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Choi H, Yim H, Park I. Concurrent Fabry disease and IgA nephropathy in a patient with Crohn's disease: A case report. Nephrology (Carlton) 2025; 30:e14419. [PMID: 39667372 DOI: 10.1111/nep.14419] [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: 08/20/2024] [Revised: 11/14/2024] [Accepted: 12/02/2024] [Indexed: 12/14/2024]
Abstract
We present a unique case of concurrent Fabry disease (FD) and IgA nephropathy (IgAN) in a 27-year-old female with a 10-year history of Crohn's disease (CD). The patient presented to the nephrology clinic with microscopic haematuria and proteinuria on routine tests. A kidney biopsy revealed mesangial matrix widening, mesangial cell proliferation, and podocyte enlargement with prominent lacy and clear cytoplasm, as observed with haematoxylin and eosin staining. Immunofluorescence staining demonstrated diffuse immunoglobulin A deposits in the mesangium. Electron microscopy identified myelin-like figures in the cytoplasm of podocytes and electron-dense deposits in the mesangium, confirming IgAN and suggesting FD. Subsequent testing showed low alpha-galactosidase A (α-gal) enzyme activity in the patient's white blood cells, confirming the FD diagnosis. Enzyme replacement therapy was initiated following the diagnosis. To our knowledge, this is the first reported case of the coexistence of FD, IgAN, and CD in a single patient. This case highlights the importance of considering FD in patients with proteinuria, emphasising the need for comprehensive diagnostic evaluations in complex cases.
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Affiliation(s)
- Heejung Choi
- Department of Nephrology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hyunee Yim
- Department of Pathology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Inwhee Park
- Department of Nephrology, Ajou University School of Medicine, Suwon, Republic of Korea
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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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Yandian F, Caravaca-Fontán F, Herrera Hernandez LP, Soler MJ, Sethi S, Fervenza FC. Kidney Diseases Associated With Inflammatory Bowel Disease: Impact of Chronic Histologic Damage, Treatments, and Outcomes. Kidney Int Rep 2024; 9:383-394. [PMID: 38344742 PMCID: PMC10851004 DOI: 10.1016/j.ekir.2023.11.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/27/2023] [Accepted: 11/13/2023] [Indexed: 09/19/2024] Open
Abstract
INTRODUCTION Kidney disease is a well-known extraintestinal manifestation (EIM) associated with inflammatory bowel disease (IBD), with a variety of underlying etiologies. However, little is known about the overall outcomes and predictors. METHODS This is a retrospective, observational cohort study. Patients with IBD in whom a native kidney biopsy was performed at Mayo Clinic (Rochester, MN) between 1994 and 2022, were included. Demographic, clinical, and histologic characteristics of prognostic interest were collected. The main outcomes were kidney failure, disease remission, kidney function changes at last follow-up, and death. RESULTS From a total cohort of 318 patients, we selected a study group of 111 patients followed-up with at our institution (45 ulcerative colitis [UC] and 66 Crohn's disease [CD]), with a mean age of 48 ± 17 years (40% females). IgA nephropathy (IgAN), chronic interstitial nephritis (CIN), and acute interstitial nephritis (AIN) were the most common diagnoses (22%, 19%, 13%, respectively). Median estimated glomerular filtration rate (eGFR) at presentation was 30 ml/min per 1.73 m2 (interquartile range [IQR]: 17-54) and urinary protein-to-creatinine ratio [UPCR] 0.8 g/g (0.3-3.4), without differences between IBD types. During a median follow-up of 59 months (12-109), 29 patients (26%) reached kidney failure. By multivariable analysis, the main predictors of kidney failure were age (hazard ratio [HR]: 1.04; P = 0.002), baseline eGFR (HR: 0.94; P = 0.003) and histologic chronicity score (HR: 4.01; P < 0.001). Therapeutic management varied according to underlying etiology. Global survival (kidney failure + death) was significantly better in patients who achieved complete or partial remission, or stabilization or improvement of kidney function. CONCLUSION One-fourth of patients with IBD with kidney disease may reach kidney failure, and the main determinants of this outcome is age, baseline eGFR, and degree of chronicity in kidney biopsy.
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Affiliation(s)
- Federico Yandian
- Department of Nephrology, Hospital de Clínicas “Dr. Manuel Quintela”, Montevideo, Uruguay
| | - Fernando Caravaca-Fontán
- Department of Nephrology, Instituto de Investigación Hospital “12 de Octubre” (imas12), Madrid, Spain
| | | | - Maria José Soler
- Department of Nephrology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sanjeev Sethi
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
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Obrișcă B, Vornicu A, Mocanu V, Dimofte G, Andronesi A, Bobeică R, Jurubiță R, Sorohan B, Caceaune N, Ismail G. An open-label study evaluating the safety and efficacy of budesonide in patients with IgA nephropathy at high risk of progression. Sci Rep 2023; 13:20119. [PMID: 37978255 PMCID: PMC10656480 DOI: 10.1038/s41598-023-47393-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 11/13/2023] [Indexed: 11/19/2023] Open
Abstract
We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m2 and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI - 53.6 to - 12.2), - 49.7% (95% CI - 70.1 to - 29.4) and - 68.1% (95% CI - 80.6 to - 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI - 4.7 to 20.1), + 7.42% (95% CI - 7.23 to 22.1) and + 4.74% (95%CI - 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI - 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy.
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Affiliation(s)
- Bogdan Obrișcă
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania.
| | - Alexandra Vornicu
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Valentin Mocanu
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - George Dimofte
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Andreea Andronesi
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Raluca Bobeică
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Roxana Jurubiță
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Bogdan Sorohan
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Nicu Caceaune
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Gener Ismail
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
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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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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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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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Uedono H, Tsuda A, Ueno N, Natsuki Y, Nakaya R, Nishide K, Machiba Y, Fujimoto K, Nakatani S, Mori K, Emoto M. Seronegative Full-house Nephropathy with Crohn's Disease. Intern Med 2022; 61:3553-3558. [PMID: 35527024 PMCID: PMC9790786 DOI: 10.2169/internalmedicine.8820-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Lupus nephritis (LN) is a major risk factor for mortality in SLE, and glomerular "full-house" immunofluorescence staining is a well-known characteristic of LN. However, some cases of non-lupus glomerulonephritis can also present with a "full-house" immunofluorescence pattern. We recently encountered a patient with full-house nephropathy (FHN) during adalimumab administration for Crohn's disease. IgA nephropathy or idiopathic FHN was diagnosed, and treatment with steroids was started, after which there was improvement in proteinuria. The prognosis of FHN has been reported to be poor; therefore, aggressive treatment is required for such patients.
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Affiliation(s)
- Hideki Uedono
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Akihiro Tsuda
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Noriko Ueno
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Yuka Natsuki
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Rino Nakaya
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Kozo Nishide
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Yuri Machiba
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Kenta Fujimoto
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Shinya Nakatani
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Katsuhito Mori
- Department of Nephrology Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Masanori Emoto
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan
- Department of Nephrology Medicine, Osaka City University Graduate School of Medicine, Japan
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Xiao M, Ran Y, Shao J, Lei Z, Chen Y, Li Y. Causal association between inflammatory bowel disease and IgA nephropathy: A bidirectional two-sample Mendelian randomization study. Front Genet 2022; 13:1002928. [PMID: 36467999 PMCID: PMC9710718 DOI: 10.3389/fgene.2022.1002928] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/01/2022] [Indexed: 09/26/2023] Open
Abstract
Background: An association between inflammatory bowel disease (IBD) [which includes ulcerative colitis (UC) and Crohn's disease (CD)] and IgA nephropathy (IgAN) has been discovered in observational studies, but the causal relationship is still unknown. The aim of this study was to clarify the causal link between IBD (which includes UC and CD) and IgAN via a two-sample Mendelian randomization (MR) analysis. Methods: Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for analyses and were obtained from the publicly available genome-wide association study (GWAS) summary statistics. Inverse-variance weighting (IVW), Mendelian randomization-Egger (MR-Egger) regression, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and the weighted median were utilized to obtain the results. The MR-PRESSO test and MR-Egger regression were also performed to detect and correct horizontal pleiotropy. The Cochran's Q test and "leave-one-out" analysis were also conducted to assess the stability and reliability of the MR results. Results: This study found that IBD, UC, and CD all had significant positive causal effects on IgAN risk (IBD: OR = 1.58, 95% CI 1.15-2.16, p = 4.53 × 10-3; UC: OR = 1.55, 95% CI 1.14-2.11, p = 4.88 × 10-3; CD: OR = 1.57, 95% CI 1.21-2.03, p = 5.97 × 10-4). No significant horizontal pleiotropic effect was found for the causal association between IBD, UC, CD, and the risk of IgAN. Cochran's Q test identified no evidence of heterogeneity for the IV estimates. The "leave-one-out" sensitivity analysis also revealed that the MR results were robust. Conclusion: The results of this two-sample MR analysis supported that IBD, UC, and CD were causally associated with the risk of IgAN, while there was no sufficient evidence for the causal effect of IgAN on IBD, UC, or CD. Our findings provide theoretical support and a new perspective for the diagnosis and treatment of these two diseases.
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Affiliation(s)
- Mofan Xiao
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yan Ran
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jiayuan Shao
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhangni Lei
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yuling Chen
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yingchao Li
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Kumar S, Pollok R, Goldsmith D. Renal and Urological Disorders Associated With Inflammatory Bowel Disease. Inflamm Bowel Dis 2022:6658535. [PMID: 35942657 PMCID: PMC10393213 DOI: 10.1093/ibd/izac140] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Indexed: 12/15/2022]
Abstract
Renal and urinary tract complications related to inflammatory bowel disease (IBD) have been relatively understudied in the literature compared with other extraintestinal manifestations. Presentation of these renal manifestations can be subtle, and their detection is complicated by a lack of clarity regarding the optimal screening and routine monitoring of renal function in IBD patients. Urolithiasis is the most common manifestation. Penetrating Crohn's disease involving the genitourinary system as an extraintestinal complication is rare but associated with considerable morbidity. Some biologic agents used to treat IBD have been implicated in progressive renal impairment, although differentiating between drug-related side effects and deteriorating kidney function due to extraintestinal manifestations can be challenging. The most common findings on renal biopsy of IBD patients with renal injury are tubulointerstitial nephritis and IgA nephropathy, the former also being associated with drug-induced nephrotoxicity related to IBD medication. Amyloidosis, albeit rare, must be diagnosed early to reduce the chance of progression to renal failure. In this review, we evaluate the key literature relating to renal and urological involvement in IBD and emphasize the high index of suspicion required for the prompt diagnosis and treatment of these manifestations and complications, considering the potential severity and implications of acute or chronic loss of renal function. We also provide suggestions for future research priorities.
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Affiliation(s)
- Shankar Kumar
- Centre for Medical Imaging, University College London, London, UK
| | - Richard Pollok
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - David Goldsmith
- Renal and Transplantation Department, Guys and St Thomas' Hospitals NHS Foundation Trust, Great Maze Pond, London, UK
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11
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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: 4] [Impact Index Per Article: 1.3] [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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13
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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: 46] [Impact Index Per Article: 11.5] [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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14
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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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15
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Renal involvement in paediatric inflammatory bowel disease. Pediatr Nephrol 2021; 36:279-285. [PMID: 31820145 PMCID: PMC7815543 DOI: 10.1007/s00467-019-04413-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 10/16/2019] [Accepted: 10/31/2019] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease, ulcerative colitis and inflammatory bowel disease unclassified, is a chronic inflammatory disorder that predominantly affects the gastrointestinal (GI) tract and has a rising incidence in both children and adults. Symptoms are caused by inappropriate inflammatory response triggered by interaction between the environment, gut microbiome and host immune system in a genetically susceptible individual. Extranintestinal manifestations of IBD are common and can affect any body system outside the gut; they can precede or run parallel to GI inflammation. Renal involvement in IBD is uncommon and can be part of extraintestinal manifestation or metabolic complications of IBD. Many medications used to treat IBD can cause renal damage. Renal manifestation in children with IBD can range from asymptomatic biochemical abnormalities to variable stages of renal impairment with significant morbidity and even mortality burden.
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16
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IgA Nephropathy in the Setting of Anti-TNF-α Therapy for Inflammatory Bowel Disease. ACG Case Rep J 2020; 7:e00462. [PMID: 33062795 PMCID: PMC7526714 DOI: 10.14309/crj.0000000000000462] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 07/10/2020] [Indexed: 01/19/2023] Open
Abstract
Tumor necrosis factor-α (TNF-α)-inhibiting agents are a standard therapy for moderate-to-severe inflammatory bowel disease (IBD). IgA nephropathy in the setting of prolonged exposure to TNF-α inhibitors is a rare, clinically significant adverse event often overlooked by gastroenterologists but well documented in the rheumatologic literature. We present a case series of 3 patients with IBD on TNF-α inhibitors who developed biopsy-proven IgA nephropathy. Clinicians prescribing TNF-α inhibitors to patients with IBD need to be aware of this potential side effect. Therapies with alternative mechanisms of action should instead be considered.
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17
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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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18
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Wang M, Lv J, Zhang X, Chen P, Zhao M, Zhang H. Secondary IgA Nephropathy Shares the Same Immune Features With Primary IgA Nephropathy. Kidney Int Rep 2019; 5:165-172. [PMID: 32043030 PMCID: PMC7000803 DOI: 10.1016/j.ekir.2019.10.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 01/26/2023] Open
Abstract
Introduction Galactose-deficient IgA1 (Gd-IgA1) and related IgA/IgG immune complexes have been identified as the key drivers in the pathogenesis of IgA nephropathy (IgAN). However, their roles in the development of secondary IgAN are still unknown. Methods In this study, we measured the plasma Gd-IgA1 level, IgA/IgG complex, and Gd-IgA1 glomerular deposits in 100 patients with various kinds of secondary IgAN. Plasma Gd-IgA1 was measured using a lectin-based enzyme-linked immunosorbent assay, and Gd-IgA1 in glomerular deposits was examined by double immunofluorescent staining using its specific monoclonal antibody KM55. Results Patients with secondary IgAN presented with higher plasma Gd-IgA1 levels compared to healthy controls (median, 354.61 U/ml; interquartile range [IQR], 323.93, 395.57 U/ml vs. median, 303.17 U/ml; IQR, 282.24, 337.92 U/ml, P < 0.001) or patients with other kidney diseases (median, 314.61 U/ml; IQR, 278.97, 343.55 U/ml, P < 0.001). A similar trend was observed in plasma IgA/IgG immune complexes or IgA1. There were no differences between secondary and primary IgAN in plasma Gd-IgA1 levels (median, 378.54 U/ml; IQR, 315.96, 398.33 U/ml, P = 0.700) and IgA1-IgG complex levels (median, 18.76 U/ml; IQR, 14.51, 22.83 U/ml vs. median, 19.11 U/ml; IQR, 13.21, 22.37 U/ml, P = 0.888). Co-localized IgA1 and Gd-IgA1 of both secondary and primary IgAN indicated that they both share the feature of Gd-IgA1 deposits on the glomerular mesangium. Conclusion Our study strongly suggests that secondary IgAN shares a similar galactose-deficient IgA1-oriented pathogenesis with primary IgAN.
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Affiliation(s)
- Manliu Wang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Peking University Institute of Nephrology, Beijing, China.,Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.,Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.,Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Jicheng Lv
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Peking University Institute of Nephrology, Beijing, China.,Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China
| | - Xue Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Peking University Institute of Nephrology, Beijing, China.,Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China
| | - Pei Chen
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Peking University Institute of Nephrology, Beijing, China.,Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China
| | - Minghui Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Peking University Institute of Nephrology, Beijing, China.,Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.,Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.,Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Hong Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Peking University Institute of Nephrology, Beijing, China.,Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China
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19
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Pohjonen J, Nurmi R, Metso M, Oksanen P, Huhtala H, Pörsti I, Mustonen J, Kaukinen K, Mäkelä S. Inflammatory bowel disease in patients undergoing renal biopsies. Clin Kidney J 2019; 12:645-651. [PMID: 31583091 PMCID: PMC6768292 DOI: 10.1093/ckj/sfz004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There are no good data in the literature on the prevalence of inflammatory bowel disease (IBD) in patients with kidney disease and we do not know whether IBD affects the course of kidney disease or if the type of IBD is an influential factor. The aim of this study was to evaluate the prevalence of IBD among patients who have undergone renal biopsies due to clinical indications and to elucidate whether the presence of IBD influences renal and patient outcomes. METHODS We collected retrospective data on concomitant diseases, especially IBD, from adult patients undergoing renal biopsy for any clinical indication between 2000 and 2012 at Tampere University Hospital, Tampere, Finland. Information was systematically collected on the activity of IBD, medication for IBD, surgery performed for IBD and markers of kidney function. RESULTS Of the 819 patients biopsied, 35 (4.3%) had IBD. The prevalence of IBD was 13.3 and 4.6% in patients with tubulointerstitial nephritis (TIN) and immunoglobulin A nephropathy (IgAN), respectively. In comparison, the prevalence of IBD in the Finnish population is 0.6%. Ulcerative colitis and Crohn's disease were equally represented. The presence of IBD showed no impact on renal and patient outcomes. CONCLUSIONS IBD should not be overlooked in patients undergoing renal biopsies, especially those diagnosed with TIN or IgAN. The renal findings did not associate with the activity of intestinal inflammation. Whether a concomitant IBD truly affects the course of chronic kidney disease should be examined in further studies.
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Affiliation(s)
- Jussi Pohjonen
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Rakel Nurmi
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
| | - Martti Metso
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Pia Oksanen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
- Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Ilkka Pörsti
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
- Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
| | - Jukka Mustonen
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
- Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Satu Mäkelä
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
- Faculty of Medicine and Life Sciences, Tampere University, Tampere, Finland
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20
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Obrișcă B, Ștefan G, Gherghiceanu M, Mandache E, Ismail G, Stancu S, Boitan B, Ion O, Mircescu G. "Associated" or "Secondary" IgA nephropathy? An outcome analysis. PLoS One 2019; 14:e0221014. [PMID: 31398224 PMCID: PMC6688810 DOI: 10.1371/journal.pone.0221014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 07/30/2019] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Whether differences in outcome between primary (pIgAN) and secondary IgA nephropathy (sIgAN) exist is uncertain. METHODS We conducted a retrospective, observational study that included all histologically diagnosed IgAN patients between 2010-2017 (N = 306), 248 with pIgAN and 58 with sIgAN. To obtain samples with similar risk of progression, sIgAN patients were grouped as liver disease and autoimmune/viral disease and propensity score matched to corresponding pIgAN samples. Univariate (Kaplan Meier) and multivariate time-dependent (Cox modelling) analyses were performed to identify predictors of the composite end-point (doubling of serum creatinine, end-stage kidney disease or death). RESULTS Of the whole cohort, 20% had sIgAN (6% alcoholic cirrhosis, 6% autoimmune disease and 8% viral infections). sIgAN patients were older, had more comorbidities, lower proteinuria and higher haematuria, but similar distribution in MESTC lesions and eGFR as those with pIgAN. They reached the end-point in similar proportions with those with pIgAN (43 vs. 30%; p = 0.09) but their mortality was higher (19 vs. 3%; p<0.0001). Both in unmatched (HR 0.80, 95%CI 0.42-1.52; p = 0.5) and matched samples (log-rank test: liver disease-IgAN vs. pIgAN, p = 0.1; autoimmune/viral-IgAN vs. pIgAN, p = 0.3), sIgAN was not predictive for end-point. In analyses restricted only to sIgAN, those with viral infections (HR, 10.98; 95% CI, 1.12-107.41; p = 0.03) and lower eGFR (HR, 0.94; 95%CI, 0.89-0.98; p = 0.007) had a worse prognosis. Immunosuppression did not influence outcome. CONCLUSIONS The differences in MESTC score and outcome between pIgAN and sIgAN seems to be minimal, suggesting that "associated" describes better than "secondary" the relationship among the two. Immunosuppression did not to influence outcome of sIgAN.
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Affiliation(s)
- Bogdan Obrișcă
- Nephrology Department, Fundeni Clinical Institute, Bucharest, Romania
- Nephrology Department,”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | - Gabriel Ștefan
- Nephrology Department,”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- ”Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Mihaela Gherghiceanu
- Nephrology Department,”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- ”Victor Babes” National Institute of Pathology, Bucharest, Romania
| | - Eugen Mandache
- ”Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Gener Ismail
- Nephrology Department, Fundeni Clinical Institute, Bucharest, Romania
- Nephrology Department,”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | - Simona Stancu
- Nephrology Department,”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- ”Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Bianca Boitan
- ”Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Oana Ion
- Nephrology Department, Fundeni Clinical Institute, Bucharest, Romania
| | - Gabriel Mircescu
- Nephrology Department,”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- ”Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
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21
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Abstract
IgA nephropathy (IgAN) is one of the most common primary glomerulonephritides throughout the world and a major cause of end-stage renal disease among the East Asian population. It is widely considered that genetic factors play an important role in the pathogenesis of IgAN. This article summarizes the recent achievements in the genetic studies of IgAN, focusing mainly on studies performed in East Asia, from the early association studies of candidate genes and family based designs, to the recent genome-wide association studies. There have been five large genome-wide association studies performed that have identified multiple susceptibility loci for IgAN, especially some novel loci identified in the Chinese population. Genes within these loci have provided important insights into the potential biological mechanisms and pathways that influence genetic risk to IgAN. In susceptibility loci/genes, the study of genetic interaction and structural variants (such as copy number variation) was conducted to identify more variants associated with IgAN and disease progression. Genetic studies of IgAN from East Asia have made great achievements over the years. Most susceptibility loci discovered to date encode genes involved in the response to mucosal pathogens, suggesting that an intestinal-immune network for IgA production may be involved in the pathogenesis of IgAN. Although genetic studies of the complex diseases are challenging, for future genetic studies in IgAN, new genetic techniques and methods of analysis, especially next-generation sequencing, need to be applied to push the genetic studies forward.
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Affiliation(s)
- Ming Li
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.; Key Laboratory of Nephrology, National Health Commission (NHC) and Guangdong Province, Guangzhou, Guangdong, China
| | - Xue-Qing Yu
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.; Key Laboratory of Nephrology, National Health Commission (NHC) and Guangdong Province, Guangzhou, Guangdong, China.; Guangdong Medical University, Zhanjiang, Guangdong, China..
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22
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Abstract
The connection between a dysregulated gut-associated lymphoid tissue and IgA nephropathy (IgAN) was supposed decades ago after the observation of increased association of IgAN with celiac disease. Pivotal studies have shown a role for alimentary antigens, particularly gliadin in developing IgAN in BALB/c mice, and a reduction in IgA antigliadin antibodies and proteinuria was reported after gluten free-diet in patients with IgAN. Recently a genome-wide association study showed that most loci associated with IgAN also are associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier, and response to gut pathogens. Transgenic mice that overexpress the B-cell activating factor develop hyper-IgA with IgAN modulated by alimentary components and intestinal microbiota. Mice expressing human IgA1 and a soluble form of the IgA receptor (sCD89) develop IgAN, which is regulated by dietary gluten. Recent observations have confirmed gut-associated lymphoid tissue hyper-reactivity in IgAN patients with IgA against alimentary components. Interesting results were provided by the NEFIGAN randomized controlled trial, which adopted an enteric controlled-release formulation of the corticosteroid budesonide targeted to Peyer's patches. After 9 months of treatment, a reduction in proteinuria was observed with stabilized renal function and limited adverse events. The gut-renal connection is an area of promising new treatment approaches for patients with IgAN.
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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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Saha MK, Julian BA, Novak J, Rizk DV. Secondary IgA nephropathy. Kidney Int 2018; 94:674-681. [PMID: 29804660 PMCID: PMC6981247 DOI: 10.1016/j.kint.2018.02.030] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2017] [Revised: 01/24/2018] [Accepted: 02/06/2018] [Indexed: 12/14/2022]
Abstract
IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culminate in the development of primary IgA nephropathy. Whether secondary forms of the disease share common pathways triggered by underlying disorders or different mechanisms leading to similar pathologic findings remains to be determined. In this article we describe the most frequent etiologies for secondary IgA nephropathy and review the available literature for the pathophysiology.
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Affiliation(s)
- Manish K Saha
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Bruce A Julian
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jan Novak
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Dana V Rizk
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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25
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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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26
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The gut-kidney axis in IgA nephropathy: role of microbiota and diet on genetic predisposition. Pediatr Nephrol 2018; 33:53-61. [PMID: 28389744 DOI: 10.1007/s00467-017-3652-1] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 02/25/2017] [Accepted: 02/27/2017] [Indexed: 12/21/2022]
Abstract
Recent data suggest that gut-associated lymphoid tissue (GALT) plays a major role in the development of immunoglobulin A (IgA) nephropathy (IgAN). A genome-wide association study showed that most loci associated with the risk of IgAN are also associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier and regulation of response to gut pathogens. Studies involving experimental models have demonstrated a pivotal role of intestinal microbiota in the development of IgAN in mice producing high levels of IgA and in transgenic mice overexpressing BAFF, a B-cell factor crucial for IgA synthesis, indicating the role of genetic background, B-cell activity, GALT intestinal immunity and diet. The effect of diet was suggested by pilot studies carried out 30 years ago which showed that a gluten-rich diet induced IgAN in mice and that some patients benefited from a gluten-free diet. A recent experimental model in mice expressing human IgA1 and Fc alpha receptor CD89 reported clinical and histological improvement after a gluten-free diet. Clinical observations have elicited new interest in GALT hyper-reactivity in IgAN patients. In a pilot study, a reduction in proteinuria was attained using an enteric controlled-release formulation of the corticosteroid budesonide targeted to the Peyer's patches at the ileocecal junction. This formulation was tested in the placebo-controlled NEFIGAN phase 2b trial, with a reduction in proteinuria after 9 months of treatment together with stabilization of renal function in patients with persistent proteinuria. In conclusion, the gut-kidney axis modulated by microbiota and diet is a promising target for focused treatment of IgAN in genetically predisposed patients at risk of progression.
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27
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Windon AL, Shroff SG. Iatrogenic Kaposi's Sarcoma in an HIV-Negative Young Male With Crohn's Disease and IgA Nephropathy: A Case Report and Brief Review of the Literature. Int J Surg Pathol 2017; 26:276-282. [PMID: 29169276 DOI: 10.1177/1066896917736610] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Kaposi's sarcoma (KS) is a vascular tumor arising in association with human herpesvirus-8 (HHV-8) infection, and different variants show different clinical presentations. Isolated intestinal KS in the background of Crohn's disease (CD) is exceedingly rare with only 3 cases reported in the English literature (from 1966 to 2016). CASE PRESENTATION Herein, we report a case of intestinal KS in a 21-year-old HIV-negative Ethiopian male with a long-standing history of steroid therapy for his underlying IgA nephropathy. Recent gastrointestinal biopsies confirmed an additional diagnosis of CD. Despite the addition of Infliximab to his therapy, his CD remained refractory, and a laparoscopic-assisted ileocolectomy was performed to alleviate a partial small bowel obstruction. Examination of his terminal ileum demonstrated a polypoid mass with adjacent incidental ileal submucosal nodules. These nodules were composed of plump spindle cells with scattered mitoses and vascular channels with extravasated red blood cells. Intratumoral hyaline globules were also noted. Immunohistochemistry revealed HHV-8 positivity, confirming the histologic impression of KS. CONCLUSIONS Here we report the fourth case of KS in CD in an HIV-negative patient and only the third case of isolated intestinal KS in the setting of CD. A review of the literature suggests that attenuation of immunosuppressive therapy may be adequate management of iatrogenic KS in the absence of a systemic HHV-8 infection.
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Affiliation(s)
- Annika L Windon
- 1 Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Stuti G Shroff
- 1 Hospital of the University of Pennsylvania, Philadelphia, PA, USA
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Terasaka T, Uchida HA, Umebayashi R, Tsukamoto K, Tanaka K, Kitagawa M, Sugiyama H, Tanioka H, Wada J. The possible involvement of intestine-derived IgA1: a case of IgA nephropathy associated with Crohn's disease. BMC Nephrol 2016; 17:122. [PMID: 27596164 PMCID: PMC5011876 DOI: 10.1186/s12882-016-0344-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Accepted: 09/01/2016] [Indexed: 01/05/2023] Open
Abstract
Background A link between IgA nephropathy and Crohn’s disease has recently been reported. Other researchers hypothesize that intestine-derived IgA complexes deposit in glomerular mesangial cells, eliciting IgA nephropathy. Intestinal mucosal plasma cells mainly secrete IgA2. Nevertheless, IgA1 deposition is strongly implicated as being the primary cause of IgA nephropathy. Case presentation A 46-year-old Japanese man developed IgA nephropathy 29 years ago, following tonsillectomy. As a result, a normal urinalysis was obtained. The patient previously suffered Crohn’s disease followed by urinary occult blood and proteinuria six years ago. Exacerbation of IgA nephropathy was highly suspected. Therefore a renal biopsy was performed. A diagnosis of exacerbation of IgA nephropathy with mesangial cell proliferation and fibrotic cellular crescent was based upon the pathological findings. The patient exhibited a positive clinical course and eventually achieved a remission with immunosuppressive therapy including prednisolone treatment. Immunostaining for the detection of IgA subtypes was performed on both of his kidney and excised ileum. The results revealed IgA1 and IgA2 deposition by submucosal cells in intestine. Furthermore, IgA1 deposition of mesangial areas in the patient’s kidney, indicated an association of IgA1 with the exacerbation of IgA nephropathy. Conclusion This case represents the possibility that the intestine-derived IgA1 can be the origin of galactose-deficient IgA which is known to cause IgA nephropathy exacerbation.
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Affiliation(s)
- Tomohiro Terasaka
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Haruhito A Uchida
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. .,Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
| | - Ryoko Umebayashi
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Keiko Tsukamoto
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Keiko Tanaka
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Masashi Kitagawa
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Hitoshi Sugiyama
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.,Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Hiroaki Tanioka
- Department of Medicine Oncology, Okayama Rosai Hospital, 1-10-25 Chikkomidori-machi, Minami-ku, Okayama, 702-8055, Japan
| | - Jun Wada
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
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29
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The microbiota and chronic kidney diseases: a double-edged sword. Clin Transl Immunology 2016; 5:e86. [PMID: 27757226 PMCID: PMC5067952 DOI: 10.1038/cti.2016.36] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 05/11/2016] [Accepted: 05/11/2016] [Indexed: 12/11/2022] Open
Abstract
Recent findings regarding the influence of the microbiota in many inflammatory processes have provided a new way to treat diseases. Now, one may hypothesize that the origin of a plethora of diseases is related to the health of the gut microbiota and its delicate, although complex, interface with the epithelial and immune systems. The ‘westernization' of diets, for example, is associated with alterations in the gut microbiota. Such alterations have been found to correlate directly with the increased incidence of diabetes and hypertension, the main causes of chronic kidney diseases (CKDs), which, in turn, have a high estimated prevalence. Indeed, data have arisen showing that the progression of kidney diseases is strictly related to the composition of the microbiota. Alterations in the gut microbiota diversity during CKDs do not only have the potential to exacerbate renal injury but may also contribute to the development of associated comorbidities, such as cardiovascular diseases and insulin resistance. In this review, we discuss how dysbiosis through alterations in the gut barrier and the consequent activation of immune system could intensify the progression of CKD and vice versa, how CKDs can modify the gut microbiota diversity and abundance.
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31
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Recurrent IgA nephropathy complicated with Crohn's disease after renal transplantation. CEN Case Rep 2014; 3:167-171. [PMID: 28509194 DOI: 10.1007/s13730-014-0111-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Accepted: 01/28/2014] [Indexed: 10/25/2022] Open
Abstract
A 27-year-old man was diagnosed with IgA nephropathy and Crohn's disease. He had been diagnosed with proteinuria and hematuria since he was 20 years old. Diarrhea had been a continuing problem during the past 5 months. Neither corticosteroid therapy nor tonsillectomy was performed. Hemodialysis was required at age of 30, while the symptoms of Crohn's disease were ameliorated by an elemental diet. He received a renal transplant from his mother 4 months after starting dialysis therapy. The initial immunosuppression therapy consisted of methylprednisolone, mycofenolate mofetil, cyclosporine, and basiliximab. Eight months after transplantation, proteinuria and hematuria appeared and serum creatinine was 1.4 mg/dL. Relapse of IgA nephropathy was confirmed by the one-year protocol biopsy. He had suffered from tonsillitis at 32 months after the transplantation. Urinary protein increased to 3 g/day and serum creatinine was elevated to 2.04 mg/dL. Renal biopsy was performed 2 weeks after the urinary findings were aggravated. The cellular crescents constituted 36 % of the glomeruli. The findings of rejection were not confirmed in both biopsies. Tonsillectomy was performed thereafter. No additional immunosuppressive therapy was added. Proteinuria and hematuria disappeared at 4 and 20 months, respectively, after tonsillectomy, even when the symptoms of Crohn's disease worsened 69 months and 89 months after transplantation. A renal biopsy was performed 101 months after transplantation. Although IgA in the mesangium area was confirmed by immunohistochemical staining, no active lesion was seen. Tonsillectomy along with immunosuppressants for the graft might be an effective treatment for some patients with active recurrent IgA nephropathy.
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32
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Couser WG, Johnson RJ. The etiology of glomerulonephritis: roles of infection and autoimmunity. Kidney Int 2014; 86:905-14. [DOI: 10.1038/ki.2014.49] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Revised: 12/13/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023]
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Ambruzs JM, Walker PD, Larsen CP. The histopathologic spectrum of kidney biopsies in patients with inflammatory bowel disease. Clin J Am Soc Nephrol 2014; 9:265-70. [PMID: 24262508 PMCID: PMC3913236 DOI: 10.2215/cjn.04660513] [Citation(s) in RCA: 138] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND OBJECTIVES Kidney disease as a complication of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), has been the subject of case reports. However, no cases series examining IBD and kidney disease has been published to date. This study aimed to evaluate a large series of kidney biopsy specimens from patients with IBD to better define the spectrum and relative frequencies of IBD-associated kidney pathology. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective review of native kidney biopsy specimens obtained from March 2001 to June 2012 identified 83 patients with IBD. Standard processing of all biopsy specimens included light microscopy, immunofluorescence, and electron microscopy. RESULTS There were 45 cases of CD and 38 cases of UC represented. The most common indication for kidney biopsy was acute or chronic kidney failure (63% [52 of 83]) and nephrotic-range proteinuria (16% [13 of 83]). IgA nephropathy was the most common diagnosis (24% [20 of 83]), followed by interstitial nephritis (19% [16 of 83]), arterionephrosclerosis (12% [10 of 83]), acute tubular injury (8% [7 of 83]), proliferative GN (7% [6 of 83]), and minimal-change disease (5% [4 of 83]). When compared, the frequency of IgA nephropathy in IBD was significantly higher than in all other native renal biopsy specimens from the same time period (24% [20 of 83] versus 8% [2734 of 33,630]; P<0.001). Of the 16 cases of interstitial nephritis, 9 (56%) had current or recent past exposure to aminosalicylates, including all cases of granulomatous interstitial nephritis. CONCLUSIONS IBD is associated with a spectrum of kidney diseases most commonly affecting the glomerular and tubulointerstitial compartments. IgA nephropathy is the most frequent kidney biopsy diagnosis in IBD and has a significantly higher diagnostic prevalence compared with all non-IBD kidney biopsy specimens. This may reflect a common pathogenic mechanism. Although many cases of tubulointerstitial nephritis are related to aminosalicylate exposure, the possibility of a direct relationship with IBD cannot be ruled out.
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Affiliation(s)
| | - Patrick D. Walker
- Nephropath, Little Rock, Arkansas; and
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Christopher P. Larsen
- Nephropath, Little Rock, Arkansas; and
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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34
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Role of tumor necrosis factor inhibitor in granulomatous interstitial nephritis secondary to Crohn’s disease. Int Urol Nephrol 2012; 46:229-33. [DOI: 10.1007/s11255-012-0362-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2012] [Accepted: 12/12/2012] [Indexed: 01/14/2023]
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35
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Choi JY, Yu CH, Jung HY, Jung MK, Kim YJ, Cho JH, Kim CD, Kim YL, Park SH. A case of rapidly progressive IgA nephropathy in a patient with exacerbation of Crohn's disease. BMC Nephrol 2012; 13:84. [PMID: 22866754 PMCID: PMC3724487 DOI: 10.1186/1471-2369-13-84] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 07/28/2012] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND IgA nephropathy has been reported as a renal involvement in Crohn's disease. Crescentic IgA nephropathy, which accounts for fewer than 5% of cases of IgA nephropathy, has a poorer prognosis than other forms of crescentic glomerulonephritis. We recently experienced a case of rapidly progressive IgA nephropathy concurrent with exacerbation of Crohn's disease. CASE PRESENTATION An 18-year-old male diagnosed with Crohn's disease underwent a hemicolectomy 2 years prior previously. He had maintained a state of Crohn's disease remission with 5-aminosalicylic acid treatment. Four months prior to referral to the nephrology clinic, he experienced non-bloody diarrhea. He simultaneously developed proteinuria and microscopic hematuria with deterioration of renal function. Based on renal biopsy findings, the patient was diagnosed with crescentic IgA nephropathy. Immunostaining for interleukin-17 in renal tissue and previous exacerbated colonic ulcers was positive. Steroid pulse therapy was administered, followed by high-dose glucocorticoid and oral cyclophosphamide therapy. The patient's renal function recovered and his gastrointestinal symptoms were alleviated. CONCLUSIONS We report a case of crescentic IgA nephropathy presenting with exacerbation of Crohn's disease, and present a review of the literature focusing on the pathophysiologic relationship between these two conditions.
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Affiliation(s)
- Ji-Young Choi
- Division of Nephrology, Department of Internal Medicine, Kyungpook National University School of Medicine and Clinical Research Center for End Stage Renal Disease in Korea, 130 Dongduk-ro, Jung-gu, Daegu, South Korea
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Pipili C, Michopoulos S, Sotiropoulou M, Mpakirtzi T, Grapsa E. Is there any association between IgA nephropathy, Crohn's disease and Helicobacter pylori infection? Ren Fail 2012; 34:506-9. [PMID: 22260406 DOI: 10.3109/0886022x.2011.653774] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
A case of IgA nephropathy (IgAN) associated with Crohn's disease (CD) and preceded Helicobacter pylori (Hp) infection is described. Therapy with corticosteroids and azathioprine resulted in clinical improvement. The connection between IgAN and CD is well established, while tonsillar Hp is a potential antigen causative of IgAN. The three entities may reflect a common immunopathogenetic mechanism involving an IgA response to mucosal challenge.
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Affiliation(s)
- Chrysoula Pipili
- Department of Nephrology, Aretaieion University Hospital, Athens, Greece.
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37
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Filiopoulos V, Vlassopoulos D. Steroids with local enteric action in IgA nephropathy and the association between kidney and bowel disease. Nephrol Dial Transplant 2012; 27:1265-6. [DOI: 10.1093/ndt/gfr743] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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