Elsevier

Journal of Autoimmunity

Volume 79, May 2017, Pages 91-98
Journal of Autoimmunity

Maternal-foetal outcomes in pregnant women with glomerulonephritides. Are all glomerulonephritides alike in pregnancy?

https://doi.org/10.1016/j.jaut.2017.01.008Get rights and content

Highlights

  • Risk for adverse pregnancy outcomes is higher in patients with glomerulonephritis.

  • The increase in risk is present also in patients with glomerulonephritis in remission.

  • Proteinuria and kidney function are the major modulators of risk.

  • Lupus nephropathy shares the main risk pattern with other glomerulonephritides.

  • IgA nephropathy is associated with an increased risk of late-maternal preeclampsia.

Abstract

In spite of the interest for chronic renal diseases (CKD) in pregnancy data on specific diseases is fragmentary; while recent studies analysed the most common glomerulonephritides (GN), none was addressed at GN as a group. The aim of our study was to analyse the main pregnancy-related outcomes in GN patients in a large multicentre cohort.

Patients with a diagnosis of GN were selected from the TOCOS cohort (TOCOS: TOrino Cagliari Observational Study): out of 714 singleton deliveries GN was the diagnosis in 126; lupus GN and IgA nephropathy accounted for 37 and 33 cases; 1418 low-risk singleton deliveries followed-up in the same Centers served as controls (non diabetic, non nephropathic, non obese women, without any other known chronic illness; pregnancies after ovodonation or in vitro fertilisation were excluded, if declared). Multiple regression analysis considered: pre-term (<37 weeks), early preterm delivery (<34 weeks), small for gestational age baby (SGA) and the development of hypertension, proteinuria and preeclampsia (PE) limiting this outcome to the cases without hypertension and proteinuria at baseline.

The population consisted mainly of early CKD stages (stage 1: 61.9%; hypertension 27.8%; proteinuria <0.5 g/day: 55.7%). Age and parity were not different in cases and low-risk controls (age: 31.20 ± 5.5 vs 31.24 ± 5.5 years, primiparous 56.3% vs 57.5%). The incidence of preterm and early preterm delivery was higher in GN versus controls and increased commensurately with CKD stage. In the multivariate analysis, CKD stage was significantly associated with early preterm delivery and development-doubling of proteinuria (odds ratio (OR) around 3 in both), while the OR for baseline hypertension did not reach statistical significance. While the risk pattern did not differ in lupus and non-lupus GN, a significantly higher OR of PE was observed in IgA nephropathy (OR 28.09 versus other GN); risk for pre-term delivery was not increased (OR 0.27 (0.06–1.11)), thereby suggesting “late-maternal” PE.

In conclusion, within the limits of heterogeneity and small numbers, our analysis identifies proteinuria as the most reliable risk marker for adverse pregnancy outcomes and suggests a specific association between IgA nephropathy and late-maternal PE.

Introduction

Growing attention to the complex interactions between chronic renal diseases (CKD) and pregnancy have led to an increased number of studies of pregnancy-related outcomes in various stages of CKD, as well as studies of renal replacement therapy [1], [2], [3].

There is now widespread agreement on the following points: the incidence of adverse pregnancy outcomes increases across CKD stages, but successful pregnancy is possible in patients on dialysis, provided that a high dialysis dose is delivered; the presence of proteinuria and hypertension at baseline are major modulators of the outcomes; there is no increase in malformations in CKD patients, and the risks for neonates are mainly linked to preterm and, especially, early preterm delivery [4], [5], [6], [7], [8], [9].

Of the glomerular diseases (GN), Lupus nephropathy and IgA nephropathy, which occur more frequently, have been the most studied [10], [11], [12], [13], [14], [15], [16], [17]. Less is known however about the differences in outcomes between the various GN, and with respect to the overall population, an issue that is potentially of great importance as this information is needed to tailor clinical practice and optimize resources.

Lupus nephropathy and IgA nephropathy theoretically represent the two extremes of the severity spectrum of GN in pregnancy. However, several points still need to be clarified, among them, the differences and similarities with other GN which occur less frequently and for this reason have seldom been studied [18], [19], [20], [21], [22], [23].

We wished therefore to gather and study data that would enable us to further clarify these issues, and undertook an analysis based on the TOCOS cohort, a large multicentre database, presently encompassing 1019 pregnancies prospectively observed since 2000, with 714 singleton deliveries, 126 of which in women with different forms of GN. The analysis was focused on these cases, with particular attention to the two most common diagnoses: IgA nephropathy and lupus nephropathy, with the related antiphospholipid syndrome [9], [24]. The data will also be discussed in relation to the statistics on 1418 low-risk control singleton deliveries followed-up in the same Centers in the same period (non diabetic, non nephropathic, non obese women, without any other known chronic illness; pregnancies after ovodonation or in vitro fertilisation were excluded, if declared).

Section snippets

Study settings and inclusion criteria

The study analysed data related to all patients with glomerular nephropathies included in the TOCOS database (Torino Cagliari Observational Study). This prospective database includes all pregnant patients diagnosed with CKD before or during pregnancy who were referred to one of the two largest units specializing in the care of pregnant CKD patients in Italy: the Maternal-Foetal Unit of the University Hospital Sant’Anna, Cittá della Salute e della Scienza, Turin, Italy and to the Nephrology Unit

Baseline data

Table 1 reports the baseline data for the overall population of CKD patients with a diagnosis of GN in the TOCOS cohort. In keeping with the early referral policy in the two settings, most of the cases had normal kidney function (stage 1: 61.9%), or were in the grey area (stage 2: 24.6%) and only 13.5% of the patients had a significant reduction in kidney function (stages 3–5); being in CKD stage 1 was significantly less common in IgA nephropathy (45.5%) and in SLE patients (54.1%) than in

Discussion

Even if in recent years much evidence has been gathered, and this has enabled us to better counsel CKD patients who wish to undertake a pregnancy or to guide the follow-up for those who are pregnant, our knowledge is still imperfect, in particular as regards the specific effects of different kidney diseases on pregnancy outcomes.

The present study tries to contribute to filling this gap with regard to glomerulonephritides. Unlike previous studies, which targeted specific diseases, or at the

Conclusions

The presence of a glomerular disease, even in remission (as witnessed by the absence of relevant proteinuria at baseline in over half of the cases) and with normal blood pressure and kidney function, is associated with an increased risk of preterm delivery and of developing proteinuria and hypertension in pregnancy. The risks are modulated by CKD stage, proteinuria and hypertension at baseline, but only the first two of these factors reach statistical significance in our study, and this

Founding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing interests

None.

Acknowledgments

We gratefully acknowledge Susan Finnel for her careful language correction.

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