- Case report
- Open access
- Published:
Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report
BMC Nephrology volume 24, Article number: 92 (2023)
Abstract
Background
Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy.
Case presentation
A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia.
Conclusion
Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.
Background
Immunoglobulin A (IgA) nephropathy is the most common type of glomerulonephritis worldwide and is characterized by mesangial deposits of IgA1, often with co-deposits of Complement component 3 (C3) [1]. It is a common disease among young people and often occurs in women of childbearing age. Patients with IgA nephropathy rarely present with nephrotic syndrome (NS). Crescentic IgA nephropathy, defined as more than 50% of the glomeruli with crescents, is rare (1.14%) and sometimes presents with nephrotic syndrome [2, 3]. Its renal survival rate is only 50% at 1 year and 20% at 5 years [4]. However, the pathogenesis of crescent formation in IgA nephropathy remains unclear. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and aggravation of subclinical nephropathies [5].
Herein, we report a case of nephrotic syndrome due to crescentic IgA nephropathy, possibly triggered by pregnancy. To the best of our knowledge, it has not been reported that pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.
Case report
A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. Her serum creatinine (sCr) level was 0.43 mg/dL, with no proteinuria and hematuria observed before pregnancy. She was diagnosed with proteinuria for the first time at 36 weeks of gestation. Her sCr levels were 0.45 mg/dL and 0.61 mg/dL at 37 and 38 weeks of gestation, respectively. There were no signs of infection immediately prior to the onset of proteinuria. She was normotensive with no symptoms such as swelling, headaches, upper abdominal pain, or shortness of breath before and after 36 weeks. Further, she showed no signs of cytomegalovirus or chlamydia infection during pregnancy. She had no significant medical history, allergies, or medications. There were no problems with her previous pregnancy. At 38 weeks, labor was induced, and she delivered a 3,290 g male infant. She presented with extensive peripheral edema on her first visit. She did not present with purpura, arthralgia, or abdominal pain. The laboratory findings on her first visit at two months postpartum are summarized in Table 1. Urinalysis revealed proteinuria (7.39 g/gCr) and hematuria (sediment red blood cells > 100 per high-power field). Urinary excretion of beta2-microglobulin (MG) and N-acetyl-beta-D-glycosaminidase were markedly elevated (1079 µg/mL and 90.1 U/L, respectively). Her sCr level was normal (0.70 mg/dL). She had low serum total protein and albumin levels of 5.3 g/dL and 2.2 g/dL, respectively. Based on these results, the patient was diagnosed with nephrotic syndrome. The antinuclear antibody titer was 1:160. She also tested negative for anti-DNA, IgG anticardiolipin antibodies, myeloperoxidase anti-neutrophil cytoplasmic, proteinase 3 anti-neutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane (anti-GBM), and anti-Smith antibodies. Serum protein electrophoresis revealed no monoclonal spikes. Renal ultrasound showed that the kidneys were normal in size (right, 108 × 51 mm; left, 110 × 55 mm) without dilation of the urinary tract, renal pelvis, or calyces. The corticomedullary junction was obscured. The renal arterial resistive index was normal (right, 0.50; left, 0.51). A renal biopsy was performed because the urinary protein persisted until 4 months postpartum. There were 35 glomeruli with no global sclerotic glomeruli. Diffuse and moderate mesangial proliferation and crescent formation were also observed. Crescent formation (28 cellular and one fibro-cellular) was observed in 29 of 35 glomeruli (Fig. 1a and Supplementary Fig). Endotheliosis was not observed in the glomeruli. No fibrinoid necrosis was observed in the glomeruli or arteries. IgA immunofluorescence staining showed a strong granular pattern for IgA (Fig. 1b) associated with IgG, IgM, and C3 (Fig. 1c) and fibrinogen levels in the mesangium. C1q and C4 levels were negative. Interstitial fibrosis and tubular atrophy were not observed. Electron microscopy showed electron-dense deposits, mainly in the mesangial area (Fig. 1d). Based on these findings, the patient was diagnosed with crescentic IgA nephropathy (M1E1S1T0C2 according to the Oxford Classification [6]). The clinical course of the patient is shown in Fig. 2. She was treated with methylprednisolone (mPSL) pulse therapy, followed by conventional prednisolone therapy. A tonsillectomy was performed 10 months postpartum. Both proteinuria and serum albumin levels gradually improved (0.89 g and 4.1 mg/dL, respectively), as well as hematuria at 16 months postpartum.
Discussion and conclusions
We report a rare case of nephrotic syndrome in a 33-year-old multipara that might be attributed to pregnancy-related crescentic IgA nephropathy. There has been insufficient data regarding the new onset of glomerulonephritis or aggravation of subclinical nephropathies in the course of gestation [5]. Although the precise mechanisms remain unclear, we assume that crescentic IgA nephropathy is related to pregnancy for two reasons. First, no urinary abnormalities were observed before 36 weeks of gestation. Second, renal biopsy revealed that most crescents were cellular, with no global sclerosis. These findings suggest a relatively new-onset crescentic IgA nephropathy during pregnancy. Excessive complement activation may be involved in crescent formation, and complement inhibition with the humanized anti-C5 monoclonal antibody eculizumab may be beneficial for crescentic IgA nephropathy [7, 8]. In general, complement activation may play a key role in placental formation and pregnancy maintenance [9]. It is possible that crescentic IgA nephropathy is related to pregnancy through complement activation. In this case, plasma C3, C4, and CH50 levels were normal. However, further complements, including factor H, factor B, C1q, mannose-binding lectin, C3c, C3a, C5a, and soluble C5b-9 have not been analyzed. Further studies are needed to assess whether pregnancy induces crescentic IgA nephropathy through complement activation. Crescent glomerulonephritis includes pauci-immune, immune-complex-mediated, and anti-glomerular basement membrane diseases. Macrophage inflammatory protein-1α may be involved in the development of cellular crescents in crescentic glomerulonephritis [10]. In this case, there was no fibrinoid necrosis in the glomeruli and small arteries, and ANCA and anti-GBM antibody data were negative. Therefore, ANCA-associated vasculitis and anti-GBM diseases are less likely. IgA nephropathy is an immune-complex-mediated glomerulonephritis that is recognized as an autoimmune renal disease due to increased circulating levels of IgA1 with galactose-deficient hinge region O-glycans and antiglycan autoantibodies [11]. There are some reports of Henoch-Schonlein purpura (HSP) during pregnancy [12, 13]. In this case, the possibility of HSP was low because of the absence of purpura, arthralgia, and abdominal pain. HSP and IgA nephropathy are considered related diseases resulting from the glomerular deposition of aberrantly glycosylated IgA1 [14]. There are a number of parameters other than the complement that could be altered due to pregnancy, including the gut microbiota [15], which might affect levels of IgA1 glycosylation, and the galactose-deficient IgA1 immune complex. Although the effects of pregnancy on the course of HSP and IgA nephropathy remain unclear, a similar mechanism may be involved, and further research is needed. Secondary forms of IgA nephropathy have been reported [16] and include gastrointestinal and liver disorders, infections, autoimmune disorders, and neoplasia [16]. Although we could not differentiate all diseases, our findings indicated that secondary IgA nephropathy was less likely. Pre-eclampsia is the most frequent renal complication of pregnancy and is characterized by hypertension and proteinuria after 20 weeks of gestation. Pre-eclampsia is characterized by glomerular capillary endotheliosis [17], and some patients do not have hypertension [18]. The rate of pre-existing renal disease in preeclamptic women was 71%, including IgA nephropathy (approximately 40%) [5]. It is difficult to distinguish between preexisting IgA nephropathy and preeclampsia during late pregnancy. In this report, the patient was normotensive before, during, or after pregnancy with no glomerular capillary endotheliosis. She had no organ symptoms, such as cerebrovascular events, hepatic failure, or HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) before or after 36 weeks. In addition, the presence of hematuria is not typical of preeclampsia [19]. Although the pathogenic role of many immunologic changes occurring during pregnancy remains unclear, we assume that pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy. In the present case, according to the International IgA nephropathy Prediction Tool [20], the risk of a 50% decline in estimated GFR or progression to end-stage renal disease 2 years after the landmark time post biopsy was 39.0%. Thus, it could be proposed that early diagnosis and treatment of crescentic IgA nephropathy, including pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, were crucial to achieve recovery from nephrotic syndrome and maintain renal function. In conclusion, this report describes an intriguing case in which pregnancy may trigger a new onset of crescentic IgA nephropathy or aggravation of subclinical IgA nephropathy.
Availability of data and materials
All data generated and analyzed during this study were included in this published article.
Abbreviations
- IgA:
-
Immunoglobulin A
- C3:
-
Complement component 3
- NS:
-
Nephrotic syndrome
- sCr:
-
Serum creatinine;
- MG:
-
Micro-globulin
- IgG:
-
Immunoglobulin G
- ANCA:
-
Anti-neutrophil cytoplasmic antibodies
- GBM:
-
Glomerular basement membrane
- IgM:
-
Immunoglobulin M
- C4:
-
Complement component 4
- mPSL:
-
Methylprednisolone
- C5:
-
Complement component 5
- CH50:
-
50% Hemolytic complement
- C1q:
-
Complement component 1q
- C3c:
-
Complement component 3c
- C3a:
-
Complement component 3a
- C5a:
-
Complement component 5a
- HSP:
-
Henoch-Schonlein purpura
References
Pattrapornpisut P, Avila-Casado C, Reich HN. IgA Nephropathy: Core Curriculum 2021. Am J Kidney Dis. 2021;78(3):429–41.
Tang Z, Wu Y, Wang QW, Yu YS, Hu WX, Yao XD, et al. Idiopathic IgA nephropathy with diffuse crescent formation. Am J Nephrol. 2002;22(5–6):480–6.
Herlitz LC, Bomback AS, Stokes MB, Radhakrishnan J, D’Agati VD, Markowitz GS. IgA nephropathy with minimal change disease. Clin J Am Soc Nephrol. 2014;9(6):1033–9.
Barratt J, Feehally J. Treatment of IgA nephropathy. Kidney Int. 2006;69(11):1934–8.
Unverdi S, Ceri M, Unverdi H, Yilmaz R, Akcay A, Duranay M. Postpartum persistent proteinuria after preeclampsia: a single-center experience. Wien Klin Wochenschr. 2013;125(3–4):91–5.
Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, et al. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017;91:1014–21.
Ring T, Pedersen BB, Salkus G, Goodship TH. Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum? Clin Kidney J. 2015;8(5):489–91.
Wang Z, Xie X, Li J, Zhang X, He J, Wang M, et al. Complement Activation Is Associated With Crescents in IgA Nephropathy. Front Immunol. 2021;12:676919.
He YD, Xu BN, Song D, Wang YQ, Yu F, Chen Q, et al. Normal range of complement components during pregnancy: A prospective study. Am J Reprod Immunol. 2020;83(2):e13202.
Wada T, Furuichi K, Segawa-Takaeda C, Shimizu M, Sakai N, Takeda SI, et al. MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis. Kidney Int. 1999;56(3):995–1003.
Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011;22(10):1795–803.
Koizumi M, Hagino D, Fukuyama C, Abe K, Inoue K, Arai Y, et al. Schönlein-Henoch purpura during pregnancy: Case report and review of the literature. J Obstet Gynaecol Res. 2004;30(1):37–41.
Nagai K, Kishi J, Morizumi S, Minakuchi J, Bando Y, Nishioka Y, et al. Henoch-Schonlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome. Mod Rheumatol. 2017;27(5):910–3.
Davin JC, Ten Berge IJ, Weening JJ. What is the difference between IgA nephropathy and Henoch-Schonlein purpura nephritis? Kidney Int. 2001;59(3):823–34.
Gorczyca K, Obuchowska A, Kimber-Trojnar Z, Wierzchowska-Opoka M, Leszczynska-Gorzelak B. Changes in the Gut Microbiome and Pathologies in Pregnancy. Int J Environ Res Public Health. 2022;19(16):9961.
Pouria S, Barratt J. Secondary IgA nephropathy. Semin Nephrol. 2008;28:27–37.
Karumanchi SA, Maynard SE, Stillman IE, Epstein FH, Sukhatme VP. Preeclampsia: a renal perspective. Kidney Int. 2005;67(6):2101–13.
Koizumi M, Yahata K, Ohno S, Koga K, Kikuchi Y, Hasegawa C, et al. Glomerular endotheliosis in a pregnant woman with severe gestational proteinuria. Intern Med. 2013;52(17):1943–7.
Smyth A, Wall CA. Nephrotic syndrome due to focal segmental glomerulosclerosis occurring in early pregnancy. Obstet Med. 2011;4(2):80–2.
Barbour SJ, Coppo R, Zhang H, Liu ZH, Suzuki Y, Matsuzaki K, et al. Evaluating a New International Risk-Prediction Tool in IgA Nephropathy. JAMA Intern Med. 2019;179:942–52.
Acknowledgements
We would like to thank Takatoshi Sogawa (Sogawa Women’s Clinic) for his aid with the provision of laboratory data. We would also like to thank Editage for their technical assistance in editing a draft of this manuscript.
Funding
The study was not supported by any funding sources.
Author information
Authors and Affiliations
Contributions
HS drafted the manuscript and managed the patient. HS, TI, and MT performed the renal biopsies. HS, TD, TO, TI, MT, SW, and KK performed literature searches. TD, TO, SW, KK, KO, and JM coordinated data analysis and critically commented on the manuscript. TD, TO, TI, MT, KK, KO, and JM supported the interpretation of the pathological examinations. TD, SW, KK, and JM helped write the manuscript. All the authors participated in discussions, read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable as this is a case report.
Consent for publication
A written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written informed consent form is available for review by the editor of this journal.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Additional file 1: Supplementary Figure.
Representative renal histological images of Periodic acid-Schiff staining (400× magnification). Scale bars, 50 µm.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Shima, H., Doi, T., Okamoto, T. et al. Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report. BMC Nephrol 24, 92 (2023). https://doi.org/10.1186/s12882-023-03152-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12882-023-03152-y