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Pregnancy and Glomerular Disease a Systematic Review of the Literature with Management Guidelines

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Pregnancy and Glomerular Disease a Systematic Review of the Literature with Management Guidelines Pregnancy and Glomerular Disease A Systematic Review of the Literature with Management Guidelines Kimberly Blom,* Ayodele Odutayo,* Kate Bramham,† and Michelle A. Hladunewich* Abstract During pregnancy, CKD increases both maternal and fetal risk. Adverse maternal outcomes include progression of underlying renal dysfunction, worsening of urine protein, and hypertension, whereas adverse fetal outcomes *Division of include fetal loss, intrauterine growth restriction, and preterm delivery. As such, pregnancy in young women with Nephrology, CKD is anxiety provoking for both the patient and the clinician providing care, and because the heterogeneous Department of group of glomerular diseases often affects young women, this is an area of heightened concern. In this invited Medicine, review, we discuss pregnancy outcomes in young women with glomerular diseases. We have performed a Sunnybrook Health Sciences Centre, systematic review in attempt to better understand these outcomes among young women with primary GN, we University of Toronto, review the studies of pregnancy outcomes in lupus nephritis, and finally, we provide a potential construct for Toronto, Ontario, management. Although it is safe to say that the vast majority of young women with glomerular disease will have a live Canada; and † birth, the counseling that we can provide with respect to individualized risk remains imprecise in primary GN Department of Renal because the existing literature is extremely dated, and all management principles are extrapolated primarily from Medicine, Division of Transplantation studies in lupus nephritis and diabetes. As such, the study of pregnancy outcomes and management strategies in these Immunology and rare diseases requires a renewed interest and a dedicated collaborative effort. Mucosal Biology, – King’s College, Clin J Am Soc Nephrol 12: 1862 1872, 2017. doi: https://doi.org/10.2215/CJN.00130117 London, United Kingdom Introduction in young women with glomerular diseases. We have Correspondence: Pregnancy is a physiologic stress, wherein failure to performed a systematic review in attempt to better Dr. Michelle A. adapt can result in adverse pregnancy outcomes. understand these outcomes among young women Hladunewich, Sunnybrook Health Systemic and renal vasodilation results in a drop in BP with primary GN, we review the studies of pregnancy fi Sciences Centre, 3rd along with a decrease in renal vascular resistance outcomes in lupus nephritis, and nally, we discuss a Floor, Canadian leading to increased renal plasma flow, and conse- potential construct for management. National Institute for quently, nearly a 50% increase in glomerular filtration. the Blind Kidney Inadequate adaptation occurs in women with under- Centre, 1929 Bayview Avenue, Toronto, ON, lying hypertension and CKD, and is a poor prognostic Systematic Review of Primary Glomerular Canada M4G 3E8. indicator. In general, more resistant hypertension and Diseases Email: michelle. advanced CKD are associated with greater risks of A comprehensive review of pregnancy outcomes hladunewich@ renal disease progression, prematurity, and growth has been conducted in lupus nephritis (2), but there sunnybrook.ca restriction. Data from Italy estimate the risks for are limited data assessing pregnancy risk associated deterioration of kidney function are 7.6%, 12.6%, with other forms of primary GN. Accordingly, we 16.2%, and 20% at stages 1–4, respectively (1). Fur- conducted a systematic review of the literature on thermore, fetal outcomes deteriorate along this same pregnancy outcomes in women with biopsy-proven continuum with preterm delivery before 37 weeks primary glomerular-based diseases. The outcome of gestation increasing from 24% in stage 1 CKD to 89% interest was the frequency of live births according to in stages 4 and 5 CKD and neonatal birth weight primary GN etiology and the influence of baseline dropping by approximately 1300 g between the two characteristics on pregnancy outcomes. Full study groups (mean birth weight 29666659 and 16396870 g methods are in Supplemental Material. In summary, in stage 1 and stages 4 and 5 CKD, respectively) (1). It results from 18 studies, including 887 women and is important to note that only 16% of the patients in this 1414 pregnancies, were abstracted from studies pub- study had glomerular disease, and of those with lished after 1980 (Supplemental Figure 1, Supplemental advanced CKD (stages 3–5), only 11 of 45 had in Table 1). Study heterogeneity was significant, preclud- excess of 1 g urine protein. ing any pooling of data, and baseline characteristics As such, pregnancy in young women with CKD were often not reported or inadequately described, is anxiety provoking for both the patient and the precluding determination of the potential influence of clinician providing care, and because the heteroge- hypertension, renal insufficiency, or proteinuria on neous group of glomerular diseases often affects pregnancy outcomes (Supplemental Table 2). Over young women, this is an area of heightened concern. time, the pathologic descriptions of some glomerular In this invited review, we discuss pregnancy outcomes diseases have also evolved, and the definitions of 1862 Copyright © 2017 by the American Society of Nephrology www.cjasn.org Vol 12 November, 2017 Clin J Am Soc Nephrol 12: 1862–1872, November, 2017 Glomerular Disease in Pregnancy, Blom et al. 1863 important pregnancy complications, such as preeclampsia, (e.g., spontaneous abortion, 8%; preterm delivery, 24%; have changed. As such, the review is narrative, and urgent small for gestational age, 4%; perinatal death, 16% [3]), contemporary data are required. Table 1 below summarizes with hypertension, impaired renal function, and nephrotic- pregnancy outcomes. range proteinuria identified to be associated with the The most commonly reported GN was IgA nephropathy, greatest risk (3,4). Only two studies included women with with 12 studies including 10–136 patients (one study minimal change disease (5,16) or membranous nephropa- included two IgA cohorts) (3–13). The proportion of thy (5,17), and similarly, nephrotic-range proteinuria and women with hypertension at baseline was reported in hypertension in the early stages of pregnancy were asso- eight studies and ranged from 9% to 40%. The proportion ciated with worse pregnancy outcomes. In 33 pregnancies in of women with increased creatinine at study entry was 24 women with membranous nephropathy (17), only 20% rarely reported, and definitions of renal insufficiency (two of 10) of women with .5 g/24 h proteinuria had a live varied. Across all 12 studies, live birth rate ranged from infant born after 32 weeks gestation compared with 91% 70% to 100%. Live birth rates seemed to be lower before (21 of 23) with #5g/24h(P,0.001), suggesting man- 2000 (6,7), but were variable, likely reflecting small study agement of nephrotic syndrome with pregnancy-safe im- sizes and reporting biases in addition to improvements in munosuppression is likely critical and highlighting the neonatal care over the decades. Only five studies reported urgent need for contemporary, collaborative studies to the mean birth weight, which ranged from 2911 to 3200 g, provide informed prepregnancy counseling. and few studies (n55) reported the rate of superimposed preeclampsia, which ranged from 0% to 25%. A minority of studies provided long-term follow-up data. One study Overview of Pregnancy Outcomes in Lupus Nephritis reported both sclerosis and vascular disease to be associated The onset of lupus most frequently occurs in women of with adverse events, but no others attempted to assess the child-bearing age (18), and therefore, it is imperative that relationship between histologic features and outcome (14). nephrologists are comfortable with reproductive counsel- As expected, general themes that emerged included the ing in this subpopulation. Unlike the other primary association of adverse pregnancy outcomes, including glomerular diseases, there are now robust data to inform perinatal death, preterm delivery, and small birth weight, pregnancy outcomes and guide a management approach, with hypertension and renal insufficiency (3–5). In the including a systematic review (2) and two large multicenter second largest study of 118 pregnant women (9), women prospective studies (19,20) as well as numerous smaller with hypertension at baseline (BP$140/90 mmHg) or retrospective analyses. The take-home message from all of impaired renal function (eGFR,70 ml/min per 1.73 m2) these studies is that women with active disease should be were more likely to have an unsuccessful pregnancy. strongly discouraged from conceiving until their lupus is Perinatal mortality was 33% in women with hyperten- controlled. sion compared with 1% in normotensive women and 14% Evidence from meta-analysis data, 37 studies of 2751 in women with renal dysfunction compared with 3% in pregnancies in 1842 women, showed a higher risk of women with normal renal function. The largest study to adverse outcomes, including fetal loss, preeclampsia, date, published in 2010, reported outcomes for 229 preg- preterm delivery, and small for gestational age infants, nancies and compared renal outcomes of 136 pregnant in those with active disease in early pregnancy (2). women with 87 nonpregnant women, all with serum Furthermore, any maternal disease flare and renal flare creatinine levels #1.2 mg/dl at diagnosis (10). Although were estimated to occur in 26% and 16% of pregnan- pregnancy did not affect renal disease progression in this cies,
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