NephMadness 2015: Obstetric Nephrology Region

Joel Topf, MD; Matthew Sparks, MD; Phyllis August, MD, MPH


March 02, 2015

Editorial Collaboration

Medscape &

In This Article

Preeclampsia Due to CKD vs CKD Due to Preeclampsia

This is a chicken-and-egg–like paradox. We know that CKD is a risk factor for preeclampsia and we know that having preeclampsia predicts future kidney disease. The association of adverse renal and cardiovascular outcomes after preeclampsia is certain and conclusive. What remains to be determined is the etiology of this association.

Does the preeclampsia cause renal and vascular damage that subsequently manifests as renal and cardiovascular disease? Or is preeclampsia merely the first symptom in a patient with underlying kidney disease that would have ultimately presented later even if the patient never became pregnant or developed preeclampsia?

Preeclampsia Due to CKD

Pregnancy in patients with CKD is surprisingly rare. The HUNT II study was an epidemiologic study performed in Nord-Trøndelag, Norway that recorded MDRD eGFRs for 66,149 people.

  • In the subsequent 11 years there were 5,655 singleton pregnancies in women in HUNT II.

    • Only 6 were to women with an eGFR < 60 mL/min

    • None were to women with eGFR < 30 mL/min.

In the HUNT II study, no association was found between decreased eGFR and preeclampsia. However, very few patients had significant CKD. In contrast, women with hypertension and an eGFR < 90 had an increased odds ratio for preeclampsia:

  • OR of 1.82 in women with hypertension and GFR > 90 vs normotensive women

  • OR of 4.24 in women with hypertension and GFR < 90

Most other reports on preeclampsia in CKD have been case series. Cunningham reported 64% of women with severe CKD developed preeclampsia. In a case-control study women with CKD had an OR of 7.2 for preeclampsia.

While the data for increased risk for ESRD and kidney biopsy are compelling, what is surprising is that the results of the biopsies and the etiologies of ESRD are no different than that found in the surrounding background population. One would think that if preeclampsia caused kidney disease, it would cause one particular type of kidney disease that would be identified by providers at dialysis or at least by pathologists at biopsy. This may mean that the association of preeclampsia and future kidney disease is not due to kidney damage from preeclampsia but already existing subtle CKD increasing the risk for both the preeclampsia and subsequent kidney disease.

CKD Due to Preeclampsia

The more one looks at patients with preeclampsia, the more it looks like the disease has significant health effects that last for years after the pregnancy. Hypertension, ischemic heart disease, cardiovascular death (8-fold higher in women with preterm preeclampsia compared to women with either term, or no preeclampsia!), albuminuria, and future kidney biopsy have all been shown to occur at increased rates after preeclampsia.

The most feared renal end point is dialysis dependence. Vikse et al did a comprehensive study of the association between preeclampsia and ESRD in Norway. Of the 570,433 women who had a baby between 1967 and 1991, 20,918 developed preeclampsia with the first pregnancy and 8,531 developed preeclampsia with a second pregnancy.

Preeclampsia during the first pregnancy was associated with a RR of ESRD of 4.7. The authors demonstrated a clear dose-dependent relationship with increased risk with more episodes of preeclampsia. In women with multiple pregnancies, having preeclampsia in a later pregnancy was worse than having preeclampsia in an earlier pregnancy.

Data from Vikse et al.

To strengthen the findings, the authors examined the data after excluding patients with pre-pregnancy hypertension, diabetes or renal or rheumatic disease. Even with these patients censored the risk of ESRD remained, thus strengthening the assertion that the preeclampsia caused the kidney disease rather than the other way around.

The association of pregnancy complications and ESRD is not limited to preeclampsia, having a low birth weight baby or premature delivery has also been associated with increased cardiovascular disease and ESRD.

Could preeclampsia and ESRD have a common cause that puts patients at risk for both diseases? Obesity, hypertension, insulin resistance, and endothelial function are all risk factors for both outcomes. Antiangiogenic factors are another possibility leading to preeclampsia and for CKD.

Despite the accumulating evidence of harm that follows preeclampsia it is important to keep in mind that the vast majority (more than 99%) of women with preeclampsia never develop dialysis-dependent renal failure.


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