-Ottawa Scale (NOS).
PRISMAPRAKI.pdf
Supplementary Material 2: Prisma checklist of the systematic analysis

Download PDF

Version 1

posted

You are reading this latest preprint version

Pregnancy-associated acute kidney injury as a hidden driver of Chronic kidney disease in developing countries

Status:

Version 1

Abstract

Introduction:

Methods:

Results:

Conclusions:

Figures

Summary at a Glance

Introduction

Methodology

Results

Renal biopsy data

Discussion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1