Minimal Change Disease Complicated by IgG4-related Kidney DiseaseDeveloping Acute Kidney Injury: A Case Report and Literature Review

Minimal Change Disease Complicated by IgG4-related Kidney DiseaseDeveloping Acute Kidney Injury: A Case Report and Literature Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Minimal Change Disease Complicated by IgG4-related Kidney DiseaseDeveloping Acute Kidney Injury: A Case Report and Literature Review Shun Ishigaki, Yuji Oe, Shun Watanabe, Sawako Goto, Koichi Kikuchi, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7788772/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jan, 2026 Read the published version in Renal Replacement Therapy → Version 1 posted You are reading this latest preprint version Abstract The coexistence of IgG4-related kidney disease (IgG4-RKD) and minimal change disease (MCD) is extremely rare. A 60-year-old woman with bilateral submandibular gland swelling and high serum IgG4 levels was admitted to our hospital because of massive proteinuria. Renal biopsy revealed MCD concurrent with IgG4-related tubulointerstitial nephritis. She rapidly developed acute kidney injury requiring transient hemodialysis. Subsequently, her renal function and proteinuria improved with immunosuppressive therapy using prednisolone and cyclosporine, achieving partial remission This case highlights the diverse manifestations of IgG4-related kidney disease and suggests that the coexistence of two renal disorders may contribute to disease severity. Figures Figure 1 Figure 2 Figure 3 Introduction IgG4-related disease is a clinical entity characterized by elevated serum IgG4 levels and tumor-like lesions or tissue infiltration by IgG4-positive plasma cells 1) . It can affect various organs, including the pancreas, lacrimal glands, salivary glands, kidneys, lungs, retroperitoneum, aorta, skin, and lymph nodes 2) . IgG4-related kidney disease (IgG4-RKD) was first reported in 2004 3) , and diagnostic criteria were proposed by the Japanese Society of Nephrology in 2011 4) . Moreover, the diagnostic criteria were revised in 2020 5) . Tubulointerstitial nephritis (TIN) is the most common lesion in IgG4-RKD, characterized by infiltration of lymphocytes and plasma cells, with an IgG4/IgG-positive plasma cell ratio greater than 40% or more than 10 cells per high-power field (HPF), and mat-like fibrosis surrounding the infiltrating cells. Nephrotic syndrome is characterized by massive proteinuria caused by increased glomerular permeability due to glomerulopathy and is accompanied by hypoalbuminemia. Minimal change disease (MCD) and membranous nephropathy (MN) are common forms of primary nephrotic syndrome 6) . These conditions are often associated with malignancies, autoimmune diseases, drugs, and infections 7)8) . MN is the most common form of nephrotic syndrome in IgG4-RKD, whereas cases of MCD are extremely rare. Here, we present a case of MCD concurrent with IgG4-RKD, which developed severe acute kidney injury (AKI) requiring hemodialysis. Case Report A 60-year-old woman with a medical history of endometriosis and uterine fibroids developed bilateral submandibular gland swelling in October of year X-1. As the swelling persisted, she was referred to our Department of Otolaryngology in June of year X. Laboratory tests showed elevated IgG (2799 mg/dL) and IgG4 (1440 mg/dL) levels. In mid-September of year X, she developed a generalized rash with pruritus and bilateral lower leg edema. She gained 5 kg over two weeks and visited our hospital in October. Urinalysis revealed proteinuria 3+, and serum albumin was 1.1 g/dL, prompting a referral to our department and hospital admission. On admission, her height was 153 cm, weight was 61.7 kg, body temperature was 36.5°C, blood pressure was 132/77 mmHg, and heart rate was 83 bpm. Bilateral submandibular gland swelling and leg edema were observed. Urinalysis showed protein 4+, 11.8 g/g creatinine (gCr), red blood cells 1–4/HPF, and N-acetyl-beta-glucosaminidase 31.2 IU/gCr. Blood tests showed a serum creatinine level of 0.73 mg/dL and an estimated glomerular filtration rate (eGFR) of 62 mL/min/1.73 m². The level of serum albumin was decreased to 1.2 g/dL. Serum IgG and IgG4 levels were markedly elevated at 2132 mg/dL and 1287 mg/dL, respectively. Serum and urine protein electrophoresis revealed no detectable M protein. Other laboratory findings are shown in Table 1 . Computed tomography revealed a small amount of pleural and abdominal fluid. The kidneys were slightly enlarged, and no lymph node enlargement was observed. A percutaneous renal biopsy was performed on day 3. Of 24 glomeruli, 4 showed global sclerosis. The remaining glomeruli exhibited minor abnormalities. Immunohistochemistry for IgG, IgA, C3c, and C3d was negative in the glomeruli. IgM and C1q were weakly positive in the mesangial areas. Tubular atrophy and interstitial fibrosis were observed in 40% of the area, along with lymphoplasmacytic infiltration. Immunostaining showed > 10 IgG4-positive plasma cells/HPF (Fig. 1). Electron microscopy revealed diffuse foot process effacement (Fig. 2). Finally, a diagnosis of MCD concurrent with IgG4-related TIN was established. On day 5, prednisolone (PSL) was initiated at a dose of 60 mg. The eGFR initially declined to 15 mL/min/1.73 m², and the urine output decreased to 150 mL/day by day 7. Diuretics were ineffective; therefore, hemodialysis was initiated for AKI on day 10. By day 31, urine output had increased and eGFR had risen to 41 mL/min/1.73 m², allowing the discontinuation of dialysis. However, massive proteinuria (> 8 g/gCr) persisted, and cyclosporine was added. By day 72, proteinuria had decreased to 2.6 g/gCr, and PSL was gradually tapered. Seven months later, the dose had was reduced to 10 mg. Urinary protein improved to 0.34 g/gCr, and eGFR was 43 mL/min/1.73 m². Her clinical course is shown in Fig. 3. Discussion We encountered a case of MCD complicated by IgG4-RKD. The patient developed AKI requiring transient hemodialysis. Immunosuppressive therapy improved renal dysfunction and massive proteinuria. The bilateral submandibular swelling also disappeared. Finally, seven months of treatment led to partial remission of the proteinuria. IgG4-RKD is typically associated with TIN. In addition, membranous nephropathy is a common glomerular lesion, reported in approximately 7–16% of cases 9)10)11) . In contrast, complications of MCD are extremely rare. To our best knowledge, only three cases have been reported in the literature 12)13)14) . All patients were in their 60s and were treated with steroids alone or in combination with cyclosporine. One patient died of necrotizing fasciitis, and the others generally responded well to immunosuppressive therapy, but two patients, including ours, did not achieve complete remission of proteinuria (Table2). MCD is associated with a relatively high AKI rate (~33%) and transient hemodialysis is commonly needed in approximately 25% of patients with AKI 15) . Although the precise mechanism of AKI development in MCD remains unclear, ischemic tubular injury secondary to endothelin-1–mediated vasoconstriction in the presence of massive proteinuria has been proposed 15) . One unique aspect of this case is that IgG4-RKD can also cause AKI through tubular damage 16) , suggesting that the superimposed condition may have contributed to both the development and severity of AKI. MCD generally responds well to steroid therapy. The Japan Nephrotic Syndrome Cohort Study (JNSCS) showed that 85% of patients with MCD achieve complete remission within 1 month and 89% within 6 months 6) . In comparison, the response to treatment in this case was delayed, with partial remission achieved approximately two months after initiation, and no complete remission was observed even after more than six months. A similar treatment course has been reported in another case as well 13) . Factors prolonging remission induction include age ≥60 years and the presence of chronic kidney disease (CKD) or AKI 17)18) . The presence of tubulointerstitial injury due to IgG4-RKD may have contributed to the delayed response to immunosuppressive therapy in our case. A common immune abnormality may be involved in the mechanisms underlying the simultaneous onset of both conditions. Both MCD and IgG4-RKD are associated with Th2 dominance in the immune system. Th2 cytokines, such as IL-4 and IL-13, are elevated in MCD and correlate with disease activity 19) . Similarly, IgG4-RKD involves Th2 and Treg activation, IgG4 and IgE overproduction, and eosinophilia 20) . In conclusion, although rare, MCD can be associated with IgG4-RKD. The coexistence of these two conditions may result in a more severe clinical course for the patient. Standard immunosuppressive therapies, such as steroids and cyclosporine, are effective. Further investigation into the shared Th2-dominant immune profiles of these diseases may contribute to the development of novel therapeutic strategies. Declarations Authors and Affiliations Department of Nephrology, Tohoku University Graduate School of Medicine, 1–1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980–8574, Japan. Corresponding author Correspondence to Shun Ishigaki. Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent for publication was obtained from the patient. Competing interests The authors declare no competing interests. Funding This study was not supported by any sponsor or funding. Author Contribution SI and YO wrote the manuscript, prepared the figures, and collected the data. SI, YO, SW, SG, KK, MY, RM, TN, TToyohara, KO, MM, TTanaka contributed to patient treatment and discussions. HS performed the pathological evaluation and interpreted the results. All authors reviewed and approved the final manuscript. Acknowledgement The authors thank Kei Kabasawa, Kiyomi Kisu, Tomoko Takahashi, and Rumiko Yamato for their technical support. Data Availability No datasets were generated or analyzed during the current study. References Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T,et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol 2012;22(1):1–14. Yamada,K, Yamamoto M, Saeki T, Mizushima I, Matsui S, Fujisawa Y, et al. New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases. Arthritis Res Ther 2017;19(1):262. Uchiyama-Tanaka Y, Mori Y, Kimura T, Sonomura K, Umemura S, Kishimoto N, et al. Acute tubulointerstitial nephritis associated with autoimmune-related pancreatitis. Am J Kidney Dis 2004;43:e18-e25. Kawano M, Saeki T, Nakashima H, Nishi S, Yamaguchi Y, Hisano S, et al. Proposal for diagnostic criteria for IgG4-related kidney disease. Clin Exp Nephrol 2011;15 (5):615–626. Saeki T, Kawano M, Nagasawa T, Ubara Y, Taniguchi Y, Yanagita M, et al. Validation of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD) 2011, and proposal of a new 2020 version. Clin Exp Nephrol 2021;25(2):99–109. Yamamoto R, Imai E, Maruyama S, Yokoyama H, Sugiyama H, Nitta K, et al. Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS). Clin Exp Nephrol 2020;24(6):526–540. Dantos M, Silva LBB, Pontes BTM, Reis MA, Lima PSN, Neto M. Membranous nephropathy. J Bras Nefrol 2023;45(2):229–243. Vivarelli M, Massella L, Ruggiero B, Emma F. Minimal Change Disease. Clin J Am Soc Nephrol 2016;12(2):332–345. Cortazar FB, Stone JH. IgG4-related disease and the kidney. Nat Rev Nephrol 2015;11(10):599–609. Raissian Y, Nasr SH, Larsen CP, Colvin RB, Smyrk TC, Takahashi N, et al. Diagnosis of IgG4-related tubulointerstitial nephritis. J Am Soc Nephrol 2011;22(7):1343–1352. Buglioni A, Jenkins SM, Nasr SH, Zhang P, Gibson IW, Alexander MP, et al. Clinicopathologic Features of IgG4-Related Kidney Disease. Kidney Int Rep 2024;9(8):2462–2473. Yamada K, Zoshima T, Ito K, Mizushima I, Hara S, Horita S, et al. A case developing minimal change disease during the course of IgG4-related disease. Mod Rheumatol 2017;27(4):712–715. Needleman A, Sheaff M, Pepper RJ, Evanset RDR. Immunoglobulin G4-related disease presenting with nephrotic syndrome due to minimal change disease: a case report. J Med Case Rep 2024;18(1):192. Tsukamoto M, Inoue T, Naoi I, Tsunashima Y, Yamanaka R, Oda T, et al. A case of IgG4-related disease complicated with minimal change nephrotic syndrome. Himeji Red Cross Hospital Journal 2017;41:18–21. (In Japanese) Meyrier A, Niaudet P. Acute kidney injury complicating nephrotic syndrome of minimal change disease. Kidney Int 2018;94(5):861–869. Chaba A, Devresse A, Audard V, Boffa JJ, Karras A, Cartery C, et al. Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease. Clin J Am Soc Nephrol 2023;18(8):1031–1040. Shinzawa M, Yamamoto R, Nagasawa Y, Oseto S, Mori D, Tomida K, et al. Age and prediction of remission and relapse of proteinuria and corticosteroid-related adverse events in adult-onset minimal-change disease: a retrospective cohort study. Clin Exp Nephrol 2013;17(6):839–847. Chen T, Lv Y, Lin F, Zhu J, et al. Acute kidney injury in adult idiopathic nephrotic syndrome. Ren Fail 2011;33(2):144–149. Pan Q, Wu J, Tao J, Chen Y, Li L, Deng Z, et al. Role of basophils in the pathogenesis of minimal change nephrotic syndrome: A literature review. Exp Ther Med 2014;8(4):1027–1031. Michailidou D, Schwartz MD, Mustelin T, Hughes GC. Allergic Aspects of IgG4-Related Disease: Implications for Pathogenesis and Therapy. Front Immunol 2021;12:693192. Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files TablesIS.docx Cite Share Download PDF Status: Published Journal Publication published 18 Jan, 2026 Read the published version in Renal Replacement Therapy → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7788772","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":539455382,"identity":"59de264d-7723-4881-86f3-5dba314f3e49","order_by":0,"name":"Shun 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1","display":"","copyAsset":false,"role":"figure","size":623109,"visible":true,"origin":"","legend":"\u003cp\u003eLight microscopic and immunohistochemical findings of renal biopsy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003eRepresentative photomicrographs of Periodic Acid–Schiff (PAS) and Periodic Acid–Methenamine silver (PAM) stains of the glomeruli. Immunohistochemical staining for IgG, IgA, IgM, C1q, C3c, and C3d.\u003cstrong\u003e B.\u003c/strong\u003e Hematoxylin-eosin (HE) stains of the tubulointerstitial area, along with immunohistochemistry for IgG4. Scale bars represent 100 µm, respectively.\u003c/p\u003e","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7788772/v1/3e8d38e1063b8317ef374ff9.jpg"},{"id":95172697,"identity":"782cafd9-c097-41d8-9aa4-a7bda1d670c0","added_by":"auto","created_at":"2025-11-05 06:40:06","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":631712,"visible":true,"origin":"","legend":"\u003cp\u003eElectron microscopic findings of the glomerulus\u003c/p\u003e\n\u003cp\u003eArrowheads indicate the lesion of podocyte foot process effacement. Scale bars represent 5.0 µm (left) and 2.0 µm (right), respectively.\u003c/p\u003e","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7788772/v1/03b4e735c71682c1a4ac0864.jpg"},{"id":95227927,"identity":"dd4f2a99-f110-4780-bdcf-7db396e623ed","added_by":"auto","created_at":"2025-11-05 16:33:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":247608,"visible":true,"origin":"","legend":"\u003cp\u003eThe clinical course of the present case\u003c/p\u003e\n\u003cp\u003ePSL, prednisolone. CyA, cyclosporine A. HD, hemodialysis. eGFR, estimated glomerular filtration rate. Alb, albumin. UP, urinary protein.\u003c/p\u003e","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7788772/v1/f23f6314a1c99970f2c279a0.jpg"},{"id":100614894,"identity":"6b5d9fb8-1f4f-450f-ab4c-caf78265d33a","added_by":"auto","created_at":"2026-01-19 17:27:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1940852,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7788772/v1/c716598a-eef4-4711-b32e-6f210da24bbb.pdf"},{"id":95172692,"identity":"04ac7194-0bf7-4f0e-8675-22ddb6af9562","added_by":"auto","created_at":"2025-11-05 06:40:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25893,"visible":true,"origin":"","legend":"","description":"","filename":"TablesIS.docx","url":"https://assets-eu.researchsquare.com/files/rs-7788772/v1/86be0ddb21c90bfeaa061d22.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Minimal Change Disease Complicated by IgG4-related Kidney DiseaseDeveloping Acute Kidney Injury: A Case Report and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIgG4-related disease is a clinical entity characterized by elevated serum IgG4 levels and tumor-like lesions or tissue infiltration by IgG4-positive plasma cells\u003csup\u003e1)\u003c/sup\u003e. It can affect various organs, including the pancreas, lacrimal glands, salivary glands, kidneys, lungs, retroperitoneum, aorta, skin, and lymph nodes\u003csup\u003e2)\u003c/sup\u003e. IgG4-related kidney disease (IgG4-RKD) was first reported in 2004\u003csup\u003e3)\u003c/sup\u003e, and diagnostic criteria were proposed by the Japanese Society of Nephrology in 2011\u003csup\u003e4)\u003c/sup\u003e. Moreover, the diagnostic criteria were revised in 2020\u003csup\u003e5)\u003c/sup\u003e. Tubulointerstitial nephritis (TIN) is the most common lesion in IgG4-RKD, characterized by infiltration of lymphocytes and plasma cells, with an IgG4/IgG-positive plasma cell ratio greater than 40% or more than 10 cells per high-power field (HPF), and mat-like fibrosis surrounding the infiltrating cells.\u003c/p\u003e\u003cp\u003eNephrotic syndrome is characterized by massive proteinuria caused by increased glomerular permeability due to glomerulopathy and is accompanied by hypoalbuminemia. Minimal change disease (MCD) and membranous nephropathy (MN) are common forms of primary nephrotic syndrome\u003csup\u003e6)\u003c/sup\u003e. These conditions are often associated with malignancies, autoimmune diseases, drugs, and infections\u003csup\u003e7)8)\u003c/sup\u003e. MN is the most common form of nephrotic syndrome in IgG4-RKD, whereas cases of MCD are extremely rare. Here, we present a case of MCD concurrent with IgG4-RKD, which developed severe acute kidney injury (AKI) requiring hemodialysis.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 60-year-old woman with a medical history of endometriosis and uterine fibroids developed bilateral submandibular gland swelling in October of year X-1. As the swelling persisted, she was referred to our Department of Otolaryngology in June of year X. Laboratory tests showed elevated IgG (2799 mg/dL) and IgG4 (1440 mg/dL) levels. In mid-September of year X, she developed a generalized rash with pruritus and bilateral lower leg edema. She gained 5 kg over two weeks and visited our hospital in October. Urinalysis revealed proteinuria 3+, and serum albumin was 1.1 g/dL, prompting a referral to our department and hospital admission.\u003c/p\u003e\u003cp\u003eOn admission, her height was 153 cm, weight was 61.7 kg, body temperature was 36.5\u0026deg;C, blood pressure was 132/77 mmHg, and heart rate was 83 bpm. Bilateral submandibular gland swelling and leg edema were observed. Urinalysis showed protein 4+, 11.8 g/g creatinine (gCr), red blood cells 1\u0026ndash;4/HPF, and N-acetyl-beta-glucosaminidase 31.2 IU/gCr. Blood tests showed a serum creatinine level of 0.73 mg/dL and an estimated glomerular filtration rate (eGFR) of 62 mL/min/1.73 m\u0026sup2;. The level of serum albumin was decreased to 1.2 g/dL. Serum IgG and IgG4 levels were markedly elevated at 2132 mg/dL and 1287 mg/dL, respectively. Serum and urine protein electrophoresis revealed no detectable M protein. Other laboratory findings are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Computed tomography revealed a small amount of pleural and abdominal fluid. The kidneys were slightly enlarged, and no lymph node enlargement was observed. A percutaneous renal biopsy was performed on day 3. Of 24 glomeruli, 4 showed global sclerosis. The remaining glomeruli exhibited minor abnormalities. Immunohistochemistry for IgG, IgA, C3c, and C3d was negative in the glomeruli. IgM and C1q were weakly positive in the mesangial areas. Tubular atrophy and interstitial fibrosis were observed in 40% of the area, along with lymphoplasmacytic infiltration. Immunostaining showed\u0026thinsp;\u0026gt;\u0026thinsp;10 IgG4-positive plasma cells/HPF (Fig.\u0026nbsp;1). Electron microscopy revealed diffuse foot process effacement (Fig.\u0026nbsp;2). Finally, a diagnosis of MCD concurrent with IgG4-related TIN was established.\u003c/p\u003e\u003cp\u003eOn day 5, prednisolone (PSL) was initiated at a dose of 60 mg. The eGFR initially declined to 15 mL/min/1.73 m\u0026sup2;, and the urine output decreased to 150 mL/day by day 7. Diuretics were ineffective; therefore, hemodialysis was initiated for AKI on day 10. By day 31, urine output had increased and eGFR had risen to 41 mL/min/1.73 m\u0026sup2;, allowing the discontinuation of dialysis. However, massive proteinuria (\u0026gt;\u0026thinsp;8 g/gCr) persisted, and cyclosporine was added. By day 72, proteinuria had decreased to 2.6 g/gCr, and PSL was gradually tapered. Seven months later, the dose had was reduced to 10 mg. Urinary protein improved to 0.34 g/gCr, and eGFR was 43 mL/min/1.73 m\u0026sup2;. Her clinical course is shown in Fig.\u0026nbsp;3.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe encountered a case of MCD complicated by IgG4-RKD. The patient developed AKI requiring transient hemodialysis. Immunosuppressive therapy improved renal dysfunction and massive proteinuria. The bilateral submandibular swelling also disappeared. Finally, seven months of treatment led to partial remission of the proteinuria.\u003c/p\u003e\n\u003cp\u003eIgG4-RKD is typically associated with TIN. In addition, membranous nephropathy is a common glomerular lesion, reported in approximately 7\u0026ndash;16% of cases\u003csup\u003e9)10)11)\u003c/sup\u003e. In contrast, complications of MCD are extremely rare. To our best knowledge, only three cases have been reported in the literature\u003csup\u003e12)13)14)\u003c/sup\u003e. All patients were in their 60s and were treated with steroids alone or in combination with cyclosporine. One patient died of necrotizing fasciitis, and the others generally responded well to immunosuppressive therapy, but two patients, including ours, did not achieve complete remission of proteinuria (Table2).\u003c/p\u003e\n\u003cp\u003eMCD is associated with a relatively high AKI rate (~33%)\u003csup\u003e\u0026nbsp;\u003c/sup\u003eand transient hemodialysis is commonly needed in approximately 25% of patients with AKI\u003csup\u003e15)\u003c/sup\u003e. Although the precise mechanism of AKI development in MCD remains unclear, ischemic tubular injury secondary to endothelin-1\u0026ndash;mediated vasoconstriction in the presence of massive proteinuria has been proposed\u003csup\u003e15)\u003c/sup\u003e. One unique aspect of this case is that IgG4-RKD can also cause AKI through tubular damage\u003csup\u003e16)\u003c/sup\u003e, suggesting that the superimposed condition may have contributed to both the development and severity of AKI.\u003c/p\u003e\n\u003cp\u003eMCD generally responds well to steroid therapy. The Japan Nephrotic Syndrome Cohort Study (JNSCS) showed that 85% of patients with MCD achieve complete remission within 1 month and 89% within 6 months\u003csup\u003e6)\u003c/sup\u003e. In comparison, the response to treatment in this case was delayed, with partial remission achieved approximately two months after initiation, and no complete remission was observed even after more than six months. A similar treatment course has been reported in another case as well\u003csup\u003e13)\u003c/sup\u003e. Factors prolonging remission induction include age \u0026ge;60 years and the presence of chronic kidney disease (CKD) or AKI\u003csup\u003e17)18)\u003c/sup\u003e. The presence of tubulointerstitial injury due to IgG4-RKD may have contributed to the delayed response to immunosuppressive therapy in our case.\u003c/p\u003e\n\u003cp\u003eA common immune abnormality may be involved in the mechanisms underlying the simultaneous onset of both conditions. Both MCD and IgG4-RKD are associated with Th2 dominance in the immune system. Th2 cytokines, such as IL-4 and IL-13, are elevated in MCD and correlate with disease activity\u003csup\u003e19)\u003c/sup\u003e. Similarly, IgG4-RKD involves Th2 and Treg activation, IgG4 and IgE overproduction, and eosinophilia\u003csup\u003e20)\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, although rare, MCD can be associated with IgG4-RKD. The coexistence of these two conditions may result in a more severe clinical course for the patient. Standard immunosuppressive therapies, such as steroids and cyclosporine, are effective. Further investigation into the shared Th2-dominant immune profiles of these diseases may contribute to the development of novel therapeutic strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eAuthors and Affiliations\u003c/h2\u003e\u003cp\u003eDepartment of Nephrology, Tohoku University Graduate School of Medicine, 1\u0026ndash;1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980\u0026ndash;8574, Japan.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003cp\u003eCorrespondence to Shun Ishigaki.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cp\u003eWritten informed consent for publication was obtained from the patient.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was not supported by any sponsor or funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSI and YO wrote the manuscript, prepared the figures, and collected the data. SI, YO, SW, SG, KK, MY, RM, TN, TToyohara, KO, MM, TTanaka contributed to patient treatment and discussions. HS performed the pathological evaluation and interpreted the results. All authors reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank Kei Kabasawa, Kiyomi Kisu, Tomoko Takahashi, and Rumiko Yamato for their technical support.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNo datasets were generated or analyzed during the current study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eUmehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T,et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol 2012;22(1):1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamada,K, Yamamoto M, Saeki T, Mizushima I, Matsui S, Fujisawa Y, et al. New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases. Arthritis Res Ther 2017;19(1):262.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUchiyama-Tanaka Y, Mori Y, Kimura T, Sonomura K, Umemura S, Kishimoto N, et al. Acute tubulointerstitial nephritis associated with autoimmune-related pancreatitis. Am J Kidney Dis 2004;43:e18-e25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKawano M, Saeki T, Nakashima H, Nishi S, Yamaguchi Y, Hisano S, et al. Proposal for diagnostic criteria for IgG4-related kidney disease. Clin Exp Nephrol 2011;15 (5):615\u0026ndash;626.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaeki T, Kawano M, Nagasawa T, Ubara Y, Taniguchi Y, Yanagita M, et al. Validation of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD) 2011, and proposal of a new 2020 version. Clin Exp Nephrol 2021;25(2):99\u0026ndash;109.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamamoto R, Imai E, Maruyama S, Yokoyama H, Sugiyama H, Nitta K, et al. Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS). Clin Exp Nephrol 2020;24(6):526\u0026ndash;540.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDantos M, Silva LBB, Pontes BTM, Reis MA, Lima PSN, Neto M. Membranous nephropathy. J Bras Nefrol 2023;45(2):229\u0026ndash;243.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVivarelli M, Massella L, Ruggiero B, Emma F. Minimal Change Disease. Clin J Am Soc Nephrol 2016;12(2):332\u0026ndash;345.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCortazar FB, Stone JH. IgG4-related disease and the kidney. Nat Rev Nephrol 2015;11(10):599\u0026ndash;609.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaissian Y, Nasr SH, Larsen CP, Colvin RB, Smyrk TC, Takahashi N, et al. Diagnosis of IgG4-related tubulointerstitial nephritis. J Am Soc Nephrol 2011;22(7):1343\u0026ndash;1352.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBuglioni A, Jenkins SM, Nasr SH, Zhang P, Gibson IW, Alexander MP, et al. Clinicopathologic Features of IgG4-Related Kidney Disease. Kidney Int Rep 2024;9(8):2462\u0026ndash;2473.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamada K, Zoshima T, Ito K, Mizushima I, Hara S, Horita S, et al. A case developing minimal change disease during the course of IgG4-related disease. Mod Rheumatol 2017;27(4):712\u0026ndash;715.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeedleman A, Sheaff M, Pepper RJ, Evanset RDR. Immunoglobulin G4-related disease presenting with nephrotic syndrome due to minimal change disease: a case report. J Med Case Rep 2024;18(1):192.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTsukamoto M, Inoue T, Naoi I, Tsunashima Y, Yamanaka R, Oda T, et al. A case of IgG4-related disease complicated with minimal change nephrotic syndrome. Himeji Red Cross Hospital Journal 2017;41:18\u0026ndash;21. (In Japanese)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMeyrier A, Niaudet P. Acute kidney injury complicating nephrotic syndrome of minimal change disease. Kidney Int 2018;94(5):861\u0026ndash;869.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChaba A, Devresse A, Audard V, Boffa JJ, Karras A, Cartery C, et al. Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease. Clin J Am Soc Nephrol 2023;18(8):1031\u0026ndash;1040.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShinzawa M, Yamamoto R, Nagasawa Y, Oseto S, Mori D, Tomida K, et al. Age and prediction of remission and relapse of proteinuria and corticosteroid-related adverse events in adult-onset minimal-change disease: a retrospective cohort study. Clin Exp Nephrol 2013;17(6):839\u0026ndash;847.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen T, Lv Y, Lin F, Zhu J, et al. Acute kidney injury in adult idiopathic nephrotic syndrome. Ren Fail 2011;33(2):144\u0026ndash;149.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePan Q, Wu J, Tao J, Chen Y, Li L, Deng Z, et al. Role of basophils in the pathogenesis of minimal change nephrotic syndrome: A literature review. Exp Ther Med 2014;8(4):1027\u0026ndash;1031.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMichailidou D, Schwartz MD, Mustelin T, Hughes GC. Allergic Aspects of IgG4-Related Disease: Implications for Pathogenesis and Therapy. Front Immunol 2021;12:693192.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7788772/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7788772/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe coexistence of IgG4-related kidney disease (IgG4-RKD) and minimal change disease (MCD) is extremely rare. A 60-year-old woman with bilateral submandibular gland swelling and high serum IgG4 levels was admitted to our hospital because of massive proteinuria. Renal biopsy revealed MCD concurrent with IgG4-related tubulointerstitial nephritis. She rapidly developed acute kidney injury requiring transient hemodialysis. Subsequently, her renal function and proteinuria improved with immunosuppressive therapy using prednisolone and cyclosporine, achieving partial remission This case highlights the diverse manifestations of IgG4-related kidney disease and suggests that the coexistence of two renal disorders may contribute to disease severity.\u003c/p\u003e","manuscriptTitle":"Minimal Change Disease Complicated by IgG4-related Kidney DiseaseDeveloping Acute Kidney Injury: A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-05 06:40:00","doi":"10.21203/rs.3.rs-7788772/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0d039102-e429-49b7-ba2a-9d1d3ea7bf11","owner":[],"postedDate":"November 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-19T16:50:17+00:00","versionOfRecord":{"articleIdentity":"rs-7788772","link":"https://doi.org/10.1186/s41100-025-00699-4","journal":{"identity":"renal-replacement-therapy","isVorOnly":false,"title":"Renal Replacement Therapy"},"publishedOn":"2026-01-18 16:31:00","publishedOnDateReadable":"January 18th, 2026"},"versionCreatedAt":"2025-11-05 06:40:00","video":"","vorDoi":"10.1186/s41100-025-00699-4","vorDoiUrl":"https://doi.org/10.1186/s41100-025-00699-4","workflowStages":[]},"version":"v1","identity":"rs-7788772","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7788772","identity":"rs-7788772","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}