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Tang J, Wang L, Zhou W, Mao Y, Zhang C, Shen J, Yin M, Yin L. IgA nephropathy and IgA vasculitis in a pediatric Crohn's disease patient with early IgA deposition in vascular walls of intestines. CEN Case Rep 2025; 14:335-344. [PMID: 40011366 DOI: 10.1007/s13730-025-00970-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 01/07/2025] [Indexed: 02/28/2025] Open
Abstract
Patients with inflammatory bowel disease may present with extraintestinal manifestations. Crohn's disease complicated with IgA nephropathy or IgA vasculitis is relatively rare. In this case, an 11-year-old girl was diagnosed with Crohn's disease and infliximab was administered. 1 year after treatment, she presented with asymptomatic but persistent microscopic hematuria. The child was diagnosed with IgA vasculitis and IgA nephropathy at the fourth year of follow-up. To explore the association between Crohn's disease and IgA associated diseases, immunostaining for IgA and GdIgA1 deposition was retrospectively conducted in intestinal biopsy tissues obtained at the time of initiation and relapse of Crohn's disease. GdIgA1 deposition in intestinal tissues was found not only at the time of relapse of Crohn's disease, but also at the beginning of Crohn's disease when patient had neither exposure to any drug nor any symptom of IgA vasculitis or IgA nephropathy. The early appearance of GdIgA1 deposition indicated that Crohn's disease played a greater role in its formation than infliximab induction and the child might be prone to IgA associated diseases. Patients with Crohn's disease, especially those who receive tumor necrosis factor-alpha inhibitors are recommended to receive regular kidney examinations.
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Affiliation(s)
- Junqian Tang
- Department of Hematology/Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China
| | - Lan Wang
- Department of Gastroenterology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China
| | - Wei Zhou
- Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China
| | - Youying Mao
- Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China
| | - Chenxing Zhang
- Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China
| | - Jiayao Shen
- Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China
| | - Minzhi Yin
- Department of Pathology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.
| | - Lei Yin
- Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.
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Yang Z, Xu X, Dong Y, Wu K, Zhao S, Zhang Y. Crohn's disease-associated IgA nephropathy may prone to better renal outcome. Int Urol Nephrol 2024; 56:3815-3824. [PMID: 38904865 DOI: 10.1007/s11255-024-04106-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 05/03/2024] [Indexed: 06/22/2024]
Abstract
BACKGROUND AND AIM Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN). METHODS Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study. RESULTS Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m2 vs. 104.53 ± 32.97 ml per min per 1.73m2, p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments. CONCLUSIONS CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN.
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Affiliation(s)
- Zhihui Yang
- The Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Biomedical Innovation Center, Guangzhou, Guangdong, China
| | - Xiaochang Xu
- The Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Biomedical Innovation Center, Guangzhou, Guangdong, China
| | - Yejing Dong
- The Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Biomedical Innovation Center, Guangzhou, Guangdong, China
| | - Keping Wu
- The Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Biomedical Innovation Center, Guangzhou, Guangdong, China
| | - Shuping Zhao
- The Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Biomedical Innovation Center, Guangzhou, Guangdong, China
| | - Yimin Zhang
- The Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Biomedical Innovation Center, Guangzhou, Guangdong, China.
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Dogahe D, Taghavi M, Cubilier E, Sanoussi S, Duttman R, Nortier J, do Carmo Filomena Mesquita M. Multiple Complications of Crohn's Disease and the Need for Early and Continuous Multidisciplinary Undertaking. J Med Cases 2023; 14:356-361. [PMID: 38029055 PMCID: PMC10681768 DOI: 10.14740/jmc4154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 10/13/2023] [Indexed: 12/01/2023] Open
Abstract
Crohn's disease is an inflammatory disease that typically affects the bowels but can also have many different extraintestinal manifestations. One of those complications is immunoglobulin A nephropathy (IgAN), which is one of the most encountered renal lesions in the setting of Crohn's disease. Another point of focus for Crohn's patients is the risk of cancer, with a higher risk of colorectal cancer but also extraintestinal neoplasia such as hepatobiliary, hematological, and urinary tract neoplasia. We present the case of a young patient suffering from long-term Crohn's disease and subsequent IgAN leading to end-stage kidney disease and hemodialysis. The patient was diagnosed young and had undergone multiple surgeries and different treatments in various countries. He then presented in our center already with advanced chronic renal failure from IgAN that was unknown due to poor multidisciplinary follow-up. Shortly after starting hemodialysis, he developed a large abdominal mass, first thought to result from Crohn's-related fistula. This mass turned out to be a urachal adenocarcinoma, a rare type of bladder cancer with an especially poor prognosis. It is not known whether this type of cancer is associated with either Crohn's disease or IgAN, and no such association has been previously described. The treatment of urachal cancer usually relies on surgery, with the addition of chemotherapy in some cases. Unfortunately for our patient, his case was already so advanced at the moment of diagnosis that he was excluded from curative treatment and quickly passed away thereafter. This case illustrates many important aspects of the rigorous follow-up that is needed for Crohn's patients, with regular check-ups, screening investigations, and the need for multidisciplinary evaluation. Furthermore, it describes the development of a rare type of cancer in the setting of Crohn's disease and IgAN, with no prior established link between these different pathologies.
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Affiliation(s)
- David Dogahe
- Nephrology and Dialysis Department, Brugmann University Hospital, Universite Libre de Bruxelles (ULB), Brussels, Belgium
- These authors contributed equally to this article
| | - Maxime Taghavi
- Nephrology and Dialysis Department, Brugmann University Hospital, Universite Libre de Bruxelles (ULB), Brussels, Belgium
- These authors contributed equally to this article
| | - Edouard Cubilier
- Nephrology and Dialysis Department, Brugmann University Hospital, Universite Libre de Bruxelles (ULB), Brussels, Belgium
| | - Said Sanoussi
- Radiology Department, Brugmann University Hospital, Universite Libre de Bruxelles (ULB), Brussels, Belgium
| | - Ruth Duttman
- Pathology Department, Brugmann University Hospital, Universite Libre de Bruxelles (ULB), Brussels, Belgium
| | - Joelle Nortier
- Nephrology and Dialysis Department, Brugmann University Hospital, Universite Libre de Bruxelles (ULB), Brussels, Belgium
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Lian X, Wang Y, Wang S, Peng X, Wang Y, Huang Y, Chen W. Does inflammatory bowel disease promote kidney diseases: a mendelian randomization study with populations of European ancestry. BMC Med Genomics 2023; 16:225. [PMID: 37752523 PMCID: PMC10521387 DOI: 10.1186/s12920-023-01644-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 08/23/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND This study aimed to investigate a causal relationship between IBD and multiple kidney diseases using two-sample Mendelian randomization (MR) analyses. METHODS We selected a group of single nucleotide polymorphisms (SNPs) specific to IBD as instrumental variables from a published genome-wide association study (GWAS) with 86,640 individuals of European ancestry. Summary statistics for multiple kidney diseases were obtained from the publicly available GWAS. Genetic data from one GWAS involving 210 extensive T-cell traits was used to estimate the mediating effect on specific kidney disease. Inverse-variance weighted method were used to evaluate the MR estimates for primary analysis. RESULTS Genetic predisposition to IBD was associated with higher risk of IgA nephropathy (IgAN) (OR, 1.78; 95% CI, 1.45-2.19), but not membranous nephropathy, diabetic nephropathy, glomerulonephritis, nephrotic syndrome, chronic kidney disease, and urolithiasis. CD4 expression on CD4 + T cell had a significant genetic association with the risk of IgAN (OR, 2.72; 95% CI, 1.10-6.72). Additionally, consistent results were also observed when IBD was subclassified as ulcerative colitis (OR, 1.38; 95% CI, 1.10-1.71) and Crohn's disease (OR, 1.37; 95% CI, 1.12-1.68). MR-PRESSO and the MR-Egger intercept did not identify pleiotropic SNPs. CONCLUSIONS This study provides genetic evidence supporting a positive casual association between IBD, including its subclassification as ulcerative colitis and Crohn's disease, and the risk of IgAN. However, no casual association was found between IBD and other types of kidney diseases. Further exploration of IBD interventions as potential preventive measures for IgAN is warranted.
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Affiliation(s)
- Xingji Lian
- Department of Nephrology, The First Affiliated Hospital, NHC Key Laboratory of Nephrology (Sun Yat-sen University), Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-sen University, Guangzhou, 510080, China
- Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, National Key Clinic Specialty, South China University of Technology, Guangzhou, 510180, China
| | - Yiqin Wang
- Department of Nephrology, The First Affiliated Hospital, NHC Key Laboratory of Nephrology (Sun Yat-sen University), Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-sen University, Guangzhou, 510080, China
| | - Shuyi Wang
- Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Xiaohui Peng
- Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, National Key Clinic Specialty, South China University of Technology, Guangzhou, 510180, China
| | - Yanhui Wang
- Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, National Key Clinic Specialty, South China University of Technology, Guangzhou, 510180, China
| | - Yuyu Huang
- Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, National Key Clinic Specialty, South China University of Technology, Guangzhou, 510180, China
| | - Wei Chen
- Department of Nephrology, The First Affiliated Hospital, NHC Key Laboratory of Nephrology (Sun Yat-sen University), Guangdong Provincial Key Laboratory of Nephrology, Sun Yat-sen University, Guangzhou, 510080, China.
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Tamura H. IgA nephropathy associated with Crohn's disease. World J Methodol 2023; 13:67-78. [PMID: 37456980 PMCID: PMC10348078 DOI: 10.5662/wjm.v13.i3.67] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/16/2023] [Accepted: 05/12/2023] [Indexed: 06/20/2023] Open
Abstract
The relationship between IgA nephropathy (IgAN) and Crohn’s disease was reported. IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure, and up to 50% of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis. However, specific and effective therapeutic strategies are still lacking. In this review, we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies. Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved, the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.
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Affiliation(s)
- Hiroshi Tamura
- Department of Pediatrics, Kumamoto University, Kumamoto 8608556, Japan
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Zhang Q, Li H, Huang WF. When Crohn's disease meets IgA nephropathy: What do you think? Am J Med Sci 2023; 365:e78-e79. [PMID: 36574819 DOI: 10.1016/j.amjms.2022.12.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 09/16/2022] [Accepted: 12/16/2022] [Indexed: 12/25/2022]
Affiliation(s)
- Qi Zhang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Hua Li
- Department of Gastroenterology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Wei-Feng Huang
- Department of Gastroenterology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
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Tota M, Baron V, Musial K, Derrough B, Konieczny A, Krajewska M, Turkmen K, Kusztal M. Secondary IgA Nephropathy and IgA-Associated Nephropathy: A Systematic Review of Case Reports. J Clin Med 2023; 12:jcm12072726. [PMID: 37048809 PMCID: PMC10094848 DOI: 10.3390/jcm12072726] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/20/2023] [Accepted: 03/29/2023] [Indexed: 04/08/2023] Open
Abstract
Primary (pIgAN), secondary IgA nephropathy (sIgAN), and IgA-associated nephropathy can be distinguished. While pIgAN has been thoroughly studied, information about the etiology of sIgAN remains scarce. As concerns sIgAN, several studies suggest that different etiologic factors play a role and ultimately lead to a pathophysiologic process similar to that of pIgAN. In this article, we review a vast number of cases in order to determine the novel putative underlying diseases of sIgAN. Moreover, updates on the common pathophysiology of primary disorders and sIgAN are presented. We identified liver, gastrointestinal, oncological, dermatological, autoimmune, and respiratory diseases, as well as infectious, iatrogenic, and environmental factors, as triggers of sIgAN. As novel biological therapies for listed underlying diseases emerge, we suggest implementing drug-induced sIgAN as a new significant category. Clinicians should acknowledge the possibility of sIgAN progression in patients treated with TNF-α inhibitors, IL-12/IL-23-inhibitors, immune checkpoint inhibitors, CTLA-4, oral anticoagulants, thioureylene derivatives, and anti-vascular endothelial growth factor drugs.
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Affiliation(s)
- Maciej Tota
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
| | - Vanessa Baron
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
- Faculty of Dentistry, Wroclaw Medical University, 50-435 Wrocław, Poland
| | - Katie Musial
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
| | - Bouchra Derrough
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
| | - Andrzej Konieczny
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland
| | - Magdalena Krajewska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland
| | - Kultigin Turkmen
- Division of Nephrology, Department of Internal Medicine, Meram Medical Faculty, Necmettin Erbakan University, Konya 42090, Turkey
| | - Mariusz Kusztal
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland
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8
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Doumas SA, Tsironis C, Bolaji AA, Garantziotis P, Frangou E. Glomerulonephritis and inflammatory bowel disease: A tale of gut-kidney axis dysfunction. Autoimmun Rev 2023; 22:103327. [PMID: 36990134 DOI: 10.1016/j.autrev.2023.103327] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 03/22/2023] [Indexed: 03/30/2023]
Abstract
The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased over the past decades, imposing a growing socioeconomic burden on healthcare systems globally. Most of the morbidity and mortality related to IBD is typically attributed to gut inflammation and its complications; yet the disease is characterized by various extraintestinal manifestations that can be severe. Glomerulonephritis (GN) is of particular interest since a significant proportion of patients evolve into end-stage kidney disease, requiring kidney replacement therapy and associated with high morbidity and mortality. Herein, we review the GN landscape in IBD and define the clinical and pathogenic associations reported to date in the literature. Underlying pathogenic mechanisms suggest either the initiation of antigen-specific immune responses in the inflamed gut that cross react with non-intestinal sites, such as the glomerulus, or that extraintestinal manifestations are gut-independent events that occur due to an interaction between common genetic and environmental risk factors. We present data associating GN with IBD either as a bona fide extraintestinal manifestation or reporting it as an extraneous co-existing entity, involving various histological subtypes, such as focal segmental glomerulosclerosis, proliferative GN, minimal change disease, crescentic GN, but most emphatically IgA nephropathy. Supporting the pathogenic interplay between gut inflammation and intrinsic glomerular processes, enteric targeting the intestinal mucosa with budesonide reduced IgA nephropathy-mediated proteinuria. Elucidating the mechanisms at play would provide insight not only into IBD pathogenesis but also into the gut's role in the development of extraintestinal diseases, such as glomerular diseases.
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Crohn's disease may promote inflammation in IgA nephropathy: a case-control study of patients undergoing kidney biopsy. Virchows Arch 2022; 481:553-563. [PMID: 35809093 PMCID: PMC9534821 DOI: 10.1007/s00428-022-03373-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 06/06/2022] [Accepted: 06/24/2022] [Indexed: 11/02/2022]
Abstract
Intestinal immunity has been closely associated with the pathogenesis and progression of renal diseases, a relationship known as the "gut-kidney axis." To determine the association between immunoglobulin A nephropathy (IgAN) and Crohn's disease (CD), a clinico-pathological study was performed on patients who had IgAN with CD (CD-IgAN) and without CD (NOS-IgAN). We enrolled 29 patients diagnosed with IgAN via renal biopsy at the Tokyo Yamate Medical Center from 2009 to 2017. The patients were divided into CD-IgAN (n = 18) and NOS-IgAN (n = 11) and evaluated for clinical and pathological findings. IgA subclasses and galactose-deficient IgA1 (Gd-IgA1) were examined via immunohistochemistry using formalin-fixed paraffin-embedded sections from renal biopsy. Our results showed no significant difference in the extent of mesangial IgA subclasses or Gd-IgA1 deposition according to the presence or absence of CD. Pathologically, however, those with CD-IgAN had remarkably higher percentage of global glomerulosclerosis and extent of interstitial fibrosis and tubular atrophy (IF/TA) compared to those with NOS-IgAN. Moreover, the extent of macrophage infiltration in the glomerulus and interstitium was significantly higher in CD-IgAN than in NOS-IgAN. Clinically, the CD-IgAN group had significantly worse responsiveness to steroid treatment compared to the NOS-IgAN group. In conclusion, the similar immunological characteristics of deposited IgA molecules in the glomeruli between the CD-IgAN and NOS-IgAN groups might suggest their etiological similarity. However, a renal pathology showing advanced glomerular and tubulointerstitial sclerosis accompanying increased macrophage infiltration and highly resistant clinical features in patients with CD-IgAN suggests that some pathophysiological factors in CD, including abnormal intestinal immunity, may promote and activate the inflammatory process in IgAN via undetermined mechanisms.
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Graziano F, Busè M, Cassata N, Lentini VL, Citrano M. IgA nephropathy in a child: Crohn's disease-associated or adalimumab induced? Curr Med Res Opin 2022; 38:139-143. [PMID: 34866503 DOI: 10.1080/03007995.2021.2015155] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
In pediatric patients with Inflammatory Bowel Disease renal parenchymal disease is infrequent. There are only two reports about the association between IgA Nephropathy and Pediatric Crohn Disease. IgA Nephropathy is a rather uncommon complication of Tumor Necrosis Factor-alpha (TNF-α) inhibition. We describe a case of IgA Nephropathy which has arisen in a 11-year-old child 2 years after Crohn disease diagnosis, during therapy with anti-TNF-α. An ileal e jejunal Crohn disease was diagnosed at 9 years old, initially treated with prednisone, followed by biological therapy with anti-TNF-α (Adalimumab) due to severe disease activity, with gradual improvement of clinical conditions until clinical remission is achieved. Two years after the diagnosis, the child suddenly presented macroscopic hematuria. Subsequent laboratory examinations showed acute renal failure. So kidney biopsy was performed and IgA Nephropathy diagnosis was made. Adalimumab was discontinued and the child has been treated with steroids for sixth months associated with angiotensin-converting enzyme inhibitor resulted in clinical improvement over the following year and remission was maintained. To our knowledge the association of IgA Nephropathy and pediatric IBD during therapy with anti-TNF-α has never been reported. Careful monitoring of renal function, proteinuria, and autoantibodies is advised in patients treated with anti-TNF-α agents.
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Affiliation(s)
| | - Martina Busè
- UOSD Medical Genetics, Villa Sofia Cervello Hospital, Palermo, Italy
| | - Nicola Cassata
- Pediatric Unit, Villa Sofia Cervello Hospital, Palermo, Italy
| | | | - Michele Citrano
- Pediatric Unit, Villa Sofia Cervello Hospital, Palermo, Italy
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11
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Mertelj T, Smrekar N, Kojc N, Lindič J, Kovač D. IgA Nephropathy in a Patient Treated with Adalimumab. Case Rep Nephrol Dial 2021; 11:233-240. [PMID: 34595210 PMCID: PMC8436610 DOI: 10.1159/000515585] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 03/02/2021] [Indexed: 12/16/2022] Open
Abstract
Immunoglobulin A (IgA) nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by IgA deposits in the glomerular mesangium. It has a progressive nature and can eventually lead to end-stage kidney failure. It can occur as a potential side effect of treatment with tumor necrosis factor alpha antagonist that has been used for numerous chronic inflammatory conditions, such as Crohn's disease. In this study, the case of a 33-year-old man with renal dysfunction, nephrotic proteinuria, and erythrocyturia is described. He had had a history of Crohn's disease for 8 years and had been treated with adalimumab for the past 7 years. The diagnosis of IgAN was confirmed by kidney biopsy. After discontinuance of adalimumab and the induction of corticosteroid therapy, he made a remarkable recovery. Four years after the first presentation of IgAN and discontinuation of adalimumab, his renal function was normal with no proteinuria and only mild erythrocyturia.
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Affiliation(s)
- Tonja Mertelj
- Department of Internal Medicine, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - Nataša Smrekar
- Department of Gastroenterology, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - Nika Kojc
- Institute of Pathology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Jelka Lindič
- Department of Nephrology, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - Damjan Kovač
- Department of Nephrology, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia
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12
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Rehnberg J, Symreng A, Ludvigsson JF, Emilsson L. Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort Study. J Am Soc Nephrol 2021; 32:411-423. [PMID: 33177116 PMCID: PMC8054887 DOI: 10.1681/asn.2020060848] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 10/06/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Case reports suggest an association between inflammatory bowel disease, a chronic autoimmune condition linked to increased circulating IgA levels, and IgA nephropathy, the most common form of primary GN and a leading cause of ESKD. METHODS In a Swedish population-based cohort study, we compared 3963 biopsy-verified IgA nephropathy patients with 19,978 matched controls between 1974 and 2011, following up participants until 2015. Inflammatory bowel disease data and ESKD status were obtained through national medical registers. We applied Cox regression to estimate hazard ratios (HRs) for future inflammatory bowel disease in IgA nephropathy and conditional logistic regression to assess risk of earlier inflammatory bowel disease in IgA nephropathy. We also explored whether inflammatory bowel disease affects development of ESKD in IgA nephropathy. RESULTS During a median follow-up of 12.6 years, 196 (4.95%) patients with IgA nephropathy and 330 (1.65%) matched controls developed inflammatory bowel disease (adjusted HR, 3.29; 95% confidence interval [95% CI], 2.73 to 3.96). Inflammatory bowel disease also was more common before a confirmed IgA nephropathy diagnosis. Some 103 (2.53%) IgA nephropathy patients had an earlier inflammatory bowel disease diagnosis compared with 220 (1.09%) controls (odds ratio [OR], 2.37; 95% CI, 1.87 to 3.01). Both logistic regression (OR, 2.60; 95% CI, 2.02 to 3.35) and time-varying Cox regression (HR, 1.84; 95% CI, 1.33 to 2.55) demonstrated that inflammatory bowel disease was associated with increased ESKD risk in patients with IgA nephropathy. CONCLUSIONS Patients with IgA nephropathy have an increased risk of inflammatory bowel disease both before and after their nephropathy diagnosis. In addition, among patients with IgA nephropathy, comorbid inflammatory bowel disease elevates the risk of progression to ESKD.
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Affiliation(s)
- Johanna Rehnberg
- Department of Nephrology and Centre for Clinical Research, County Council of Värmland, Central Hospital Karlstad, Karlstad, Sweden,School of Medical Science, University of Örebro, Örebro, Sweden
| | - Adina Symreng
- Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F. Ludvigsson
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden,Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Louise Emilsson
- School of Medical Science, University of Örebro, Örebro, Sweden,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden,Årjäng Health Care Center and Centre for Clinical Research, County Council of Värmland, Värmland, Sweden,Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway
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13
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Joher N, Gosset C, Guerrot D, Pillebout E, Hummel A, Boffa JJ, Faguer S, Rabant M, Higgins S, Moktefi A, Delmas Y, Karras A, Lapidus N, Amiot A, Audard V, El Karoui K. IgA nephropathy in association with inflammatory bowel diseases: results from a national study and systematic literature review. Nephrol Dial Transplant 2021; 37:531-539. [PMID: 33416845 DOI: 10.1093/ndt/gfaa378] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Little is known about clinical characteristics and kidney outcome in patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in a context of inflammatory bowel disease (IBD). METHODS We conducted a retrospective multicenter study with centralized histological review, to analyze the presentation, therapeutic management and outcome of 24 patients suffering from IBD associated IgAN relative to a cohort of 134 patients with primary IgAN without IBD. RESULTS Crohn's disease and ulcerative colitis accounted for 75% and 25% of IBD-associated IgAN cases, respectively. IBD was diagnosed before IgAN in 23 cases (a mean of 9 years previously) and was considered active at IgAN onset in 23.6% of patients. Hypertension was present in 41.7% of patients. Urinary protein-to-creatinine ratio exceeded 100 mg/mmol in 70.8% of patients (mean: 254 mg/mmol). Estimated glomerular filtration rate (eGFR) exceeded 60 ml/min/1.73m2 in 13/24 patients and only one patient required dialysis. In the Oxford MEST-C classification of renal biopsies, 57% were M1, 48% E1, 76% S1, 57% T1+T2 and 38% C1+C2. Steroids were administered in 50% of cases. After a mean follow-up of 7.2 years, four patients (16.7%) had a poor kidney outcome: end-stage renal disease (n = 3) or a > 50% decrease in eGFR from initial values (n = 1). A similar evolution was observed in patients with primitive IgAN. CONCLUSIONS This first case series suggests that IBD-associated IgAN have frequent inflammatory lesions at onset and variable long-term outcome.
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Affiliation(s)
- Nizar Joher
- Département de Néphrologie et Transplantation, Centre de Référence Maladie Rare « Syndrome Néphrotique Idiopathique », Hôpital Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris AP-HP, Créteil, France.,Université Paris Est Créteil UPEC, Institut National de la Santé et de la Recherche Médicale INSERM U955, Institut Mondor de Recherche Biomédicale IMRB, Equipe 21, Créteil, France
| | - Clément Gosset
- Département de Pathologie, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris AP-HP, Paris, France
| | - Dominique Guerrot
- Département de Néphrologie, Hôpital Universitaire de Rouen, Rouen, France
| | - Evangeline Pillebout
- Département de Néphrologie, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Aurélie Hummel
- Département de Néphrologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Jean-Jacques Boffa
- Département de Néphrologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Stanislas Faguer
- Département de Néphrologie, Hôpital Rangueil, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France
| | - Marion Rabant
- Département de Pathologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Sarah Higgins
- Département de Pathologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Anissa Moktefi
- Département de Pathologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Yahsou Delmas
- Département de Néphrologie, Hôpital Universitaire de Bordeaux, Bordeaux, France
| | - Alexandre Karras
- Département de Néphrologie, Hôpital Européen Georges Pompidou, Paris, France
| | - Nathanaël Lapidus
- Département de Santé Publique, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.,Institut Pierre Louis d'Epidémiologie et de Santé Publique IPLESP, INSERM, Sorbonne Université, F75012, Paris, France
| | - Aurélien Amiot
- Département de Gastro-Entérologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Vincent Audard
- Département de Néphrologie et Transplantation, Centre de Référence Maladie Rare « Syndrome Néphrotique Idiopathique », Hôpital Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris AP-HP, Créteil, France.,Université Paris Est Créteil UPEC, Institut National de la Santé et de la Recherche Médicale INSERM U955, Institut Mondor de Recherche Biomédicale IMRB, Equipe 21, Créteil, France
| | - Khalil El Karoui
- Département de Néphrologie et Transplantation, Centre de Référence Maladie Rare « Syndrome Néphrotique Idiopathique », Hôpital Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris AP-HP, Créteil, France.,Université Paris Est Créteil UPEC, Institut National de la Santé et de la Recherche Médicale INSERM U955, Institut Mondor de Recherche Biomédicale IMRB, Equipe 21, Créteil, France
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14
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Abstract
The understanding of the pathogenesis of any disease is the key to effective and specific treatment of the disease. immunoglobulin A (IgA) nephropathy is an autoimmune disease of the kidney. Oxford MEST classification is commonly used to stratify patients according to the severity of the disease. Patients with IgA nephropathy seem to produce anti-GalNAc antibodies against a particularly defective IgA1. This immune complex deposits in the kidneys, leading to a type 3 hypersensitivity reaction which ultimately damages the kidneys. People of a certain genetic background and who experience upregulation of certain defective receptors seem to develop primary IgA nephropathy. Secondary IgA nephropathy could be due to dysbiosis of the microbiota in the gut, compromised gut immunity or other gut pathologies, pulmonary function abnormalities, or amyloidosis. Overproduction of IgA due to plasma cell dyscrasia or reduced clearance of IgA due to liver abnormalities could also be potential causes. Genes that predispose individuals to IgA nephropathy and intestinal abnormalities, such as Celiac disease, seem to overlap and these people tend to have a poorer prognosis and need to be placed on more intensive treatment regimens. IgA Vasculitis seems to be a systemic form of IgA nephropathy, whereby IgA deposits systemically and leads to multiple disease manifestations. Patients in high-risk groups could also be prophylactically screened for the disease and closely monitored by immunohistochemical methods such as an enzyme-linked immunosorbent assay (ELISA) or identified by genetic testing. Currently, the major treatment regimens involve supportive therapy or immunosuppressive therapy which has major side effects. More specific treatment methods such as monoclonal antibodies, immunoglobulin replacement therapy, or low-antigen-content diet could also be looked into as potential treatment options. Stem cell replacement, by way of bone marrow transplant and tonsillectomy, has been suggested as a treatment option in patients with indications.
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Affiliation(s)
- Jemima C Stanley
- Pathology, Zhejiang University School of Medicine, Hangzhou, CHN
| | - Hong Deng
- Pathology, Zhejiang University School of Medicine, Hangzhou, CHN
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15
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Identification of susceptibility locus shared by IgA nephropathy and inflammatory bowel disease in a Chinese Han population. J Hum Genet 2019; 65:241-249. [PMID: 31857673 DOI: 10.1038/s10038-019-0699-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 11/17/2019] [Accepted: 11/19/2019] [Indexed: 02/07/2023]
Abstract
Genome-wide association studies (GWAS) had discovered several genetic risk loci for IgA nephropathy (IgAN), where the susceptibility genes of CARD9 and HORMAD2 for IgAN were also implicated in inflammatory bowel disease (IBD), suggesting a shared genetic etiology of these two diseases. The aim of this study is to explore the common susceptibility loci between IgAN and IBD and provide evidences to elucidate the shared pathogenesis between these two autoimmune diseases. Nineteen single-nucleotide polymorphisms (SNPs) associated with IBD in Asian populations were selected through the National Human Genome Research Institute (NHGRI) GWAS Catalog, and 2078 IgAN patients and 2085 healthy individuals of Chinese Han ancestry were included in the two-stage case-control association study. Serum levels of complement factor B (CFB) and complement split product C3a were detected by enzyme-linked immunosorbent assay (ELISA). One significant shared association at rs4151657 (OR = 1.28, 95%CI = 1.13-1.45, P = 1.42 × 10-4) was discovered between these two diseases, which implicated CFB as a susceptibility gene for IgAN. Genotype-phenotype correlation analysis found significant association of the rs4151657-C allele with decreased serum C3 levels. In addition, the rs4151657-C allele was also associated with higher CFB levels and C3a levels, which suggested a certain degree of systemic complement activation in IgAN patients with the rs4151657-CT or CC genotypes. Our study identified one risk locus (CFB) shared by IgAN and IBD, and genetic variants of CFB may affect complement activation and associate with the predisposition to IgAN.
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16
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Bhagat Singh AK, Jeyaruban AS, Wilson GJ, Ranganathan D. Adalimumab-induced IgA nephropathy. BMJ Case Rep 2019; 12:12/3/e226442. [PMID: 30936328 DOI: 10.1136/bcr-2018-226442] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is the most commonly diagnosed glomerulonephritis worldwide. It is usually idiopathic and may be associated with many other diseases. Recently, biological agents including tumour necrosis factor alpha (TNFα) inhibitors have been identified as a potential cause for IgAN. We report the case of a 39-year-old woman who presented with renal dysfunction and visible haematuria. She had a background of Crohn's disease (CD) and had been on adalimumab for 4 years following a right hemicolectomy. Subsequently, she underwent a renal biopsy that demonstrated IgAN and adalimumab was ceased. Following a flare in her CD, she was commenced on infliximab, which led to remission of the IgAN and CD. This is the first case to demonstrate the occurrence of IgAN as a complication of a TNFα inhibitor (adalimumab) that remained in remission despite the commencement of a second TNFα inhibitor (infliximab).
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Affiliation(s)
- Aneesha Kaur Bhagat Singh
- Internal Medicine, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.,Faculty of Medicine, University of Queensland, Herston, Queensland, Australia
| | | | | | - Dwarakanathan Ranganathan
- Renal, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.,School of Medicine, Griffith University, Gold Coast, Queensland, Australia
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17
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Park S, Chun J, Han KD, Soh H, Choi K, Kim JH, Lee J, Lee C, Im JP, Kim JS. Increased end-stage renal disease risk in patients with inflammatory bowel disease: A nationwide population-based study. World J Gastroenterol 2018; 24:4798-4808. [PMID: 30479466 PMCID: PMC6235796 DOI: 10.3748/wjg.v24.i42.4798] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 10/17/2018] [Accepted: 10/21/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To estimate the risk of end-stage renal disease (ESRD) in patients with inflammatory bowel disease (IBD).
METHODS From January 2010 to December 2013, patients with Crohn’s disease (CD) and ulcerative colitis (UC) were identified, based on both the International Classification of Diseases, 10th revision (ICD-10) and the rare, intractable disease registration program codes from the National Health Insurance (NHI) database in South Korea. We compared 38812 patients with IBD to age- and sex-matched non-IBD controls with a ratio of 1:3. Patients newly diagnosed with ESRD were identified with the ICD-10 code.
RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79 (0.2%) patients with IBD and 166 (0.1%) controls. The incidence of ESRD in patients with IBD was 0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio (HR) = 3.03; 95% confidence interval (CI): 1.77-5.20; P < 0.001]. The incidences (per 1000 person-years) of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively (adjusted HR = 6.33; 95%CI: 2.75-14.56; P < 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups (0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01; 95%CI: 0.90-4.51; P = 0.089).
CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.
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Affiliation(s)
- Seona Park
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Jaeyoung Chun
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Kyung-Do Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Hosim Soh
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Kookhwan Choi
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Ji Hye Kim
- Department of Internal Medicine, CHA Gangnam Medical Center, CHA University, Seoul 06135, South Korea
| | - Jooyoung Lee
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 06236, South Korea
| | - Changhyun Lee
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 06236, South Korea
| | - Jong Pil Im
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
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18
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Schmit A, Bourquin V, Leung Ki EL, Moll S, André R. [Association of an Idiopathic nephrotic syndrome and Ulcerative colitis]. Presse Med 2018; 47:1019-1023. [PMID: 30343829 DOI: 10.1016/j.lpm.2018.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 08/29/2018] [Accepted: 09/17/2018] [Indexed: 11/19/2022] Open
Affiliation(s)
- Aline Schmit
- Hôpital de La Tour, service de médecine interne, Genève, Suisse
| | | | - En-Ling Leung Ki
- Hôpital de La Tour, service de gastro-entérologie, Genève, Suisse
| | - Solange Moll
- Hôpitaux universitaires de Genève, service de pathologie, Genève, Suisse
| | - Raphaël André
- Hôpital de La Tour, service de médecine interne, Genève, Suisse; Hôpitaux universitaires de Genève, service de dermatologie et vénéréologie, Genève, Suisse.
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19
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Abstract
Renal and urinary involvement has been reported to occur in 4% to 23% of inflammatory bowel disease (IBD) patients. Parenchymal renal disease is rare and most commonly affects glomerular and tubulointerstitial compartments. The most common findings on renal biopsy of IBD patients are IgA nephropathy and tubulointerstitial nephritis. Overall morbidity of IBD-related renal manifestations is significant, and there is often only a short window of injury reversibility. This, along with subtle clinical presentation, requires a high index of suspicion and routine monitoring of renal function. There are no established guidelines for the optimal screening and monitoring of renal function in IBD patients.
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