Pregnancy outcomes and risk factors analysis in patients with chronic kidney disease: a nested case–control study

Abstract

Background

Chronic kidney disease (CKD) poses significant risks during pregnancy. Accurate early risk prediction remains challenging due to physiological changes, disease heterogeneity, and limitations of various independent renal markers in pregnancy. The aim of this study is to explore the clinical and laboratory variables in early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of CKD.

Methods

A nested case-control study was conducted at Zhongnan Hospital, Wuhan University (2018–2024). We enrolled 187 pregnant women diagnosed with CKD before 12 weeks gestation and 187 controls who were matched in terms of age and major comorbidities but without CKD. CKD staging was based on the first trimester estimated glomerular filtration rate (eGFR) using the CKD-EPI equation and urine albumin-to-creatinine ratio (uACR). Adverse maternal outcomes(AMOs) and adverse neonatal outcomes (ANOs) were compared. Multivariable logistic regression identified predictors.

Results

Key findings showed significantly higher rates of ANOs in CKD patients (61.5% vs. 16.04%, P < 0.01), including preterm birth (48.66% vs. 6.95%, P = 0.023), and SGA (13.90% vs. 2.67%, P < 0.001). AMOs occurred in 48.1% of CKD patients (vs. 4.81% controls, P < 0.001), predominantly preeclampsia (43.85%). Multivariable analysis identified independent risk factors for ANOs: new-onset CKD (OR = 4.447, 95%CI1.949-10.147, P < 0.001), severe proteinuria (OR = 2.487,95%CI 1.112–5.565,P = 0.027), and chronic hypertension (OR = 8.127, 95%CI 2.491–26.512,P = 0.001). These three factors can also affect the outcome of AMO. In addition, the maternal age(OR = 0.886, 95%CI 0.805–0.975, P = 0.013) and a creatinine level (≥ 90µmol/L)(OR = 5.898, 95%CI 1.468–23.702, P = 0.012)are also influencing factors for AMO.

Conclusion

CKD pregnancies pose significantly elevated risks for maternal and neonatal complications. Our findings identify specific early-pregnancy markers – namely serum creatinine (Scr) levels and severe proteinuria (uACR > 300 mg/g) – as critical thresholds for risk stratification, highlighting the necessity for intensified monitoring in this high-risk population.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12884-026-09123-z.

Pregnancy with chronic kidney disease (CKD) is recognized as a complex obstetric condition. Women with CKD are at increased risk of adverse perinatal outcomes, including preeclampsia, preterm birth, and intrauterine growth restriction (IUGR) [1, 2]. Furthermore, CKD may progress during pregnancy [3]. Historically, women with renal dysfunction were considered unsuitable for conception. However, advancements in perinatal and neonatal care have significantly altered this perspective [4]. According to current guidelines and recommendations, pregnancy is not contraindicated for most patients with CKD, although careful evaluation of perinatal risks remains essential. In recent years, the prevalence of pregnancy in women with CKD has increased in China, partly due to advanced maternal age and increased awareness of prenatal screening, with an estimated prevalence of 3% in high-income countries [5]. Consequently, greater attention should be directed toward the pregnancy outcomes and associated risks in this population.

Given the risks and limitations associated with medication use during pregnancy, conception is generally advised for women in early stages of disease or in remission [6, 7]. However, some cases are detected incidentally through prenatal examinations, with patients unaware of their baseline renal dysfunction. Common indicators for assessing CKD severity include estimated glomerular filtration rate (eGFR), serum creatinine (SCr), and urinary protein levels. However, physiological changes during pregnancy limit the applicability of eGFR calculations. The utility of SCr is also compromised by the absence of pregnancy-specific thresholds, making it difficult to stage CKD accurately in pregnant patients. In addition to these limitations, disease heterogeneity, inter-individual variation, and overlapping clinical features with preeclampsia further complicate the evaluation of pregnancy-related risk. Although previous studies have identified disease stage, chronic hypertension, proteinuria, and disease type as potential risk indicators [8–10], the findings remain controversial due to ambiguous CKD staging and imprecise proteinuria quantification. Moreover, few studies have assessed the validity of these predictors during early pregnancy. Current therapeutic recommendations are largely based on anecdotal evidence and small case series. Recently, CKD was redefined and staged using creatinine-based eGFR [7]. Both eGFR and the urine albumin-to-creatinine ratio (uACR) are now recommended for evaluating CKD severity and monitoring disease progression, given their practicality in clinical settings. Therefore, considering the essential roles of eGFR, SCr, and uACR in renal function assessment, it is timely to re-evaluate these parameters during early pregnancy for their predictive value regarding perinatal outcomes. Furthermore, beyond the extent of renal injury, comorbid conditions should also be taken into account when assessing pregnancy-related risks.

In the present study, 187 pregnancies complicated by CKD were retrospectively reviewed and compared with a matched cohort of pregnancies without CKD during the same period. eGFR and uACR were calculated in early pregnancy for initial CKD staging, and their variations were subsequently monitored. This study aimed to evaluate the maternal and fetal outcomes of CKD patients in China and to identify potential indicators for predicting pregnancy risks by comparing outcome variables across different subgroups. The results may aid in identifying patients who require intensive monitoring and management, thereby improving outcomes for pregnancies complicated by CKD.

Methods

Study design

We conducted a retrospective review of the medical records of pregnant women with CKD at Zhongnan Hospital of Wuhan University between January 2018 and December 2024. Women diagnosed with CKD prior to 12 weeks of gestation were included. Patients with incomplete medical records or who experienced early pregnancy loss were excluded. A total of 187 women met the inclusion criteria and were enrolled in the study (Table S1, available as online supplementary material).

After controlling for age and key pre-pregnancy comorbidities (such as chronic hypertension, diabetes, and lupus) through propensity score matching, the study ultimately included 187 matched pairs (CKD group vs. non-CKD group) of pregnant women with comparable baseline characteristics for analysis.

The study was approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (protocol code: 2024198 K). Informed consent was waived for this retrospective analysis of anonymized clinical data, in accordance with the Declaration of Helsinki.

Definitions

CKD was defined as evidence of kidney damage or a glomerular filtration rate (GFR) below 60 ml/min/1.73 m² for at least three months, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [7]. Baseline CKD staging was based on eGFR calculated in the first trimester using the 2021 CKD Epidemiology Collaboration (CKD-EPI) equation. Abnormal proteinuria was defined as protein excretion greater than 300 mg per 24 h or uACR exceeding 30 mg/g, while nephrotic-range proteinuria was defined as uACR equal to or greater than 300 mg/g. The progression of CKD stage is defined as an increase from G1-G2 to G3 or above, or from G3 to G4 or above, or the progression from G4 to requiring maintenance renal dialysis. Acute Kidney Injury(AKI) is defined according to the 2023 “Clinical Practice Guidelines for Acute Kidney Injury in China” (1) with a 26.5 µmol/L increase in serum creatinine within 48 h; (2) a 1.5-fold increase in serum creatinine over the baseline value within 7 days; (3) reduced urine output (< 0.5 ml/kg/h) lasting for more than 6 h. Any of the above conditions can lead to a diagnosis of AKI [11].Lupus nephritis (LN) was defined according to the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) [12]. Diabetic nephropathy (DN) was diagnosed based on the 2020 KDIGO guidelines for CKD [13]. Preeclampsia was diagnosed in accordance with the recommendations of the American College of Obstetricians and Gynecologists [14]. For patients with CKD, superimposed preeclampsia was diagnosed under the following conditions: in a woman with non-proteinuric CKD, the development of new-onset hypertension (blood pressure > 140/90 mmHg) accompanied by proteinuria or maternal organ dysfunction after 20 weeks of gestation; in a woman with proteinuric CKD, the development of new-onset hypertension or maternal organ dysfunction after 20 weeks of gestation; and in a woman with pre-existing hypertension and proteinuria, the development of maternal organ dysfunction after 20 weeks of gestation [14]. The World Health Organization recommends that when the hemoglobin (Hb) concentration during pregnancy is less than 110 g/L, it can be diagnosed as pregnancy-related anemia [15].Based on the Hb level, it is classified as mild anemia (100–109 g/L), moderate anemia (70–99 g/L), severe anemia (40–69 g/L), and extremely severe anemia (< 40 g/L).

Patients

All participants were co-managed by obstetricians and nephrologists, and medication regimens were adjusted as necessary. Physical examinations, laboratory assessments, and ultrasound evaluations were conducted at least once per month to monitor maternal and fetal health. Clinical and laboratory data were extracted from routine medical records. Baseline maternal data were collected at 12 weeks of gestation and included age, obstetric history, pregnancy planning status, CKD stage and type, and medication use. Baseline variables were used to analyze correlations with perinatal outcomes. The presence of comorbidities such as diabetes, chronic hypertension, and SLE was also recorded. Laboratory data included complete blood counts, uACR, 24-hour urinary protein (if available), SCr, blood urea nitrogen (BUN), routine biochemical parameters, and immunological indices. All laboratory tests were conducted using standardized methods. Data from various stages of pregnancy were collected, and pregnancy outcomes were obtained from inpatient records.

Maternal and neonatal outcomes

Adverse maternal outcomes (AMOs) include mortality, CKD stage progression, acute kidney injury(AKI), venous thromboembolism(VTE), moderate or more severe pregnant anemia, and obstetric complications such as pre-eclampsia, eclampsia, and HELLP syndrome. In addition, newly diagnosed or worsened lupus nephritis (LN), diabetic nephropathy(DN), and dialysis requirements were recorded.

Adverse neonatal outcomes (ANOs) were defined as follows: (1) fetal loss, including spontaneous abortion (unexpected fetal loss before 28 weeks of gestation), therapeutic abortion (termination of pregnancy before 28 weeks of gestation due to life-threatening progression of CKD or other obstetric complications), stillbirth (intrauterine fetal death after 20 weeks of gestation not explained by chromosomal abnormalities or anatomic malformation), and neonatal death (death of a live-born infant with a gestational age of more than 28 weeks within 28 days after birth); (2) premature birth (live birth between 28 weeks and 36 weeks and 6 days of gestation) and early preterm delivery (live birth between 28 weeks and 33 weeks and 6 days of gestation); (3) small for gestational age (SGA), defined as a birth weight below the 10th percentile according to gestational age and fetal sex; and (4) neonatal asphyxia, defined as acidosis and an Apgar score below 7 at 1 and/or 5 min after birth. The impact of CKD and its severity on the above maternal and fetal outcomes was analyzed. To evaluate the effect of pregnancy on CKD, patients were followed and assessed at 42 days postpartum.

Sample size and statistical analysis

SPSS 26.0 was used for statistical analysis. The sample size was calculated based on previously reported incidence rates of fetal loss. According to the “Chinese Expert Consensus on Diagnosis and Treatment of Spontaneous Abortion (2020 Edition)”, the overall incidence of spontaneous abortion in the population is 10%, and 80% of these occur in the early stage of pregnancy [16]. Since the control group and the CKD group in this study both excluded cases of fetal loss during the early stage of pregnancy, the predicted fetal loss rate for the control group was 2%. According to the review published by Siligato et al., the fetal loss rates for different types of renal diseases reported by different centers vary significantly, generally ranging from 5.9% to 24%, with most being above 10% [17]. Therefore, we predict that the fetal loss rate in the CKD group will be 10%. A sample size of 180 patients for each group was determined to be sufficient to achieve a significance level of 5% with 90% power. Quantitative variables were described using mean ± standard deviation, and comparisons between two groups were performed using either the t-test or the Wilcoxon rank-sum test, depending on data distribution. Categorical variables were presented as frequency and percentage and analyzed using the chi-square test or Fisher’s exact test, as appropriate. All tests were two-tailed, and a P-value < 0.05 was considered statistically significant. Variables with a P-value < 0.05 in univariate analysis were included in the multivariate analysis. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated.

Results

Clinical and laboratory characteristics of participants in early pregnancy

A total of 187 pregnancies in the CKD group and 187 pregnancies in the control group were included, based on the study’s inclusion and exclusion criteria. The baseline characteristics, clinical and laboratory characteristics of participants are summarized in Tables 1 and 2. This study adopted the “Adult Body Weight Assessment” (WS/T 428–2013) standard issued by the National Health and Family Planning Commission of the People’s Republic of China to define obesity [18]. The specific classifications are as follows: underweight (BMI < 18.5 kg/m²), normal weight (18.5 ≤ BMI < 24.0 kg/m²), overweight (24.0 ≤ BMI < 28.0 kg/m²), and obesity (BMI ≥ 28.0 kg/m²).No significant differences were found between the two groups in terms of mean maternal age, number of pregnancies, educational attainment, and obesity rate. Among participants, 59 in the control group and 88 in the CKD group had comorbidities. The most common comorbidity was chronic hypertension (20.32% vs. 25.13%), followed by diabetes (18.72% vs. 21.93%) and SLE (5.35% vs. 10.70%). However, there was no significant difference in the incidence of these comorbidities between the groups (P > 0.05).

Table 1.

Baseline characteristics of participants at 12 weeks gestation

Variables	Total	Control group	CKD group	P value
Number (%)	374	187	187
Maternal age (years), mean ± SD	30.88 ± 4.45	31.00 ± 5.00	31.10 ± 4.2	0.342
Number of pregnancies	1(0, 2)	1(0, 1.5)	1(0, 2)	0.117
BMI>28 kg/㎡, n(%)	72(19.25)	33(17.65)	39(20.86)	0.431
History of preeclampsia, n(%)	40(10.70)	15(8.02)	25(13.37)	0.094
Educational attainment
Less than high school	33	15	18	0.584
High school graduate or equivalent	43	19	24	0.418
College degree or higher	298	153	145	0.304
General features, n (%)
Maternal age ≥ 35 years	72(19.26)	38(20.32)	34(18.18)	0.60
First pregnancy	134(35.83)	76(40.64)	58(31.02)	0.052
Maternal comorbidities, n (%)
Chronic hypertension	85(22.73)	38(20.32)	47(25.13)	0.267
Diabetes	76(20.32)	35(18.72)	41(21.93)	0.441
SLE	30(8.02)	10(5.35)	20(10.70)	0.057

SLE systemic lupus erythematosus

Table 2.

Clinical and laboratory characteristics of patients with CKD at 12 weeks gestation

	Early stage (G1, G2)	Advanced-stage (G3 to G5)	P value
Type of renal disease, n (%)	154	33
Glomerulonephritis	67(43.51)	9(27.27)	0.085
Lupus nephritis	15(9.74)	2(6.06)	0.739
Diabetic nephropathy	5(3.25)	3(9.09)	0.302
Other types	9(5.84)	1(3.03)	0.821
Unclassified	58(38.31)	18(54.55)	0.073
Whether new onset CKD during pregnancy, n (%)
New onset CKD	59(38.31)	12(36.36)	0.834
Non-new onset CKD	95(61.69)	21(63.64)	0.834
Planed pregnancy in non-new onset CKD	92(96.84)	20(95.24)	1
Baseline renal parameters
SCr(µmol/L), mean ± SD	63.30 ± 17.21	172.97 ± 73.19	< 0.001
BUN(mmol/L), mean ± SD	4.34 ± 2.03	10.11 ± 3.67	< 0.001
Baseline eGFR(ml/min/1.73 m2), mean ± SD	108.71 ± 21.13	38.76 ± 13.06	< 0.001
uACR>30 mg/g, n (%)	137(88.96)	26(78.79)	0.113
Medication During pregnancy, n (%)
Aspirin	68(44.16)	18(54.55)	0.277
LMWH	78(50.65)	17(51.52)	0.928
Corticosteroids	35(22.73)	9(27.27)	0.660
Hydroxychloroquine	32(20.78)	8(24.24)	0.660
Antihypertensive drugs	63(40.91)	15(45.45)	0.631

Data with P < 0.05 are presented in bold

LMWH Low molecular weight heparin

Among patients with CKD, early-stage disease (G1 and G2) accounted for 82.35%, while advanced stages (G3a to G5) accounted for only 17.64% at the time of enrolment at 12 weeks of gestation. This may be due to the tendency of patients with severe disease to terminate the pregnancy. A total of 71 patients were newly diagnosed with CKD after conception (classified as “new-onset CKD”), while 116 patients had a diagnosis prior to pregnancy (classified as “non-new-onset CKD”). Among those with non-new-onset CKD, 112 patients (96.55%) received preconception counselling and had planned pregnancies. The most common CKD subtype was glomerulonephritis (40.64%). Some patients did not have a definitive CKD subtype classification, as they were newly diagnosed during pregnancy. Abnormal BUN levels were observed in 22 patients (11.76%) during early pregnancy. Elevated Scr levels were found in 31 patients (16.58%), and abnormal uACR values were noted in 137 patients (88.96%). Regarding treatment, 61 patients (32.62%) received medications during the first trimester, among whom 40 patients (21.39%) received combination therapy.

Correlation between characteristics of CKD patients in early pregnancy and ANOs

As shown in Table 3, there were 175 live births (93.58%) in the control group and 167 (89.30%) in the CKD group. Among patients with CKD, 72 (38.5%) achieved full-term birth without neonatal complications. ANOs occurred in 115 cases (61.50%), of which 86 cases (45.99%) involved multiple ANOs. Premature birth was the most common ANO, occurring in 48.66% of cases, with early preterm birth accounting for 22.46%. Among all premature births, 86 (45.99%) were medically indicated and 5 (2.67%) were spontaneous. Fetal loss occurred in 20 patients (10.70%), including 2 cases of neonatal death. The mean gestational age in the CKD group was significantly lower than in the control group (35.66 ± 3.15 weeks vs. 38.94 ± 2.20 weeks, P < 0.001). The overall ANO rate in the CKD group was significantly higher than in the control group (P < 0.001). Furthermore, the CKD group showed higher rates of premature birth, SGA, and neonatal asphyxia compared to the control group (P < 0.001). However, no significant difference was observed in fetal loss rates between the two groups (P > 0.05).

Table 3.

Fetal outcomes in pregnant women with or without CKD

	Control group	CKD group
		Total	Early-stage (G1, G2)	Advanced-stage (G3-G5)	P1 value	P2 value	P3 value
Neonatal Outcomes n (%)	187	187	154	33
Without ANOs	157(83.96)	72(38.50)	69(44.81)	3(9.09)	< 0.001	< 0.001	< 0.001
ANOs	30(16.04)	115(61.50)	85(55.19)	30(90.91)	< 0.001	< 0.001	< 0.001
Premature birth	13(6.95)	91(48.66)	69(44.81)	22(66.67)	0.023	< 0.001	< 0.001
Delivery < 34 weeks	6(3.21)	49(26.20)	34(22.08)	15(45.45)	0.006	< 0.001	< 0.001
34 ≤ delivery< 37 weeks	7(3.74)	42(22.46)	35(22.73)	7(21.21)	0.850	< 0.001	< 0.001
SGA	5(2.67)	26(13.90)	21(13.64)	5(15.15)	0.819	< 0.001	< 0.001
Neonatal asphyxia	6(3.21)	33(17.65)	22(14.29)	11(33.33)	0.009	< 0.001	< 0.001
Pregnancy loss	12(6.42)	20(10.70)	12(7.79)	8(24.24)	0.006	0.621	0.139
Spontaneous abortion	4(2.14)	1(0.53)	1(0.65)	0(0)	1	0.493	0.368
Therapeutic abortion	0(0)	12(6.42)	6(3.90)	6(18.18)	0.002	0.008	< 0.001
Stillbirth	5(2.67)	5(2.67)	3(1.95)	2(6.06)	0.463	0.935	1
Neonatal death	3(1.60)	2(1.07)	2(1.30)	0(0)	1	1	1

Data with P < 0.05 are presented in bold

P¹ Total CKD group vs. control group; P² Early-stage CKD group vs. control group; P³ Early-stage vs. advanced-stage CKD group.

As patients with early-stage CKD were generally considered suitable for pregnancy, further analysis was conducted to evaluate their outcomes. It is notable that the ANO rate in the early-stage CKD group was lower than that in the advanced-stage group (P < 0.001), but higher than that in the control group (P < 0.001). As shown in Table 3, although the live birth rates were similar between the early-stage CKD group and the control group (92.20% vs. 93.58%, P > 0.05), the mean gestational age was lower in the former group (36.10 ± 2.98 weeks vs. 38.94 ± 2.20 weeks, P < 0.001).

To identify risk factors for ANOs during early pregnancy, we analyzed correlations between clinical characteristics of early-stage CKD patients at 12 weeks of gestation and ANOs (Table 4). As previously reported, physiological decreases in Scr levels occur during pregnancy. According to the interpretation of the guideline published by Ruan a Scr level of ≥ 60 µmol/L in the second trimester of pregnancy is considered as a sign of impaired renal function [19]. Therefore, two different Scr thresholds were used for stratification in the subsequent analysis. It was found that patients with Scr levels ≥ 60 µmol/L already had a significantly higher ANO rate (P < 0.05). Additionally, univariate analysis revealed that patients with new-onset CKD, glomerulonephritis subtype, heavy proteinuria, or chronic hypertension during early pregnancy had higher rates of ANOs than those without these complications (P < 0.05) (Tables 4 and 5). Patients who had planned their pregnancies, did not have chronic hypertension, or received corticosteroid therapy from early pregnancy had lower fetal loss rates (P < 0.05). In multivariate analysis, new-onset CKD, elevated Scr (≥ 60 µmol/L), and chronic hypertension were identified as independent predictors of ANOs (P < 0.05). These findings suggest that patients with these risk factors require closer monitoring and more intensive management, even when in the early stages of CKD.

Table 4.

Differential analysis between characteristics of early-stage CKD patients during early pregnancy and ANOs

Characteristics of CKD patients	Total	Adverse Neonatal Outcomes			Fetal loss
		With	Without	P value	With	Without	P value
Number	154	85	69		12	142
General features, n (%)
Maternal age ≥ 35 years	27(17.53)	17(20.00)	10(14.49)	0.371	3(25.00)	24(16.90)	0.754
First pregnancy	59(38.31)	28(32.94)	31(44.93)	0.128	4(33.33)	55(38.73)	0.952
Planed pregnancy	148(96.10)	80(94.12)	68(98.55)	0.320	8(66.67)	140(98.59)	< 0.001
New-onset CKD	59(38.31)	46(54.12)	13(18.84)	< 0.001	5(41.67)	54(38.03)	0.803
Type of renal disease, n (%)
Glomerulonephritis	67(43.51)	30(35.29)	37(53.62)	0.023	4(33.33)	63(44.37)	0.662
Lupus nephritis	15(9.74)	9(10.59)	6(8.70)	0.694	1(8.34)	14(9.86)	1
Diabetic nephropathy	5(3.25)	3(3.53)	2(2.90)	1	0(0)	5(3.52)	1
Other types	9(5.84)	3(3.53)	6(8.70)	0.311	1(8.34)	8(5.63)	1
Unclassified	58(38.31)	40(47.06)	18(26.09)	0.008	6(50.00)	52(36.62)	0.358
Complications, n (%)
Chronic hypertension	31(20.13)	27(31.76)	4(5.80)	< 0.001	8(66.67)	23(16.20)	< 0.001
SLE	17(11.04)	9(10.59)	8(11.59)	0.843	0(0)	17(11.97)	0.363
Diabetes	34(22.08)	15(17.65)	19(27.54)	0.141	0(0)	34(23.94)	0.070
Laboratory data, n (%)
SCr≥90µmol/L	19(12.34)	16(18.82)	3(4.35)	0.014	4(33.33)	15(10.56)	0.065
SCr≥60µmol/L	72(46.75)	47(55.29))	25(36.23)	0.018	8(66.67)	64(45.07)	0.255
BUN ≥ 7.14mmol/L	4(2.60)	4(4.71)	0(0)	0.128	1(8.34)	3(2.11)	0.722
uACR>300 mg/g	92(59.74)	62(72.94)	30(43.48)	< 0.001	9(75.00)	83(58.45)	0.415
Medication during early pregnancy, n (%)
Aspirin	68(44.16)	38(44.71)	30(43.48)	0.879	5(41.67)	63(44.37)	0.856
LMWH	78(50.65)	43(50.59)	35(50.72)	0.987	6(50.00)	72(50.70)	0.963
Hydroxychloroquine	32(20.78)	16(18.82)	16(23.19)	0.507	5(41.67)	27(19.01)	0.063
Corticosteroids	35(10.39)	20(23.53)	15(21.74)	0.792	8(66.67)	27(19.01)	0.001
Antihypertensive drugs	63(40.91)	52(61.18)	11(15.94)	< 0.001	8(66.67)	55(38.73)	0.113

Data with P < 0.05 are presented in bold

SLE Systemic lupus erythematosus, Scr Serum creatinine, BUN Blood urea nitrogen, uACR Urine albumin-to-creatinine ratio, LMWH Low molecular weight heparin

Table 5.

Multivariable analysis of characteristics of early-stage CKD patients during early pregnancy with ANOs

Characteristics at 12 weeks gestation	Total	Adverse Neonatal Outcomes			multivariable analysis
		With	Without	P value	OR	95%CI	P value
Number	187	115	72
New-onset CKD	71(37.97)	57(49.57)	14(19.44)	< 0.001	4.447	1.949–10.147	< 0.001
Chronic hypertension	46(24.60)	42(36.52)	4(5.55)	< 0.001	8.127	2.491–26.512	0.001
SCr≥90µmol/L	52(27.81)	46(40.00)	6(8.33)	< 0.001	2.275	0.511–10.123	0.281
SCr≥60µmol/L	105(56.15)	77(66.96)	28(38.89)	< 0.001	1.335	0.591–3.017	0.487
uACR>300 mg/g	106(56.68)	75(65.22)	31(43.06)	0.003	2.487	1.112–5.565	0.027

Data with P < 0.05 are presented in bold

Scr Serum creatinine, uACR Urine albumin-to-creatinine ratio

Correlation between characteristics of CKD patients in early pregnancy and AMOs

Among all participants, 9 (4.81%) in the control group and 90 (48.12%) in the CKD group experienced AMOs during pregnancy, with the difference being statistically significant (P < 0.001). Notably, the incidence of preeclampsia was substantially higher in the CKD group compared with the control group (43.85% vs. 4.81%, P < 0.001). Within the CKD group, patients with chronic hypertension prior to or during the first trimester were more likely to develop preeclampsia (P < 0.05). There were 38 pregnant women in the CKD group who had moderate or higher degree of anemia during pregnancy, while there were 11 cases in the control group. The difference was statistically significant (20.32% vs. 5.88%, p < 0.001). There was 1 case of HELLP syndrome in the CKD group, but not in the control group. There were no deaths, eclampsia or venous thromboembolism in either group. Furthermore, among the 154 patients diagnosed with early-stage CKD during the first trimester, 137 remained in remission throughout pregnancy, whereas 17 progressed to advanced-stage CKD in the second or third trimester. During the 42-day postpartum follow-up, kidney function in 7 patients with disease progression returned to pre-pregnancy levels. Importantly, no patients required dialysis following childbirth. Among all the CKD patients, 6 patients developed AKI. 4 of them occurred after 30 weeks of pregnancy and all delivered healthy babies. Among them, 1 underwent emergency cesarean section due to concurrent placental abruption, 2 due to concurrent fetal distress, and 1 due to elective cesarean Sect.  2 cases of AKI occurred before 23 weeks of pregnancy, 1 resulted in intrauterine fetal death, and 1 underwent therapeutic induction of labor. Multivariable analysis revealed that among patients with early-stage CKD, maternal age, new-onset CKD, chronic hypertension, abnormal Scr levels (≥ 90 µmol/L), and massive proteinuria were independent risk factors for AMOs (Table 6, P < 0.05).

Table 6.

Multivariate analysis of early pregnancy characteristics and AMOs in patients with early stage CKD

Characteristics at 12 weeks gestation	Total	Adverse Maternal Outcomes			Multivariable Analysis
		With	Without	P value	OR	95%CI	P value
Number	187	90	97
Maternal age	31.10 ± 4.20	30.06 ± 3.90	31.56 ± 4.47	0.120	0.886	0.805–0.975	0.013
New-onset CKD	71(37.97)	49(54.44)	22(22.68)	< 0.001	4.441	1.987–9.927	< 0.001
Chronic hypertension	46(24.60)	34(37.78)	12(12.37)	< 0.001	3.937	1.479–10.481	0.006
SCr≥90µmol/L	52(27.81)	38(42.22)	14(14.43)	< 0.001	5.898	1.468–23.702	0.012
uACR>300 mg/g	106(56.68)	63(70.00)	43(44.33)	< 0.001	2.344	1.023–5.368	0.044

Data with P < 0.05 are presented in bold

Scr Serum creatinine, uACR Urine albumin-to-creatinine ratio

Discussion

Given the increasing prevalence and perinatal risks associated with pregnancy complicated by CKD, early identification of high-risk patients is essential for clinical decision-making and stratified management. However, the heterogeneous nature of CKD complicates risk assessment. Although patients with CKD stages 1 and 2 are generally considered suitable for pregnancy, their actual perinatal risk remains controversial. Previous studies were limited by inconsistencies in CKD definitions and data quality, with potential confounding factors, such as comorbidities, not fully accounted for.

In this study, we examined the relationship between clinical characteristics of CKD patients at 12 weeks of gestation and pregnancy outcomes, with a particular focus on early-stage CKD. The rate of ANOs was lower in the early-stage CKD group than in the advanced-stage group, but higher than in the control group. Among patients with early-stage CKD, those with new-onset disease, glomerulonephritis, massive proteinuria, elevated Scr (≥ 60 µmol/L), and chronic hypertension during early pregnancy were more likely to develop ANOs. AMOs were also more frequently observed in patients with these conditions. These findings indicate that even in early-stage CKD, intensive monitoring and management are warranted for patients with such complex presentations.

CKD staging is generally regarded as the most critical factor influencing perinatal outcomes [20]. Patients with advanced-stage CKD exhibit significantly higher rates of preeclampsia, anemia, small-for-gestational-age infants, low 5-minute Apgar scores, and neonatal intensive care unit (NICU) admissions compared to those with early-stage disease [21]. Moreover, a recent systematic review found no evidence that CKD patients in stages 1 to 3 experienced greater declines in kidney function during pregnancy compared to non-pregnant controls [1]. Thus, accurate assessment of renal impairment and CKD stage can inform clinical recommendations regarding pregnancy.

Despite physiological changes during pregnancy that may affect the accuracy of eGFR and serum creatinine, these indicators remain classical measures of kidney function and should be reconsidered for their value in predicting perinatal outcomes [22–25]. Additionally, no superior alternative biomarkers have yet been established [26]. In this study, patients with early-stage CKD (based on eGFR in the first trimester) experienced lower rates of ANOs—including preterm birth, neonatal asphyxia, and pregnancy loss—compared with those with advanced-stage disease. These results suggest that CKD staging based on eGFR during early pregnancy is a useful predictor of perinatal outcomes, particularly for patients without known pre-pregnancy baseline renal function.

Besides eGFR, serum creatinine remains a widely used indicator for assessing renal function during pregnancy. However, its threshold values are unclear due to physiological fluctuations. A population-based serial cross-sectional study reported that the mean Scr level was 60 µmol/L before pregnancy, declining rapidly by 4 weeks of gestation to a nadir of 47 µmol/L between 16 and 32 weeks [27]. A systematic review found that mean Scr values during pregnancy were 84%, 77%, and 80% of non-pregnant values in the first, second, and third trimesters, respectively [28]. It has been suggested that Scr levels ≥ 60 µmol/L during pregnancy may indicate renal dysfunction. In CKD patients, Scr values vary widely; therefore, further stratification based on Scr may improve risk assessment. In our study, patients with Scr levels exceeding 60 or 90 µmol/L exhibited higher rates of ANOs. These findings suggest that a threshold of 60 µmol/L may be sufficient to predict perinatal risks. Although Scr was not identified as an independent predictor of ANOs in multivariate analysis, its predictive potential remains noteworthy.

Recently, increasing attention has been directed toward patients with early-stage CKD, as they are often considered suitable for pregnancy. Nonetheless, perinatal outcomes in this group remain controversial [29]. We speculate that this inconsistency is partly due to the absence of stratified analysis accounting for comorbidities. Factors such as the degree of kidney impairment, hypertension, and proteinuria are well-known contributors to adverse outcomes [30–32], though their interactions are complex and not fully elucidated. Piccoli et al. (2015) reported that chronic hypertension affects between 22% and 54% of pregnant women with CKD [21]. A prospective cohort study observed a stepwise decline in gestational age and birth weight with worsening eGFR and increasing proteinuria levels [33]. Therefore, comorbid conditions should be considered when assessing perinatal risk.

To address this, we further analyzed whether these complex conditions contribute to adverse pregnancy outcomes. We found that patients with early-stage CKD and chronic hypertension exhibited higher rates of both ANOs and AMOs. Additionally, those with a uACR > 300 mg/g from the first trimester were at increased risk of preterm birth and preeclampsia. These findings indicate that among patients with early-stage CKD, those with comorbidities require closer monitoring and more intensive clinical management.

The onset of chronic kidney disease (CKD) is often insidious, and the under recognition of CKD in women is particularly common. Data from the National Health and Nutrition Examination Survey (NHANES) in the United States indicate that CKD awareness among women aged 20 to 49 is approximately 10.2% lower than that among men [34]. This discrepancy may be influenced by diagnostic limitations, as the use of serum creatinine rather than estimated glomerular filtration rate (eGFR) for CKD diagnosis may hinder early detection in women. Their lower baseline serum creatinine levels can mask early signs of CKD. Therefore, it is not uncommon for CKD to be newly diagnosed during early pregnancy.

Compared to women with a pre-pregnancy CKD diagnosis, these patients often lack comprehensive pre-pregnancy counseling, including nephrological and obstetric evaluations, as well as stricter management of pre-existing comorbidities such as hypertension and proteinuria. The adverse outcomes resulting from this oversight are further exacerbated by pregnancy-specific complications, such as hypertensive disorders of pregnancy. These conditions not only worsen underlying CKD but may also lead to acute kidney injury (AKI) during pregnancy, exerting long-term effects on kidney health [35, 36].

Srialluri et al. proposed that early referral to nephrologists, comprehensive family planning guidance, and personalized fertility counseling can reduce the risks of AKI, disease progression, and preeclampsia. Additionally, safe and timely pharmacological interventions may mitigate fetal risks. In other words, by emphasizing pre-pregnancy counseling, addressing modifiable risk factors, and raising awareness among healthcare providers, maternal and fetal health outcomes can be improved, and CKD progression can be slowed [37].

In our study of early-stage CKD patients, we observed a significantly higher rate of corticosteroids use in the fetal loss group compared to the live birth group (66.67% vs. 19.01%, p = 0.001). Additionally, the prevalence of nephrotic syndrome (NS) was significantly higher in the fetal loss group (66.67% vs. 35.21%, p = 0.031). These findings might superficially suggest an association between corticosteroids use during pregnancy and adverse pregnancy outcomes. However, upon deeper analysis, we believe that the activity of CKD itself, rather than corticosteroids exposure, is the underlying cause of the increased risk of fetal loss.

First, the higher proportion of nephrotic syndrome in the fetal loss group provides a critical clue. Nephrotic syndrome is not only a clinical manifestation of CKD but also a marker of highly active and severe glomerular disease. The pathological state it represents—including massive proteinuria, severe hypoalbuminemia, and consequent hypercoagulability—poses a direct threat to pregnancy maintenance. Massive proteinuria and hypoalbuminemia can impair placental perfusion and fetal nutrition, while hypercoagulability significantly increases the risk of micro thrombosis in the placental circulation. These are well-established pathological mechanisms contributing to fetal loss [38]. Thus, patients in the fetal loss group were contending with an internal environment inherently hostile to pregnancy.

Within this context, the higher rate of corticosteroids use in the fetal loss group should be interpreted as a “concomitant indicator” of disease severity rather than an independent risk factor. In clinical practice, the indication for glucocorticoid treatment is precisely disease activity and progression. It is important to note that even within the subgroup of patients with nephrotic syndrome, the fetal loss group had a significantly higher rate of corticosteroids use (62.5% vs. 4%, p < 0.001). This strongly suggests that the NS in this group was more active, less responsive to conservative treatment (refractory NS), or associated with pathological types requiring intensive immunosuppression (such as lupus nephritis or crescentic glomerulonephritis). In other words, it is the “more difficult-to-control” nature of the disease that necessitated more aggressive immunosuppressive therapy, and it is this more aggressive disease state that directly disrupted the physiological homeostasis required for a successful pregnancy.

Admittedly, we cannot completely rule out the possibility that high-dose glucocorticoids may indirectly adversely affect pregnancy by exacerbating hypertension, hyperglycemia, or infection risk. However, attributing these comorbidities solely to the medication is one-sided, as they are also common complications of active CKD, particularly nephrotic syndrome. As an observational study, our research is inherently limited by unavoidable “confounding by indication”—that is, the patients with the most severe disease tend to receive the most intensive treatments, thereby creating a spurious statistical association between the treatment drug and adverse outcomes.

This study has several limitations. It was conducted at a single center and employed a retrospective design. Several factors should be considered when interpreting the results. First, only patients who had completed the first trimester were included; therefore, the impact of CKD on early pregnancy outcomes remains unclear. Second, all participants received multidisciplinary care, whereas patients without follow-up or treatment may experience worse outcomes. Finally, the generalizability of the findings is limited by the sample size. Large-scale, multicenter studies are needed to further validate the predictive value of the identified risk factors.

Conclusion

Despite advances in multidisciplinary management that have enabled many patients with CKD to pursue pregnancy, early identification of high-risk individuals remains essential for improving outcomes through enhanced monitoring and intervention. Comprehensive medical history-taking and appropriate assessments prior to or during early pregnancy may offer valuable insights for risk stratification. In this study, several risk factors for predicting ANOs and AMOs at 12 weeks of gestation were identified. Notably, among patients with early-stage CKD, those with chronic hypertension or massive proteinuria exhibited a higher risk and therefore require more intensive monitoring and management. Although this study has certain limitations, it contributes meaningful evidence toward the early identification of adverse outcomes in pregnant patients with CKD.

Authors’ contributions

TL: Investigation, Data collection, Methodology. TYL: Visualization, Writing- Original draft preparation. XCY: Writing-Reviewing and Editing. LZ provided specialized consultation and participated in the writing. HJC: Conceptualization, Writing-Reviewing and Editing, Supervision. All authors critically reviewed and approved the final version of the manuscript.

Funding

This work was supported by the Hubei Provincial Health and Health Technology Project (Grant No. WJ2025Z011).

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Declarations

Ethics approval and consent to participate

This study was approved by the Medical Ethics Committee, Zhongnan Hospital of Wuhan University (protocol code: 2024198 K) on 9 August 2024. All procedures were performed in accordance with the Declaration of Helsinki and relevant national/international guidelines. The need for informed consent was waived by the ethics committee due to the retrospective nature of the study and the use of anonymized data.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.