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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="StatPearls [Internet]" /><meta name="citation_title" content="Glomerulonephritis in Pregnancy" /><meta name="citation_publisher" content="StatPearls Publishing" /><meta name="citation_date" content="2024/10/29" /><meta name="citation_author" content="Mugdha Kulkarni" /><meta name="citation_author" content="Sayna Norouzi" /><meta name="citation_author" content="Mohamed Hassanein" /><meta name="citation_author" content="Silvi Shah" /><meta name="citation_pmid" content="39536139" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK609091/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Glomerulonephritis in Pregnancy" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="StatPearls Publishing" /><meta name="DC.Contributor" content="Mugdha Kulkarni" /><meta name="DC.Contributor" content="Sayna Norouzi" /><meta name="DC.Contributor" content="Mohamed Hassanein" /><meta name="DC.Contributor" content="Silvi Shah" /><meta name="DC.Date" content="2024/10/29" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK609091/" /><meta name="description" content="Pregnancy triggers numerous physiological changes, including volume expansion, vasodilation, and changes in hormonal milieu, which are crucial in facilitating the kidneys' adaption to pregnancy. These changes cause a decline in serum creatinine levels, which is most prominent in the second trimester, after which serum creatinine begins to stabilize. Glomerulonephritis during pregnancy may present as acute kidney injury (AKI) or exacerbate preexisting chronic kidney disease (CKD). CKD can affect both maternal and fetal well-being, but data on glomerulonephritis in pregnancy remain limited. Unique kidney-related pathophysiological changes in pregnancy are explored, with a focus on the evaluation and management of glomerulonephritis in this context." /><meta name="og:title" content="Glomerulonephritis in Pregnancy" /><meta name="og:type" content="book" /><meta name="og:description" content="Pregnancy triggers numerous physiological changes, including volume expansion, vasodilation, and changes in hormonal milieu, which are crucial in facilitating the kidneys' adaption to pregnancy. These changes cause a decline in serum creatinine levels, which is most prominent in the second trimester, after which serum creatinine begins to stabilize. Glomerulonephritis during pregnancy may present as acute kidney injury (AKI) or exacerbate preexisting chronic kidney disease (CKD). CKD can affect both maternal and fetal well-being, but data on glomerulonephritis in pregnancy remain limited. Unique kidney-related pathophysiological changes in pregnancy are explored, with a focus on the evaluation and management of glomerulonephritis in this context." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK609091/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-statpearls-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/statpearls/article-169702/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK609091/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/statpearls/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-statpearls-lrg.png" alt="Cover of StatPearls" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>StatPearls [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK609091_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK609091_dtls__"><div>Treasure Island (FL): <a href="https://www.statpearls.com/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">StatPearls Publishing</a>; 2025 Jan-.</div></div><div class="half_rhythm"></div><div class="bk_noprnt"><form method="get" action="/books/n/statpearls/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK609091_"><span class="title" itemprop="name">Glomerulonephritis in Pregnancy</span></h1><p class="contrib-group"><span itemprop="author">Mugdha Kulkarni</span>; <span itemprop="author">Sayna Norouzi</span>; <span itemprop="author">Mohamed Hassanein</span>; <span itemprop="author">Silvi Shah</span>.</p><a data-jig="ncbitoggler" href="#__NBK609091_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK609091_ai__"><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Mugdha Kulkarni</span><sup>1</sup>; <span itemprop="author">Sayna Norouzi</span><sup>2</sup>; <span itemprop="author">Mohamed Hassanein</span><sup>3</sup>; <span itemprop="author">Silvi Shah</span><sup>4</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> University of Cincinnati Medical Center Cincinnati, OH</div><div class="affiliation"><sup>2</sup> Loma Linda University Medical Center, Loma Linda, California</div><div class="affiliation"><sup>3</sup> University of Mississippi Medical Center</div><div class="affiliation"><sup>4</sup> University of Cincinnati, Cincinnati, OH</div></div><p class="small">Last Update: <span itemprop="dateModified">October 29, 2024</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="article-169702.s1"><h2 id="_article-169702_s1_">Continuing Education Activity</h2><p>Pregnancy triggers numerous physiological changes, including volume expansion, vasodilation, and hormonal shifts that support renal adaptation. Patients may either develop de novo glomerulonephritis during pregnancy, or they may have a history of the condition before conception, which complicates pregnancy management. Glomerulonephritis in pregnancy can manifest as acute kidney injury or exacerbate chronic kidney disease, affecting both maternal and fetal outcomes. Focal segmental glomerulosclerosis is the most common glomerulonephritis in pregnancy, followed by IgA nephropathy, antineutrophil cytoplasmic antibodies (ANCA)–related glomerulonephritis, and lupus nephritis.</p><p>Managing glomerulonephritis in pregnancy presents unique challenges due to altered kidney physiology, limited safety data on immunosuppressants, and the need for careful consideration of the physiological changes associated with pregnancy, which may require modifications to diagnostic and treatment strategies. Both diagnostic testing and treatment options must be adapted to accommodate these changes. Evaluation includes testing for antinuclear antibodies (ANA), ANCA, complement levels, anti-dsDNA, anti-phospholipid, and anti-PLA2R antibodies, especially in cases of new-onset proteinuria. Kidney biopsy is recommended if disease progression is suspected or if biopsy results will influence management. Robust data on glomerulonephritis in pregnancy are limited. This activity highlights the kidney-related pathophysiological alterations during pregnancy and focuses on evaluating and managing glomerulonephritis in this context.</p><p>
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<b>Objectives:</b>
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<ul><li class="half_rhythm"><div>Identify the physiological changes that occur during pregnancy and how they affect renal function and glomerulonephritis management.</div></li><li class="half_rhythm"><div>Assess the potential risks and benefits of various treatment options, including the use of immunosuppressants, in the context of pregnancy.</div></li><li class="half_rhythm"><div>Select appropriate monitoring strategies for renal function and potential complications in both the mother and fetus throughout pregnancy.</div></li><li class="half_rhythm"><div>Collaborate with an interdisciplinary healthcare team to provide comprehensive care for pregnant patients with glomerulonephritis.</div></li></ul>
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<a href="https://www.statpearls.com/account/trialuserreg/?articleid=169702&utm_source=pubmed&utm_campaign=reviews&utm_content=169702" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Access free multiple choice questions on this topic.</a>
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</p></div><div id="article-169702.s2"><h2 id="_article-169702_s2_">Introduction</h2><p>Pregnancy triggers numerous physiological changes, including volume expansion, vasodilation, and changes in hormonal milieu, which are crucial in facilitating the kidneys' adaption to pregnancy. These changes cause a decline in serum creatinine levels, which is most prominent in the second trimester, after which serum creatinine begins to stabilize. Glomerulonephritis during pregnancy may present as acute kidney injury (AKI) or exacerbate preexisting chronic kidney disease (CKD). CKD can affect both maternal and fetal well-being, but data on glomerulonephritis in pregnancy remain limited. Unique kidney-related pathophysiological changes in pregnancy are explored, with a focus on the evaluation and management of glomerulonephritis in this context.</p></div><div id="article-169702.s3"><h2 id="_article-169702_s3_">Etiology</h2><p>The causes of glomerular diseases in pregnancy are similar to those in the general population. Etiologies of glomerulonephritis in pregnancy include focal segmental glomerulosclerosis (FSGS), immunoglobulin A (IgA) nephropathy (IgAN), membranous nephropathy, lupus nephritis, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and Goodpasture syndrome (anti-glomerular basement membrane disease).</p><p>Please see the following StatPearls' companion resources for further information:</p><ul><li class="half_rhythm"><div>
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<a href="https://www.statpearls.com/point-of-care/22289" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Focal and Segmental Sclerosis</a>
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</div></li><li class="half_rhythm"><div>
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<a href="https://www.statpearls.com/point-of-care/23357" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IgA Nephropathy</a>
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</div></li><li class="half_rhythm"><div>
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<a href="https://www.statpearls.com/point-of-care/24949" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Membranous Nephropathy</a>
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</div></li><li class="half_rhythm"><div>
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<a href="https://www.statpearls.com/point-of-care/25699" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lupus Nephritis</a>
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</div></li><li class="half_rhythm"><div>
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<a href="https://www.statpearls.com/point-of-care/32717" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ANCA-Associated Vasculitis</a>
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</div></li><li class="half_rhythm"><div>
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<a href="https://www.statpearls.com/point-of-care/22371" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Goodpasture Syndrome</a>
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</div></li></ul></div><div id="article-169702.s4"><h2 id="_article-169702_s4_">Epidemiology</h2><p>Approximately 3% of pregnant women show laboratory evidence of CKD.<a class="bk_pop" href="#article-169702.r1">[1]</a> However, data on glomerular diseases in pregnancy are limited, making the exact incidence and prevalence unclear.</p></div><div id="article-169702.s5"><h2 id="_article-169702_s5_">Pathophysiology</h2><p>Normal physiological changes in pregnancy include an increase in renal plasma flow by up to 80%, a 50% rise in glomerular filtration rate (GFR), and dilation of the pelvicalyceal system.<a class="bk_pop" href="#article-169702.r2">[2]</a> Plasma volume expands by 40% to 50%, and the osmostat resets, leading to a 4 to 5 mmol/L decrease in serum sodium. This reset may be linked to the production of human chorionic gonadotropin.<a class="bk_pop" href="#article-169702.r3">[3]</a></p><p>Despite normoglycemia, proteinuria and glucosuria are expected during pregnancy. These changes contribute to lower serum creatinine levels. Common equations for estimating GFR may underestimate kidney dysfunction, as they do not account for pregnancy-related hyperfiltration. The reference limit for proteinuria in pregnancy is 300 mg/24 hours or a urine protein-to-creatinine ratio (UPCR) of 0.3 mg/mg, compared to 0.15 mg/mg in healthy non-pregnant individuals.<a class="bk_pop" href="#article-169702.r4">[4]</a> Normal serum creatinine levels in pregnancy range between 0.4 and 0.6 mg/dL, varying with muscle mass.<a class="bk_pop" href="#article-169702.r5">[5]</a></p></div><div id="article-169702.s6"><h2 id="_article-169702_s6_">Histopathology</h2><p>For a detailed discussion of the histological findings for each clinical condition, please refer to the StatPearls' companion resources links mentioned in the <b>Etiology</b> section.</p></div><div id="article-169702.s7"><h2 id="_article-169702_s7_">History and Physical</h2><p>Glomerular diseases can have an insidious onset, and physical symptoms may not become apparent until the disease has progressed significantly. Symptoms may include hematuria, edema, frothy urine, hypertension, and, in acute cases, oliguria. Signs and symptoms of glomerular diseases are typically categorized into 2 broad groups—nephrotic syndrome and nephritic syndrome.</p><p>Nephrotic syndrome is characterized by edema, hypoalbuminemia (<3.5 g/dL), hyperlipidemia, and proteinuria exceeding 3.5 g/d. Nephritic syndrome presents with hematuria, mild proteinuria, hypertension, dysmorphic red blood cells in the urine, red cell casts, and edema. Preeclampsia can present with similar symptoms and must be ruled out before starting immunosuppressive therapy.</p></div><div id="article-169702.s8"><h2 id="_article-169702_s8_">Evaluation</h2><p>Glomerulonephritis in pregnancy may present as de novo AKI detected through routine blood tests or as a progression of underlying CKD. As noted above, current formulas used to estimate GFR do not account for the physiological changes of pregnancy. While some authors recommend obtaining a 24-hour urine creatinine to calculate creatinine clearance, this approach can be particularly cumbersome for pregnant patients.<a class="bk_pop" href="#article-169702.r6">[6]</a> Some studies recommend using the 75th percentile of prepregnancy creatinine levels as a threshold to define impaired kidney function during pregnancy.<a class="bk_pop" href="#article-169702.r6">[6]</a><a class="bk_pop" href="#article-169702.r7">[7]</a> A standard protocol, proposed by Maria et al, suggests using a creatinine range of 0.4 to 0.6 mg/dL as the cutoff for normal kidney function in pregnancy.<a class="bk_pop" href="#article-169702.r5">[5]</a></p><p>A UPCR of 0.3 g/g or higher is considered abnormal in pregnancy. Nephrology consultation is recommended for all suspected cases of glomerulonephritis in pregnancy and for patients with a history of the condition, regardless of current disease activity. The optimal frequency and selection of routine blood tests vary across studies.<a class="bk_pop" href="#article-169702.r8">[8]</a><a class="bk_pop" href="#article-169702.r9">[9]</a> Regular outpatient follow-up every 4 to 6 weeks is essential, including monitoring with a basic metabolic panel, urinalysis, UPCR, and serum levels of sodium, potassium, chloride, bicarbonate, urea, and creatinine (see <b>Image.</b> Overview of Glomerulonephritis Management During Pregnancy). A kidney ultrasound is also recommended if not previously obtained.</p><p>Additional tests, including antinuclear antibody (ANA), ANCA, complement levels (C3 and C4), double-stranded DNA (dsDNA) antibodies, antiphospholipid antibodies, and anti-phospholipase A2 receptor antibody (anti-PLA2R), should be ordered for new-onset proteinuria. Each visit should include blood pressure monitoring and a review of home readings for at-risk patients, such as those with a history of preeclampsia or uncontrolled hypertension. Medications should also be reviewed at every visit.</p><p>Counseling is essential, as glomerulonephritis presents unique risks and challenges during pregnancy. Pregnancy should be delayed for at least 6 months after remission begins. Patients with active glomerular disease or CKD face an increased risk of preterm birth, small-for-gestational-age (SGA) neonates, and preeclampsia.<a class="bk_pop" href="#article-169702.r10">[10]</a><a class="bk_pop" href="#article-169702.r11">[11]</a><a class="bk_pop" href="#article-169702.r12">[12]</a> Prepregnancy counseling is critical, as many immunosuppressive medications are teratogenic and must be discontinued before conception.</p><p>For all pregnant patients with new or preexisting glomerulonephritis, counseling should cover the following:</p><ul><li class="half_rhythm"><div>An overview of pregnancy outcomes specific to the underlying glomerulonephritis.</div></li><li class="half_rhythm"><div>Risks of adverse maternal and fetal outcomes. </div></li><li class="half_rhythm"><div>Potential adverse effects of medications prescribed for glomerulonephritis. </div></li><li class="half_rhythm"><div>Risks associated with kidney biopsy, if deemed necessary.</div></li></ul><p>A kidney biopsy is indicated in cases of worsening existing glomerular disease when biopsy findings could alter management or if there is suspicion of significant de novo glomerular disease that may require treatment. The risk of complications from a kidney biopsy is increased during pregnancy, particularly after 20 to 25 weeks, when the risk of bleeding is doubled compared to before 20 weeks.<a class="bk_pop" href="#article-169702.r13">[13]</a><a class="bk_pop" href="#article-169702.r14">[14]</a> </p><p>Indications for biopsy include:</p><ul><li class="half_rhythm"><div>A rapid decline in estimated GFR (eGFR) without a diagnosed cause or suspected worsening of underlying glomerulonephritis.</div></li><li class="half_rhythm"><div>Agreement between the patient and physician that immunosuppression may be necessary to prolong the pregnancy to 32 weeks.</div></li><li class="half_rhythm"><div>The detection of new-onset nephrotic syndrome before fetal viability (24 weeks of gestation), as obtaining a diagnosis can facilitate effective management.</div></li></ul></div><div id="article-169702.s9"><h2 id="_article-169702_s9_">Treatment / Management</h2><p>For patients with glomerulonephritis planning pregnancy, achieving disease remission on either no immunosuppression or pregnancy-safe immunosuppression for 3 to 6 months before conception is recommended. Remission criteria include stable GFR, inactive urine sediment, and proteinuria below 0.5 g/d (via 24-hour collection or spot UPCR). Although some immunosuppressive medications such as azathioprine and tacrolimus have been reported to be relatively safe during pregnancy, rare adverse effects and maternal-fetal complications have been reported with all immunosuppressants, regardless of the agent used. Shared decision-making is essential, involving a thorough discussion of the risks and benefits of immunosuppression with the patient (see <b>Image.</b> Immunosuppressants in Pregnancy and Lactation). </p><p>Optimizing comorbid conditions such as hypertension and diabetes is essential in managing glomerulonephritis during pregnancy. First-line treatments for hypertension include beta-blockers (eg, labetalol) and calcium channel blockers (eg, nifedipine), with hydralazine as a second-line option. Aspirin prophylaxis, starting at 12 weeks of gestation, is recommended to reduce the risk of preeclampsia in pregnant patients with glomerulonephritis.<a class="bk_pop" href="#article-169702.r15">[15]</a> In pregnant patients with severe proteinuria and hypoalbuminemia (<2 g/dL), the risk of thromboembolism rises significantly, warranting prophylaxis with low molecular weight heparin during pregnancy.<a class="bk_pop" href="#article-169702.r5">[5]</a><a class="bk_pop" href="#article-169702.r16">[16]</a></p><p>The literature suggests that FSGS seems to be the most prevalent glomerulonephritis in pregnancy, followed by IgAN, ANCA-related glomerulonephritis, and lupus nephritis.<a class="bk_pop" href="#article-169702.r17">[17]</a><a class="bk_pop" href="#article-169702.r18">[18]</a></p><p>
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<b>Focal Segmental Glomerulosclerosis </b>
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</p><p>Pregnant patients with known FSGS are at higher risk for complications such as preeclampsia and preterm delivery. Notably, FSGS is a common histopathological finding in preeclampsia. The timing of proteinuria onset, along with coexisting hypertension, can help differentiate preeclampsia-related FSGS from isolated FSGS. Laboratory markers, such as the soluble FMS-like tyrosine kinase receptor 1 (sFlt-1)/placental growth factor (PlGF) ratio, can also aid in identifying preeclampsia.<a class="bk_pop" href="#article-169702.r19">[19]</a> A study reported an 11% risk of fetal loss and a 10% risk of premature delivery in patients with FSGS.<a class="bk_pop" href="#article-169702.r20">[20]</a> Oral steroids with a gradual taper are typically used during pregnancy unless contraindicated, such as in cases of uncontrolled diabetes. For steroid-resistant cases, calcineurin inhibitors may be considered, although the risks, including gestational diabetes, should be discussed with the patient. Case reports suggest that the collapsing variant of FSGS in pregnant patients has shown a favorable response to treatment.<a class="bk_pop" href="#article-169702.r21">[21]</a> </p><p>
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<b>IgA Nephropathy </b>
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</p><p>IgAN may present with microscopic or macroscopic hematuria, asymptomatic hematuria with proteinuria, or, in rare cases, AKI. IgAN is associated with higher risks of adverse fetal-maternal outcomes, including preeclampsia, SGA neonates, preterm birth, and cesarean delivery.<a class="bk_pop" href="#article-169702.r5">[5]</a> A large meta-analysis found that pregnant patients with preserved renal function did not experience significant renal function loss but had higher rates of preeclampsia, low birth weight neonates, preterm delivery, and infant loss.<a class="bk_pop" href="#article-169702.r22">[22]</a> In addition, studies indicate that pregnant patients with IgAN and stage 3 or higher CKD are at risk for rapid GFR decline.<a class="bk_pop" href="#article-169702.r23">[23]</a><a class="bk_pop" href="#article-169702.r24">[24]</a></p><p>Careful monitoring is appropriate for patients with mild, stable disease. Women with IgAN at stage 3 or higher should be informed about the risk of CKD progression and monitored closely. For those with progressive disease or rapidly advancing glomerulonephritis (crescentic IgAN) requiring treatment, corticosteroid pulse doses with taper may be used. Newer drugs, such as enteric-coated budesonide and sparsentan, have received approval for IgAN from the United States Food and Drug Administration (FDA), but they have not been tested in pregnancy, and sparsentan is contraindicated in pregnant patients. Budesonide may be used in select cases, but potential risks, such as hypoadrenalism in infants, should be discussed. Case reports have noted the use of tacrolimus for treating IgAN during pregnancy.<a class="bk_pop" href="#article-169702.r25">[25]</a> However, conclusively, corticosteroids remain the primary treatment for IgAN in pregnant patients.</p><p>
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<b>Membranous Nephropathy</b>
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</p><p>Literature on membranous nephropathy is limited. Similar to other causes of nephrotic syndrome, membranous nephropathy is associated with adverse fetal and maternal outcomes. When phospholipase A2 receptor (PLA2R) antibodies are present along with the typical nephrotic syndrome presentation, a kidney biopsy is unnecessary for diagnosing primary membranous nephropathy. However, secondary membranous nephropathy must be excluded through appropriate screening and serological workup. The role of PLA2R antibodies as predictors of adverse outcomes remains unclear.</p><p>Patients with proteinuria less than 3.5 g/dL, serum albumin greater than 3.0 g/dL, and eGFR above 60 mL/min/1.73 m² can be safely monitored without immunosuppression. For those experiencing AKI or worsening proteinuria, treatment options include corticosteroids, calcineurin inhibitors, and rituximab (only during the first trimester). Case reports have demonstrated positive outcomes with tacrolimus treatment throughout pregnancy.<a class="bk_pop" href="#article-169702.r26">[26]</a><a class="bk_pop" href="#article-169702.r27">[27]</a> Additionally, thromboembolism prophylaxis with enoxaparin should be considered for pregnant patients, particularly if serum albumin is below 2.5 g/dL.</p><p>
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<b>Lupus Nephritis </b>
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</p><p>Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age, with approximately one-third of these women developing lupus nephritis.<a class="bk_pop" href="#article-169702.r28">[28]</a> Ideally, pregnancy should be considered only after a minimum of 6 months of disease quiescence. Teratogenic medications, such as mycophenolic acid analogs, should be discontinued, allowing for an adequate wash-out period of at least 6 to 8 weeks before conception.<a href="https://www.statpearls.com/Keywords/UserViewPopup/171067#link_37915962" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">[29]</a> Maternal complications in women with SLE include an earlier onset of preeclampsia, lupus flares, and preterm delivery. Fetal complications may involve abortions, stillbirths, and intrauterine growth restriction. One study reported adverse pregnancy outcomes in 19% of pregnancies, with fetal death occurring in 4%, preterm delivery in 9%, and SGA neonates in 10% of patients. The presence of lupus anticoagulants, use of antihypertensive medications, and low platelet counts have been associated with adverse outcomes. Additionally, maternal flares, higher disease activity, and increases in complement C3 levels further elevate fetal-maternal risk.<a class="bk_pop" href="#article-169702.r29">[29]</a></p><p>Pregnant patients with SLE should be screened for anti-Ro (SSA) and anti-La (SSB) antibodies because of the risk of complete congenital heart block in the neonate. Additionally, screening for antiphospholipid antibodies should be performed early in pregnancy due to an increased risk of fetal loss.<a class="bk_pop" href="#article-169702.r5">[5]</a> Kidney biopsy during pregnancy is indicated for worsening proteinuria, AKI with active urinary sediment, or suspicion of concurrent conditions such as thrombotic microangiopathy. If de novo lupus nephritis is diagnosed during pregnancy, the goal of induction and maintenance therapy should be to support the continuation of the pregnancy until the fetus matures as much as possible. Treatment options for lupus nephritis include glucocorticoids, calcineurin inhibitors (tacrolimus and cyclosporine), and azathioprine, along with rituximab in the first trimester. Notably, it is advisable to continue hydroxychloroquine during pregnancy to reduce the risk of complications. Additionally, low-dose aspirin should be initiated before 16 weeks of gestation.<a class="bk_pop" href="#article-169702.r30">[30]</a><a class="bk_pop" href="#article-169702.r31">[31]</a> </p><p>
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<b>Antineutrophil Cytoplasmic Antibody-Associated Vasculitis</b>
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</p><p>AAV is rare in individuals of reproductive age and encompasses granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. Associated adverse fetal and maternal outcomes include a preterm birth rate of 20% to 50%, intrauterine growth restriction in 20% of cases, cesarean section delivery in 25%, and hypertension affecting 21% of patients.<a class="bk_pop" href="#article-169702.r32">[32]</a><a class="bk_pop" href="#article-169702.r33">[33]</a> Before conception, the patient should be in remission while receiving a pregnancy-compatible medication. Glucocorticoids are considered a relatively safe treatment option for AAV during pregnancy.</p><p>Managing de novo AAV during pregnancy can be complex and challenging. Rituximab and corticosteroids may be used to induce remission. Plasma exchange should be considered for patients with rapidly declining GFR or those experiencing life- or organ-threatening manifestations.<a class="bk_pop" href="#article-169702.r34">[34]</a> In such cases, it is essential to discuss the risks and benefits of continuing the pregnancy with the patient. The safety of plasma exchange is comparable to that of the general population, provided there is no maternal hypotension.<a class="bk_pop" href="#article-169702.r35">[35]</a> Medications considered relatively safe during pregnancy include azathioprine, corticosteroids, and rituximab during the first trimester for maintenance therapy. However, newer agents such as avacopan and mepolizumab should be avoided during pregnancy due to insufficient data on their safety.</p><p>
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<b>Anti-Glomerular Basement Membrane Glomerulonephritis </b>
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</p><p>Anti-glomerular basement membrane glomerulonephritis typically presents as rapidly progressive glomerulonephritis, with or without pulmonary hemorrhage. There are limited case reports of this condition occurring during pregnancy, most of which involved patients requiring dialysis.<a class="bk_pop" href="#article-169702.r36">[36]</a><a class="bk_pop" href="#article-169702.r37">[37]</a> If anti-glomerular basement membrane glomerulonephritis is suspected, a kidney biopsy should be performed to establish a definitive diagnosis. Treatment options include plasmapheresis, glucocorticoids, and rituximab, with no maintenance therapy necessary. </p></div><div id="article-169702.s10"><h2 id="_article-169702_s10_">Differential Diagnosis</h2><p>When assessing glomerular diseases in pregnancy, it is crucial to differentiate them from pregnancy-related conditions that present with overlapping features.</p><ul><li class="half_rhythm"><div>Preeclampsia: This condition presents with hypertension and proteinuria after 20 weeks of gestation. Preeclampsia can lead to AKI, hemolytic anemia, and thrombocytopenia, while urine sediment is typically bland. Eclampsia is characterized by the onset of seizures or coma during pregnancy or the postpartum period.</div></li></ul><ul><li class="half_rhythm"><div>HELLP syndrome: HELLP (<b>h</b>emolysis, <b>e</b>levated liver enzymes, and <b>l</b>ow <b>p</b>latelets) syndrome can be a severe form of preeclampsia, resulting in multiorgan failure and coagulopathy.</div></li></ul><ul><li class="half_rhythm"><div>Acute fatty liver of pregnancy: This condition occurs in the third trimester, primarily affecting susceptible individuals. Clinical features include fever, nausea, vomiting, jaundice, hypertension, transaminitis, and encephalopathy. Laboratory findings may reveal hypoglycemia, coagulopathy, and elevated liver enzymes. Isolated renal involvement is uncommon in acute fatty liver of pregnancy.</div></li></ul><ul><li class="half_rhythm"><div>Thrombotic microangiopathy: Pregnancy-associated thrombotic microangiopathy is characterized by the presence of platelet and fibrin thrombi in the microcirculation, along with thrombocytopenia, microangiopathic hemolytic anemia, and renal and neurologic dysfunction. Hemolytic uremic syndrome (HUS) is more commonly observed in the postpartum period, while thrombotic thrombocytopenic purpura (TTP) often occurs during the second or third trimester. A kidney biopsy may be necessary to differentiate HUS/TTP from HELLP syndrome, although it poses risks in the presence of thrombocytopenia. Nonetheless, a kidney biopsy can provide valuable insights to guide treatment options, including plasma exchange or administration of eculizumab.</div></li></ul></div><div id="article-169702.s11"><h2 id="_article-169702_s11_">Toxicity and Adverse Effect Management</h2><p>Rituximab is generally considered safe during the first trimester of pregnancy due to its IgG1 component, as placental transfer is not believed to occur until around the 16th week of gestation. Rituximab has a half-life of approximately 18 to 22 days and is typically eliminated within 3 to 4 months after the last dose. Because it can deplete B cells, if the drug is needed during the later stages of pregnancy, neonatal B-cell counts should be closely monitored until the infant is 6 months old.<a class="bk_pop" href="#article-169702.r38">[38]</a></p><p>Tacrolimus is considered safe during pregnancy, and maintaining therapeutic levels is essential to reduce the risk of preterm births.<a class="bk_pop" href="#article-169702.r39">[39]</a><a class="bk_pop" href="#article-169702.r40">[40]</a> Monitoring renal function and potassium levels in neonates exposed to tacrolimus has also been recommended.<a class="bk_pop" href="#article-169702.r41">[41]</a> Similarly, cyclosporine is regarded as relatively safe for use during pregnancy.<a class="bk_pop" href="#article-169702.r42">[42]</a><a class="bk_pop" href="#article-169702.r43">[43]</a></p></div><div id="article-169702.s12"><h2 id="_article-169702_s12_">Deterrence and Patient Education</h2><p>Pregnancy in patients with glomerulonephritis poses significant challenges and can be a source of anxiety for both patients and healthcare providers. The lack of comprehensive data and the limited availability of medications safe for use during pregnancy further complicate decision-making. Patients should receive education about their treatment options, potential complications, and expected pregnancy outcomes. Optimal management requires interdisciplinary coordination among gynecologists, rheumatologists, nephrologists, maternal-fetal medicine specialists, and neonatologists.</p></div><div id="article-169702.s13"><h2 id="_article-169702_s13_">Enhancing Healthcare Team Outcomes </h2><p>Glomerulonephritis during pregnancy poses significant challenges for both patients and the healthcare team. Ethical concerns prevent the inclusion of pregnant patients in clinical trials, resulting in a lack of evidence-based guidelines. Effective management hinges on shared decision-making and collaboration among primary care physicians, nephrologists, gynecologists, rheumatologists, and specialists in high-risk maternal-fetal medicine to ensure patient-centered care.</p><p>Ethical considerations are crucial in determining treatment options while respecting patient autonomy in decision-making. Clearly defining responsibilities within the interprofessional healthcare team allows each member to contribute their specialized knowledge and skills to optimize patient care. Effective communication among healthcare team members fosters a collaborative environment where information is shared, questions are welcomed, and concerns are promptly addressed.</p><p>Care coordination is essential for providing seamless and efficient patient care. Physicians, advanced practitioners, nurses, pharmacists, and other healthcare professionals must collaborate to streamline the patient’s journey from diagnosis through treatment and follow-up. This coordinated approach minimizes errors, reduces delays, and enhances patient safety, ultimately improving outcomes and delivering patient-centered care that prioritizes the well-being and satisfaction of pregnant patients with glomerulonephritis.</p></div><div id="article-169702.s14"><h2 id="_article-169702_s14_">Review Questions</h2><ul><li class="half_rhythm"><div>
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<a href="https://www.statpearls.com/account/trialuserreg/?articleid=169702&utm_source=pubmed&utm_campaign=reviews&utm_content=169702" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Access free multiple choice questions on this topic.</a>
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</div></li><li class="half_rhythm"><div>
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</div></li></ul></div><div class="floats-group" id="article-169702.s15"><div class="iconblock whole_rhythm clearfix ten_col fig" id="figarticle169702imagef1" co-legend-rid="figlgndarticle169702imagef1"><a href="/books/NBK609091/figure/article-169702.image.f1/?report=objectonly" target="object" title="Figure" class="img_link icnblk_img figpopup" rid-figpopup="figarticle169702imagef1" rid-ob="figobarticle169702imagef1"><img class="small-thumb" src="/books/NBK609091/bin/Screenshot__2024-11-22__at__1.04.57xPM.gif" src-large="/books/NBK609091/bin/Screenshot__2024-11-22__at__1.04.57xPM.jpg" alt="Overview of Glomerulonephritis Management During Pregnancy" /></a><div class="icnblk_cntnt" id="figlgndarticle169702imagef1"><h4 id="article-169702.image.f1"><a href="/books/NBK609091/figure/article-169702.image.f1/?report=objectonly" target="object" rid-ob="figobarticle169702imagef1">Figure</a></h4><p class="float-caption no_bottom_margin">Overview of Glomerulonephritis Management During Pregnancy. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BP, blood pressure; CKD, chronic kidney disease; MRA, mineralocorticoid receptor antagonist. <a href="/books/NBK609091/figure/article-169702.image.f1/?report=objectonly" target="object" rid-ob="figobarticle169702imagef1">(more...)</a></p></div></div></div><div class="floats-group" id="article-169702.s16"><div class="iconblock whole_rhythm clearfix ten_col fig" id="figarticle169702imagef2" co-legend-rid="figlgndarticle169702imagef2"><a href="/books/NBK609091/figure/article-169702.image.f2/?report=objectonly" target="object" title="Figure" class="img_link icnblk_img figpopup" rid-figpopup="figarticle169702imagef2" rid-ob="figobarticle169702imagef2"><img class="small-thumb" src="/books/NBK609091/bin/Screenshot__2024-11-22__at__1.00.51xPM.gif" src-large="/books/NBK609091/bin/Screenshot__2024-11-22__at__1.00.51xPM.jpg" alt="Immunosuppressants in Pregnancy and Lactation" /></a><div class="icnblk_cntnt" id="figlgndarticle169702imagef2"><h4 id="article-169702.image.f2"><a href="/books/NBK609091/figure/article-169702.image.f2/?report=objectonly" target="object" rid-ob="figobarticle169702imagef2">Figure</a></h4><p class="float-caption no_bottom_margin">Immunosuppressants in Pregnancy and Lactation. Contributed by M Kulkarni, MD  </p></div></div></div><div id="article-169702.s17"><h2 id="_article-169702_s17_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="article-169702.r1">Munkhaugen J, Lydersen S, Romundstad PR, Widerøe TE, Vikse BE, Hallan S. Kidney function and future risk for adverse pregnancy outcomes: a population-based study from HUNT II, Norway. <span><span class="ref-journal">Nephrol Dial Transplant. </span>2009 Dec;<span class="ref-vol">24</span>(12):3744-50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19578097" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19578097</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="article-169702.r2">Cheung KL, Lafayette RA. 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Pregnancies in women with antineutrophil cytoplasmatic antibody associated vasculitis. <span><span class="ref-journal">Curr Opin Rheumatol. </span>2024 Jan 01;<span class="ref-vol">36</span>(1):16-20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/37682057" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37682057</span></a>]</div></dd><dt>33.</dt><dd><div class="bk_ref" id="article-169702.r33">Singh P, Dhooria A, Rathi M, Agarwal R, Sharma K, Dhir V, Nada R, Minz R, Suri V, Jain S, Sharma A. Successful treatment outcomes in pregnant patients with ANCA-associated vasculitides: A systematic review of literature. <span><span class="ref-journal">Int J Rheum Dis. </span>2018 Sep;<span class="ref-vol">21</span>(9):1734-1740.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30345645" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30345645</span></a>]</div></dd><dt>34.</dt><dd><div class="bk_ref" id="article-169702.r34">Floege J, Jayne DRW, Sanders JF, Tesar V, Balk EM, Gordon CE, Adam G, Tonelli MA, Cheung M, Earley A, Rovin BH. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis. <span><span class="ref-journal">Kidney Int. </span>2024 Mar;<span class="ref-vol">105</span>(3):447-449.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/38388147" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 38388147</span></a>]</div></dd><dt>35.</dt><dd><div class="bk_ref" id="article-169702.r35">Wind M, Gaasbeek AGA, Oosten LEM, Rabelink TJ, van Lith JMM, Sueters M, Teng YKO. Therapeutic plasma exchange in pregnancy: A literature review. <span><span class="ref-journal">Eur J Obstet Gynecol Reprod Biol. </span>2021 May;<span class="ref-vol">260</span>:29-36.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/33713886" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33713886</span></a>]</div></dd><dt>36.</dt><dd><div class="bk_ref" id="article-169702.r36">Kai H, Usui J, Tawara T, Takahashi-Kobayashi M, Ishii R, Tsunoda R, Fujita A, Nagai K, Kaneko S, Morito N, Saito C, Hamada H, Yamagata K. Anti-glomerular Basement Membrane Glomerulonephritis During the First Trimester of Pregnancy. <span><span class="ref-journal">Intern Med. </span>2021 Mar 01;<span class="ref-vol">60</span>(5):765-770.</span> [<a href="/pmc/articles/PMC7990629/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7990629</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32999239" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32999239</span></a>]</div></dd><dt>37.</dt><dd><div class="bk_ref" id="article-169702.r37">Kafagi AH, Li AS, Jayne D, Brix SR. Anti-GBM disease in pregnancy. <span><span class="ref-journal">BMJ Case Rep. </span>2024 Apr 30;<span class="ref-vol">17</span>(4)</span> [<a href="/pmc/articles/PMC11085961/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC11085961</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/38688578" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 38688578</span></a>]</div></dd><dt>38.</dt><dd><div class="bk_ref" id="article-169702.r38">Perrotta K, Kiernan E, Bandoli G, Manaster R, Chambers C. Pregnancy outcomes following maternal treatment with rituximab prior to or during pregnancy: a case series. <span><span class="ref-journal">Rheumatol Adv Pract. </span>2021;<span class="ref-vol">5</span>(1):rkaa074.</span> [<a href="/pmc/articles/PMC7819866/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7819866</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33521513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33521513</span></a>]</div></dd><dt>39.</dt><dd><div class="bk_ref" id="article-169702.r39">Jain AB, Reyes J, Marcos A, Mazariegos G, Eghtesad B, Fontes PA, Cacciarelli TV, Marsh JW, de Vera ME, Rafail A, Starzl TE, Fung JJ. Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center's experience update at 13 years. <span><span class="ref-journal">Transplantation. </span>2003 Sep 15;<span class="ref-vol">76</span>(5):827-32.</span> [<a href="/pmc/articles/PMC2975613/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2975613</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14501862" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14501862</span></a>]</div></dd><dt>40.</dt><dd><div class="bk_ref" id="article-169702.r40">Nakai T, Honda N, Soga E, Fukui S, Kitada A, Yokogawa N, Okada M. A retrospective analysis of the safety of tacrolimus use and its optimal cut-off concentration during pregnancy in women with systemic lupus erythematosus: study from two Japanese tertiary referral centers. <span><span class="ref-journal">Arthritis Res Ther. </span>2024 Jan 04;<span class="ref-vol">26</span>(1):15.</span> [<a href="/pmc/articles/PMC10765865/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10765865</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/38178242" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 38178242</span></a>]</div></dd><dt>41.</dt><dd><div class="bk_ref" id="article-169702.r41">Nevers W, Pupco A, Koren G, Bozzo P. Safety of tacrolimus in pregnancy. <span><span class="ref-journal">Can Fam Physician. </span>2014 Oct;<span class="ref-vol">60</span>(10):905-6.</span> [<a href="/pmc/articles/PMC4196812/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4196812</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25316742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25316742</span></a>]</div></dd><dt>42.</dt><dd><div class="bk_ref" id="article-169702.r42">Li R, Zhang C, Wang H, An Y. Breastfeeding by a mother taking cyclosporine for nephrotic syndrome. <span><span class="ref-journal">Int Breastfeed J. </span>2022 Oct 17;<span class="ref-vol">17</span>(1):72.</span> [<a href="/pmc/articles/PMC9578242/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9578242</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36253832" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36253832</span></a>]</div></dd><dt>43.</dt><dd><div class="bk_ref" id="article-169702.r43">Kociszewska-Najman B, Mazanowska N, Borek-Dzięcioł B, Pączek L, Samborowska E, Szpotańska-Sikorska M, Pietrzak B, Dadlez M, Wielgoś M. Low Content of Cyclosporine A and Its Metabolites in the Colostrum of Post-Transplant Mothers. <span><span class="ref-journal">Nutrients. </span>2020 Sep 04;<span class="ref-vol">12</span>(9)</span> [<a href="/pmc/articles/PMC7551077/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7551077</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32899873" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32899873</span></a>]</div></dd></dl></div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_top_margin">
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<b>Disclosure: </b>Mugdha Kulkarni declares no relevant financial relationships with ineligible companies.</p></div></dd><dt></dt><dd><div><p class="no_top_margin">
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<b>Disclosure: </b>Sayna Norouzi declares no relevant financial relationships with ineligible companies.</p></div></dd><dt></dt><dd><div><p class="no_top_margin">
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<b>Disclosure: </b>Mohamed Hassanein declares no relevant financial relationships with ineligible companies.</p></div></dd><dt></dt><dd><div><p class="no_top_margin">
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<b>Disclosure: </b>Silvi Shah declares no relevant financial relationships with ineligible companies.</p></div></dd></dl></div></div></div>
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