Assessment for Risk of Decline in Kidney Function after a Hypertensive Disorder of Pregnancy

In approximately 10% of all pregnancies, women develop hypertensive disorders, a major cause of maternal morbidity and mortality worldwide. Hypertensive disorders of pregnancy (HDP) occur on a spectrum that ranges from the mild form of gestational hypertension to preeclampsia, clinically characterized by the presence of hypertension in combination with proteinuria, other organ disturbances, and/or intrauterine growth restriction in the second half of pregnancy.

Results of registry-based studies have shown that women with a history of HDP are at increased risk for the development of end-stage renal disease (ESRD). There are few available data on whether the increased incidence of ESRD represents a progressive decline in kidney function after HDP.

Researchers in The Netherlands, led by Nina D. Paauw, MD, conducted a subanalysis of data from the PREVEND (Prevention of Renal and Vascular Endstage Disease) Study, a Dutch population-based cohort with follow-up of five visits ~3 years apart. The subanalysis was designed to assess the incidence of CKD and ESRD and the course of kidney function following HDP in a longitudinal setting. PREVEND included prospective data on kidney function and albuminuria. Results of the analysis were reported in the American Journal of Kidney Diseases [2018;71(5):619-626].

The PREVEND Study included 6000 individuals with urinary albumin excretion ≥10 mg/L and 2592 with urinary albumin excretion <10 mg/L from the population of Groningen, The Netherlands. The current analysis included 2782 of 4301 women who answered the question regarding hypertension during pregnancy. Women who answered “no” to the question of whether they had experienced hypertension during pregnancy were classified as “women with no patient-reported hypertensive pregnancy disorder (nonHDP; n=1805) and women who answered “yes” were classified as “women with a patient-reported hypertensive pregnancy disorder (HDP; n=977).

At the baseline PREVEND visit, median age of women in the HDP group was 50 years, compared with 48 years in the nonHDP group (P=.04). Median follow-up in both groups was 11 years. In both groups, blood pressure was within the normotensive range; however, systolic and diastolic blood pressure were significantly higher in the HDP group compared with the nonHDP group at baseline. There were significant differences between the two groups in ethnicity, body mass index, working status, smoking status, use of oral contraceptives, and cardiovascular comorbid conditions. In the HDP group, laboratory cardiovascular risk markers (glucose, insulin, cholesterol, uric acid, and triglycerides) were significantly higher in the HDP group; use of lipid-lowering medication (but not glucose-lowering medication) was more frequent in the HDP group.

At baseline and during follow-up, blood pressure was significantly higher in the HDP group than in the nonHDP group (Pgroup<.001); blood pressure remained stable in both groups during follow-up. At baseline, the percentage of antihypertensive drug and angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use was higher in the HDP group; use increased significantly in both groups during follow-up (Pgroup<.001 for both drug groups). Over time, the HDP group had a steeper increase in both antihypertensive and specifically ACE inhibitor/ARB drug use compared with the nonHDP group (Pgroup*visit=.03 and Pgroup*visit<.001, respectively).

None of the women in the cohort developed ESRD during follow-up. The prevalence of chronic kidney disease (CKD) was comparable between the two groups at first visit: 12.3% in the non-HDP group versus 14.9% in the HDP group. Results of Cox regression analysis demonstrated that the percentage of women developing CKD during follow-up was comparable in the groups (hazard ratio, 1.04; 95% confidence interval, 0.79-1.37). The incidence rate of CKD after the first visit was 13.2 per 1000 person years in the nonHDP group and 13.6 per 1000 person-years in the HDP group.

At baseline and at follow-up, average estimated glomerular filtration rates (eGFRs) were within the normal range in both groups. Generalized estimating equation analyses demonstrated a group effect (Pgroup=.007); the HDP group had a slight, but significantly lower eGFR at baseline and during follow-up. During follow-up, the eGFR slopes of nonHDP and HDP diverged, with a significant group*visit effect (Pgroup*visit=.05), indicating a significantly steeper decline in the HDP group compared with the nonHDP group. The mean group effect remained significant following adjustment for mean arterial pressure, but was not seen following adjustment for renin-angiotensin system (RAS) blockade. There was no difference between the two groups in 24-hour albuminuria.

Citing study limitations, the researchers identified relying on patient reporting of HDP, resulting in a lack of specific obstetric data that prevented analysis of the effect of pregnancy to follow-up interval, severity of the HDP, and recurrent episodes of HDP on the course of kidney function and development.

In conclusion, the researchers said, “This longitudinal study on kidney function shows that women with a history of HDP have marginally lower eGFRs in the long term, which was not accompanied by higher urinary protein loss or higher incidence of CKD. The increased use of RAS blockade in women after HDP might explain the slightly lower eGFRs and steeper declines in eGFRs after HDP and might additionally have established renoprotective effects. Our results suggest that a history of HDP has only a minor impact on kidney function in later life and they are not in line with the earlier reported increased risk for end-stage kidney disease reported after HDP. The discrepancy between our findings and earlier reports might be explained by the different settings of the studies, in which earlier studies were performed in populations with suboptimal (pre)pregnancy care and/or a higher incidence of end-stage kidney disease.”

Takeaway Points

  1. Dutch researchers utilized data from the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study to assess the incidence of chronic kidney disease (CKD) and end-stage kidney disease as well as the course of kidney function following hypertensive disorders of pregnancy (HDPs).
  2. Women with (n=1805) and without (n=977) patient-reported HDP were included in the current analysis. Mean age was 50 years at baseline and median follow-up was 11 years.
  3. There was no detectable increase in the increase of CKD in the HDP group and the researchers were “unable to identify a significant risk for kidney function decline after patient-reported HDP.”