Garovic, Vesna D

Background and objectives: Pregnancies in women with systemic lupus erythematosus (SLE) and lupus nephritis are considered high-risk due to high rates of maternal and fetal complications. However, there has not been a formal analysis addressing the issue of maternal deaths in these women. The aim of this study was to perform a literature review of the maternal deaths in women with SLE and lupus nephritis to: (1) identify the main causes of death and (2) discuss possible reasons for these causes, and strategies that may improve patient care and outcomes. Design, setting, participants, and measurement: We performed an extensive electronic literature search from 1962 to 2009 using online databases (PubMed, Embase, Lilacs, Cochrane Controlled Trials Register, Medline, and Science Citation Index). Studies were included if they reported pregnancies in patients with SLE and lupus nephritis with at least one reported maternal death. Results: We identified 13 studies that reported a total of 17 deaths in the 6 week post-partum period that were attributable to SLE and lupus nephritis. In all cases, death occurred in the setting of active disease, and was attributed either to infection in 41.2% ( n = 7), or disease activity in 29.4% ( n = 5). The remaining deaths were due to pulmonary embolus in 11.8% ( n = 2), pregnancy-associated cardiomyopathy in 5.9% ( n = 1), adrenal failure due to abrupt steroid withdrawal in 5.9% ( n = 1), and undefined in 5.9% ( n = 1). Conclusions: All maternal deaths in patients with SLE and lupus nephritis occurred in those with active disease, with disease activity/complications and infections (mainly opportunistic) being the two major causes. The presented evidence further supports timing of pregnancy relative to SLE activity, and the judicious use of immunosuppressive agents in pregnant patients.

Background: Hypertension during pregnancy (HDP) increases the risk of future coronary heart disease (CHD), but it is unknown whether this association is mediated by renal injury. Reduced renal function is both a complication of HDP and a risk factor for CHD. Methods: Logistic regression models were fit to examine the association between a history of HDP and the presence and extent of coronary artery calcification (CAC), a measure of subclinical coronary artery atherosclerosis, in 498 women from the Epidemiology of Coronary Artery Calcification Study (mean age 63.3 ± 9.3 years). Results: Fifty-two (10.4%) women reported a history of HDP. After adjusting for age at time of study participation, HDP was associated with increased serum creatinine later in life ( p = 0.014). HDP was positively associated with the presence of CAC after adjusting for age at time of study participation (OR = 2.7, 95% CI 1.4-5.4). This association was slightly attenuated with adjustment for body size and blood pressure (OR = 2.4, 95% CI 1.2-4.9) but was not further attenuated with adjustment for serum creatinine and urinary albumin/creatinine ratio (OR = 2.6, 95% CI 1.3-5.3). Results were similar for CAC extent. Conclusions: HDP may increase a woman's risk of future CHD beyond traditional risk factors and renal function. Women with a history of HDP should be monitored for potential increased risk of CHD as they age.

Unilateral renal artery stenosis (RAS) leads to atrophy of the stenotic kidney and compensatory enlargement of the contralateral kidney. Although the two-kidney, one-clip (2K1C) model has been extensively used to model human RAS, the cellular responses in the stenotic and contralateral kidneys, particularly in the murine model, have received relatively little attention. We studied mice 2, 5, and 11 wk after unilateral RAS. These mice became hypertensive within 1 wk. The contralateral kidney increased in size within 2 wk after surgery. This enlargement was associated with a transient increase in expression of phospho-extracellular signal-regulated kinase (p-ERK), the proliferation markers proliferating cell nuclear antigen and Ki-67, the cell cycle inhibitors p21 and p27, and transforming growth factor-β, with return to baseline levels by 11 wk. The size of the stenotic kidney was unchanged at 2 wk but progressively decreased between 5 and 11 wk. Unlike the contralateral kidney, which showed minimal histopathological alterations, the stenotic kidney developed progressive interstitial fibrosis, tubular atrophy, and interstitial inflammation. Surprisingly, the stenotic kidney showed a proliferative response, which involved largely tubular epithelial cells. The atrophic kidney had little evidence of apoptosis, despite persistent upregulation of p53; expression of cell cycle regulatory proteins in the stenotic kidney was persistently increased through 11 wk. These studies indicate that in the 2K1C model, the stenotic kidney and contralateral, enlarged kidney exhibit a distinct temporal expression of proteins involved in cell growth, cell survival, apoptosis, inflammation, and fibrosis. Notably, an unexpected proliferative response occurs in the stenotic kidney that undergoes atrophy.

The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and foetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity and maternal and foetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria >0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria <0.5 mg/day and inactive urinary sediment. We identified 58 patients with 90 pregnancies. Compared with pregnancies in SLE patients without renal involvement ( n = 47), pregnancies in patients with active lupus nephritis ( n = 23) were associated with a higher incidence of maternal complications (57% vs 11%, P < 0.001), whereas those with quiescent lupus nephritis ( n = 20) were not (35% vs 11%, P = 0.10). Women with active lupus nephritis were more likely to deliver preterm than women without lupus nephritis, median of 34 weeks vs 40 gestational weeks, respectively ( P = 0.002) and were more likely to suffer foetal loss (35% vs 9%, P = 0.031). Active, but not quiescent, lupus nephritis during pregnancy is associated with a higher incidence of maternal and foetal complications compared with pregnancies in SLE patients without renal involvement.

Evaluation of: Bellamy L, Casas JP, Hingorani AD, Williams DJ: Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Br. Med. J. 335(7627), 974 (2007). Evidence has emerged over the years suggesting that women who develop hypertensive pregnancy disorders, most notably pre-eclampsia, are at an increased risk for cardiovascular disease later in life. In this study, a systematic review and meta-analysis were performed, assessing the future risks of cardiovascular disease, cancer and all-cause mortality in women with a history of pre-eclampsia and eclampsia. Women with a history of pre-eclampsia or eclampsia, compared with women without such a history, had an increased risk for cardiovascular disease, including a fourfold increased risk for hypertension, a twofold increased risk for ischemic heart disease, stroke and deep venous thrombosis, and a 1.5-times higher all-cause mortality. The study suggests that affected women may be eligible for preventive therapies at an earlier age, especially if future studies establish the role of pre-eclampsia as an independent cardiovascular risk factor.

It is estimated that 10% of pregnancies are affected by hypertension worldwide. Approximately one-half of all hypertensive pregnancy disorders are due to preeclampsia, a pregnancy-specific disorder, its distinctive feature being either sudden onset, or worsening of pre-existing proteinuria. It has become increasingly recognized that women with a history of preeclampsia are at increased risk for future cardiovascular disease (CVD), but the mechanisms of this increase in risk are unclear. One possible explanation is that these two conditions share several common metabolic abnormalities as risk factors, including obesity, insulin resistance, and lipid abnormalities that may lead to preeclampsia and CVD at different times of a woman's life. Recent studies have revealed that, similar to CVD, several mediators of endothelial cell dysfunction are up-regulated in preeclampsia. Free radical derived oxidative stress, various inflammatory markers, including neutrophil response, C-reactive protein, and leukocyte adhesion, may contribute to endothelial dysfunction in both preeclampsia and coronary atherosclerosis. Alternatively, preeclampsia itself may induce metabolic and vascular changes that may increase the overall future risk for CVD in affected women. Therefore, at present, it remains unclear whether preeclampsia is a formal risk factor for CVD, or identifies women at increased risk for CVD later in life. Pending large-scale studies aiming to examine the causality of this association, women with a history of preeclampsia should be counseled regarding their increased risks for hypertension and other cardiovascular sequelae later in life, followed closely and treated aggressively for modifiable CVD risk factors.