Worldwide, about 2—8% of pregnancies are complicated by pre-eclampsia, a disorder that is characterised by new-onset hypertension and proteinuria after 20 weeks of pregnancy.1 Pre-eclampsia is associated with risk of adverse fetal outcomes and can progress to severe pre-eclampsia, eclampsia, or death if not diagnosed and treated with delivery. Substantial progress in understanding the pathophysiological mechanisms of the disease has been made in recent years, and changes in concentrations of soluble fms-like tyrosine kinase 1 and other angiogenic factors seem to be key.2 However, mechanisms behind pre-eclampsia and development of acute kidney injury and chronic kidney disease in the mother are less well understood and warrant further discussion.
Although acute kidney injury caused by pre-eclampsia or eclampsia is rare in high-income countries, it complicates 2% of third-trimester pregnancies in India, for example, with pre-eclampsia accounting for 36% of cases (ie, pre-eclampsia associated with acute kidney injury might occur in one of 150 pregnancies).3 Dialysis might be required in up to 50% of cases, and when not available, acute kidney injury is a frequent cause of maternal death. Other major causes of acute kidney injury associated with pregnancy in developing countries include sepsis and major bleeding, whereas less common disorders such as primary renal disease, thrombotic thrombocytopenic microangiopathy, or acute fatty liver of pregnancy are probably relatively more common in developed countries. Although most women with acute kidney injury in pregnancy recover renal function, 7—29% do not fully recover, which can have serious long-term outcomes.3, 4 However, few high-quality studies have assessed the cause, prevalence, and prognosis of acute kidney injury in pregnancy, and more studies are needed to inform strategies for prevention, treatment, and follow-up.
Despite several small studies showing recovery of renal function after so-called pure pre-eclampsia,4 a population-based study from Norway suggested that women who had had pre-eclampsia were at a four-to-five-times increased risk of development of end-stage renal disease during a follow-up of 35 years.5 The risk was significant after exclusion of women with known kidney disease, diabetes, hypertension, or rheumatic disease before pregnancy. Other studies6, 7 showed that pre-eclampsia was a significant risk marker for development of kidney disease, requiring a diagnostic kidney biopsy, but that previous pre-eclampsia was not associated with rapid progression of established kidney disease to end-stage renal disease, suggesting that pre-eclampsia is more strongly associated with the development of kidney disease than with subsequent progression. A Taiwanese study8 also noted an increased risk of chronic kidney disease and end-stage renal disease in women with previous pre-eclampsia. In line with these findings, a meta-analysis concluded that women with previous pre-eclampsia had a four-times increased risk of microalbuminuria 5—10 years after a pre-eclamptic pregnancy compared with women without previous pre-eclampsia.9 This meta-analysis was, however, restricted by inclusion of small studies of variable quality and most of the women either had severe pre-eclampsia or underlying disease such as diabetes mellitus. Associations between pre-eclampsia and subsequent microalbuminuria, which suggest renal injury resulting from pre-eclampsia, need to be verified in large population-based studies.
How pre-eclampsia predisposes to an increased risk of renal disease is not well understood. The issue is complicated by the strong association between pre-eclampsia and cardiovascular risk factors, which also increase risk of kidney disease. That pre-eclampsia might induce primary renal injury is, however, supported by reports that the risk of kidney disease and microalbuminuria after pre-eclampsia seems to be greater than the risk of cardiovascular disease.5, 9, 10 In addition, much the same increase in risk was noted for all types of kidney disease after pre-eclampsia,5, 6 underscoring the hypothesis that a primary renal insult, possibly mediated by extensive endothelial or podocyte injury,11 induces nephron loss and contributes to progression of renal disease. The strong clinical similarity between pre-eclampsia and underlying kidney disease also complicates these studies, because the clinical presentations can be almost identical, especially in multiparous women.12
Developmental and genetic factors are also important determinants of pre-eclampsia risk (as discussed in the accompanying Series), and might themselves be independent risk factors for renal disease. Men and women born in pre-eclamptic pregnancies are at an increased risk of fathering or bearing pre-eclamptic pregnancies, respectively,13 and women born with low birthweight had a 1·5-fold increased risk of pre-eclampsia.14 This intergenerational transfer of risk might suggest genetic predisposition, perinatal programming, or socioeconomic factors, the last of which is an independent risk factor for pre-eclampsia, especially in developing countries.15
Pre-eclampsia is probably an important cause of acute kidney injury and an important risk marker for subsequent chronic kidney disease. Women with previous pre-eclampsia should receive long-term follow-up, especially with respect to hypertension, insulin resistance, and obesity. However, pre-eclampsia might also unmask underlying primary renal disease, and women with pre-eclampsia should be monitored for proteinuria and hypertension within 6—8 weeks of delivery and have a nephrological work-up if these disorders do not resolve.
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