KH Lee and JH Bae contributed equally as co-first authors.
SM Lee and GJ Cho contributed equally as co-corresponding authors.
Hypertensive disease during pregnancy increases the risk of maternal morbidity and mortality and leads to the development of multi-organ dysfunction, including kidney dysfunction. Complicated pregnancies require careful postpartum management to prevent sequelae. It is believed that kidney injury can consistently occur even after delivery; therefore, defining the chronicity and endpoint is essential for establishing diagnostic criteria. However, data on the prevalence of persistent renal complications following hypertensive disease during pregnancy are limited. In this study, we evaluated the risk of developing renal disorders in patients with a history of hypertensive disease during pregnancy.
Participants who gave birth between 2009 and 2010 were followed up for 8 years after delivery. The risk of renal disorder development after delivery was determined according to a history of hypertensive disease during pregnancy. Different factors that could affect the course of pregnancy, including age, primiparity, multiple pregnancy, preexisting hypertension, pregestational diabetes, hypertensive disease during pregnancy, gestational diabetes, postpartum hemorrhage, and cesarean section, were adjusted for using the Cox hazard model.
Women with hypertension during pregnancy had a higher risk of developing renal disorders after delivery (0.23% vs. 1.38%;
Hypertension during pregnancy can contribute to the development of renal disorders, even after delivery.
Preeclampsia is defined as newly developed hypertension accompanied by one of the end-organ damage signs, such as proteinuria in the last half of pregnancy. The American College of Obstetricians and Gynecologists defines renal insufficiency caused by hypertensive disorders during pregnancy as a serum creatinine level greater than 1.1 mg/dL or a doubled serum creatinine concentration in cases without renal disease [
Several studies have been conducted to define the relationship between high blood pressure during pregnancy and postpartum renal disorders in Europe and America, but data regarding Asian populations are lacking [
Women who gave birth between January 1, 2009 and December 31, 2010 were selected and followed up for a postpartum period of 8 years. Births did not include abortions but only live births. The participants were divided into two subgroups: those with or without hypertensive disease during pregnancy. Hypertensive disease during pregnancy was confirmed using the International Classification of Disease, 10th revision codes (ICD-10 codes) and included gestational hypertension, preeclampsia, eclampsia, and superimposed preeclampsia, but not chronic hypertension, as shown in
The current study is a population-based study and the data were collected from the KNHI. The KNHI is known as the sole public health insurer, which covers the whole population of South Korea and, is, therefore, suitable for nationwide studies [
Continuous variables and frequencies are presented as means and standard deviations. Categorical variables are presented as percentages. Chi-square and
As demonstrated in
Women with hypertensive disease during pregnancy had a higher incidence of renal disorder development 8 years after delivery than those without. Among the 821,038 women who did not develop hypertensive disease during pregnancy, 1,857 developed renal disorders. Furthermore, among the 16,466 women with hypertensive disease during pregnancy, 227 developed renal disorder (0.23% vs. 1.38%;
The correlation between each covariate and occurrence of renal disorders was also analyzed (
Adults aged 35 years or older had a higher risk of developing renal disorders (aHR 1.123, 95% CI 1.005–1.254) than those under 35 years. There was no correlation between primiparity and multiple pregnancies and the risk of developing renal disorders. In addition, the risk of developing renal disorders was greater if hypertension and diabetes were present before or during pregnancy (aHR 3.861, 95% CI 3.400–4.385; aHR 2.302, 95% CI 2.014–2.631; aHR 4.209, 95% CI 3.643–4.864; aHR 1.389, 95% CI 1.101–1.752). Renal disorders occurred more frequently in cases of delivery by cesarean section (aHR 1.311, 95% CI 1.199–1.433).
The incidence of kidney disease 8 years after delivery was higher in women with hypertension during pregnancy than in those without hypertension. This increased risk remained significant even after adjusting for covariates.
These results indicate that women with hypertensive disease during pregnancy are more susceptible to developing renal disorders 8 years after delivery than those without hypertensive disease during pregnancy. Therefore, women with hypertensive disease during pregnancy should be educated about the possibility of developing renal disorders, and the need for early screening and active treatment should be explained. It is also necessary to emphasize that the risk of postpartum renal disease increases in the presence of both hypertension and diabetes before or during pregnancy. In addition, delivery by cesarean section and an age of 35 years or older can be considered predisposing factors for an increased risk of renal complications after delivery. Widespread awareness among clinicians regarding the association between hypertension during pregnancy and renal disorders could improve long-term renal outcomes.
Increased renal function is crucial for maintaining physiological adaptations during pregnancy. During pregnancy, effective renal plasma flow is increased, and renal hyperfiltration causes a 40–60% increase in glomerular filtration rate (GFR) after 20 weeks of pregnancy. In women with hypertension during pregnancy, renal function is significantly decreased due to systemic endothelial dysfunction, which results in proteinuria and lower GFR [
To fully understand the pathophysiology of preeclampsia, researchers have studied genetically modified rats that produce a preeclamptic phenotype. In these rats, renal histologic properties were changed as described above, which, in turn, increased proteinuria due to increased glomerular permeability [
The current study suggests that renal function recovery is hindered after delivery. In addition, underrecovery after delivery may be potentiated by age, mode of delivery, and the presence of other pregnancy complications such as gestational diabetes. Moreover, there is a population-based cohort study suggesting that women with gestational diabetes possess greater risk of developing chronic kidney disease [
A meta-analysis, which included seven cohort studies in European and Middle Eastern regions, was undertaken to accumulate and provide an understanding of whether women with preeclampsia express a greater risk of subsequent renal disorder [
Although studies on the prevalence of persistent renal complications after preeclampsia are continuously accumulating, the findings are conflicting. These findings are often dependent on the sample size, follow-up duration, endpoint definition, and other variables [
The current study is the first to demonstrate that the risk of developing renal disorders after delivery is higher in pregnancies complicated by hypertension in an Asian population. This nationwide, population-based study included a large number of patients. This demonstrates that the results obtained in this study are representative of the South Korean population with a minimum risk of selection bias.
However, the hypothesis proven in this study is limited to the Korean population and cannot be applied to other Asian populations. Furthermore, the outcomes were obtained using ICD-10 codes, which may be less accurate than extracting the outcomes from medical records. In addition, obesity is also known as a potent risk factor for developing renal disorders [
In future, it will be necessary to evaluate whether the same hypothesis can be applied to other Asian populations. Furthermore, studies should be conducted to determine whether hypertensive diseases during pregnancy can contribute to the development of other vasculitis after delivery after delivery. Additional studies could also concentrate on whether the severity of hypertensive disease during pregnancy can increase the risk of postpartum renal complications and various diseases related to vasculitis differently. In addition, a prospective study could be useful for identifying risk factors and identifying at-risk individuals with hypertensive disease during pregnancy who might develop renal disorders after delivery.
In summary, hypertensive disease during pregnancy can be considered a contributing factor to the development of renal disorders, even after delivery, in Korea. A similar relationship in other Asian populations is possible. Therefore, it is important to actively monitor and treat patients complicated by high blood pressure during pregnancy to prevent further decrease in renal function.
The authors report no conflict of interest.
This study was approved by a certified Institutional Review Board (H-2102-127-1198).
Not applicable.
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2021R1F1A1046707) and the Seoul National University Hospital Research Fund (No 0320210230).
Study population.
Renal disorder development 8 years after delivery.
ICD-10 codes for hypertensive disease during pregnancy
Value | |
---|---|
O11 | Pre-eclampsia superimposed on chronic hypertension |
Conditions in O10-complicated by pre-eclampsia | |
Pre-eclampsia superimposed on: hypertension NOS pre-existing hypertension | |
O13 | Gestational (pregnancy-induced) hypertension |
Gestational hypertension NOS | |
Pregnancy-induced hypertension NOS | |
Transient hypertension of pregnancy | |
O14 | Pre-eclampsia |
Superimposed pre-eclampsia (O11) | |
O14.0 | Mild to moderate pre-eclampsia |
O14.1 | Severe pre-eclampsia |
O14.2 | HELLP syndrome |
Combination of hemolysis, elevated liver enzymes and low platelet count | |
O14.9 | Pre-eclampsia, unspecified |
O15 | Eclampsia |
Convulsions following conditions in O10–O14 and O16 | |
Eclampsia with pregnancy-induced or pre-existing hypertension | |
O15.0 | Eclampsia in pregnancy |
O15.1 | Eclampsia in labour |
O15.2 | Eclampsia in the puerperium |
O15.9 | Eclampsia, unspecified as to time period |
Eclampsia NOS |
ICD, International Classification of Disease; NOS, not otherwise specified; HELLP, hemolysis, elevated liver enzymes and low platelet count.
ICD-10 codes for renal disease
Value | |
---|---|
N18 | Chronic kidney disease |
Renal failure | |
N18.1 | Chronic kidney disease, stage 1 |
Kidney damage with normal or increased GFR (≥90 mL/min) | |
N18.2 | Chronic kidney disease, stage 2 |
Kidney damage with mild decreased GFR (60–89 mL/min) | |
N18.3 | Chronic kidney disease, stage 3 |
Kidney damage with moderately decreased GFR (30–59 mL/min) | |
N18.4 | Chronic kidney disease, stage 4 |
Kidney damage with severely decreased GFR (15–29 mL/min) | |
N18.5 | Chronic kidney disease, stage 5 |
End stage kidney disease: in allograft failure, NOS, on dialysis, without dialysis or transplant | |
Renal retinitis (H32.8) | |
Uraemic: apoplexia (I68.8), dementia (F02.8), neuropathy (G63.8), paralysis (G99.8), pericarditis (I32.8) | |
N18.9 | Chronic kidney disease, unspecified |
Chronic renal impairment | |
Chronic uraemia NOS | |
Diffuse sclerosing glomerulonephritis NOS | |
N19 | Unspecified kidney failure |
Renal insufficiency NOS | |
Uraemia NOS | |
Kidney failure due to hypertension (I12.0) | |
Uraemia of newborn (P96.0) |
ICD, International Classification of Disease; GFR, glomerular filtration rate; NOS, not otherwise specified.
Obstetrical characteristics of the participants
Characteristics | Without hypertensive disease during pregnancy | With hypertensive disease during pregancy | |
---|---|---|---|
|
| ||
(n=821,038) | (n=16,466) | ||
Age (yr) | 30.72±3.81 | 31.36±4.30 | <0.0001 |
| |||
≥35 years old | 129,287 (15.75) | 3,675 (22.32) | <0.0001 |
| |||
Primiparity | 414,023 (50.43) | 10,784 (65.49) | <0.0001 |
| |||
Multiple pregnancy | 10,675 (1.30) | 750 (4.55) | <0.0001 |
| |||
Preexisting hypertension | 24,715 (3.01) | 1,948 (11.83) | <0.0001 |
| |||
Pregestational diabetes | 35,723 (4.35) | 1,322 (8.03) | <0.0001 |
| |||
Gestational diabetes | 14,905 (1.82) | 759 (4.61) | <0.0001 |
| |||
Postpartum hemorrhage | 57,078 (6.95) | 1,310 (7.96) | <0.0001 |
| |||
Cesarean section | 293,044 (35.69) | 6,413 (38.95) | <0.0001 |
Values are presented as mean±standard deviation or number (%).
Risk factors with adjusted hazard ratio for developing renal disorder 8-year after delivery
Variable | Adjusted hazard ratio | 95% confidence interval |
---|---|---|
Hypertensive disease during pregnancy | 4.209 | 3.643–4.864 |
≥35 years old | 1.123 | 1.005–1.254 |
Primiparity | 0.981 | 0.898–1.072 |
Multiple pregnancy | 0.892 | 0.636–1.250 |
Preexisting hypertension | 3.861 | 3.400–4.385 |
Pregestational diabetes | 2.302 | 2.014–2.631 |
Gestational diabetes | 1.389 | 1.101–1.752 |
Postpartum hemorrhage | 1.078 | 0.913–1.272 |
Cesarean section | 1.311 | 1.199–1.433 |