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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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2
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van Hoeve K, Hoffman I. Renal manifestations in inflammatory bowel disease: a systematic review. J Gastroenterol 2022; 57:619-629. [PMID: 35834005 DOI: 10.1007/s00535-022-01903-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 06/27/2022] [Indexed: 02/04/2023]
Abstract
As extra-intestinal manifestations (EIMs) are frequent in inflammatory bowel disease (IBD) and affect morbidity and sometimes even mortality, vigilance in the surveillance of EIMs and installing the appropriate treatment are essential. Data on renal manifestations in patients with IBD are however rare. Nevertheless, up to 5-15% of adult patients with IBD will develop chronic kidney disease over time. The pathophysiology of renal involvement in patients with IBD is complex and poorly understood, with a wide range of renal disorders affecting the glomeruli and/or the tubular structure. Furthermore, medication used to treat IBD can be potentially nephrotoxic and metabolic complication due to the disease itself can furthermore cause renal damage. The aim of this systematic review is to provide an overview of the existing data in literature on these renal manifestations and complications in patients with IBD.
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Affiliation(s)
- Karen van Hoeve
- Department of Paediatric Gastroenterology and Hepatology and Nutrition, University Hospitals Leuven, Herestraat 49. 3000 KU, Louvain, Belgium.
| | - Ilse Hoffman
- Department of Paediatric Gastroenterology and Hepatology and Nutrition, University Hospitals Leuven, Herestraat 49. 3000 KU, Louvain, Belgium
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3
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Angeletti A, Arrigo S, Madeo A, Molteni M, Vietti E, Arcuri L, Coccia MC, Gandullia P, Ghiggeri GM. Different renal manifestations associated with very early onset pediatric inflammatory bowel disease: case report and review of literature. BMC Nephrol 2021; 22:146. [PMID: 33888087 PMCID: PMC8061217 DOI: 10.1186/s12882-021-02358-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 04/14/2021] [Indexed: 01/10/2023] Open
Abstract
Background Inflammatory bowel diseases are characterized by chronic inflammation of the gastrointestinal tract. In particular, Crohn disease and ulcerative colitis represent the two most common types of clinical manifestations. Extraintestinal manifestations of inflammatory bowel diseases represent a common complications, probably reflecting the systemic inflammation. Renal involvement is reported in 4–23% of cases. However, available data are limited to few case series and retrospective analysis, therefore the real impact of renal involvement is not well defined. Case presentation We report the case of a 10-years old male affected by very early onset unclassified-Inflammatory bowel diseases since he was 1-year old, presenting with a flare of inflammatory bowel diseases associated with acute kidney injury due to granulomatous interstitial nephritis. Of interest, at 7-year-old, he was treated for IgA nephropathy. To our knowledge, no previous reports have described a relapse of renal manifestation in inflammatory bowel diseases, characterized by two different clinical and histological phenotypes. Conclusions The link between the onset of kidney injuries with flares of intestinal inflammation suggest that nephritis maybe considered an extra-intestinal manifestation correlated with active inflammatory bowel disease. However, if granulomatous interstitial nephritis represents a cell-mediated hypersensitivity reaction than a true extraintestinal manifestation of inflammatory bowel diseases is still not clarified. We suggest as these renal manifestations here described may be interpreted as extraintestinal disorder and also considered as systemic signal of under treatment of the intestinal disease.
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Affiliation(s)
- A Angeletti
- Division of Nephrology, Dialysis, and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
| | - S Arrigo
- Pediatric Gastroenterology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - A Madeo
- Pediatric Gastroenterology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - M Molteni
- Division of Nephrology, Dialysis, and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - E Vietti
- Division of Nephrology, Dialysis, and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - L Arcuri
- Division of Nephrology, Dialysis, and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - M C Coccia
- Department of Pathology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - P Gandullia
- Pediatric Gastroenterology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - G M Ghiggeri
- Division of Nephrology, Dialysis, and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy.,Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
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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: 9] [Impact Index Per Article: 2.3] [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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Nurmi R, Pohjonen J, Metso M, Pörsti I, Niemelä O, Huhtala H, Mustonen J, Kaukinen K, Mäkelä S. Prevalence of Inflammatory Bowel Disease and Celiac Disease in Patients with IgA Nephropathy over Time. Nephron Clin Pract 2020; 145:78-84. [PMID: 33271538 DOI: 10.1159/000511555] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 09/09/2020] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION IgA nephropathy (IgAN) has been connected with increased intestinal permeability and subclinical intestinal mucosal inflammation as well as with inflammatory bowel disease (IBD) and celiac disease - nevertheless, the results are controversial. The prevalence of bowel diseases has increased over time in Western populations. Whether similar trend is seen among IgAN patients remains obscure. Our aim was to study the prevalence of IBD and celiac disease in IgAN patients over time. METHODS The study cohort consisted of altogether 629 patients with newly diagnosed IgAN during years 1976-2012. Data on diagnosis of IBD and celiac disease were retrospectively collected from medical records. Further, to detect unrecognized celiac disease, IgA-class tissue transglutaminase antibodies (tTGA) were measured from serum samples taken at the time of kidney biopsy during years 1980-2012 (defined as screen-detected celiac disease autoimmunity). RESULTS The prevalence of IBD among IgAN patients increased over time from 0 to 4.4%, while the prevalence of clinically diagnosed celiac disease decreased from 2.6 to 0.6%. Moreover, the number of screen-detected tTGA-positive cases decreased from the 1980s to the 21st century (2.8-0.7%). CONCLUSION The prevalence of IBD increased over time in IgAN patients, which exceeds the prevalence of 0.6% in Finnish general population. In parallel, the prevalence of celiac disease and screen-detected celiac disease autoimmunity decreased over time. The coexistence of IBD and IgAN is not negligible. Whether this finding is caused by the increase in the prevalence of IBD in the population or shared pathophysiology between IgAN and IBD remains a matter of further studies.
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Affiliation(s)
- Rakel Nurmi
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland,
| | - Jussi Pohjonen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Martti Metso
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Ilkka Pörsti
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.,Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Onni Niemelä
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Medical Research Unit, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Jukka Mustonen
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.,Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, 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 Health Technology, Tampere University, Tampere, Finland
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Robson KJ, Ooi JD, Holdsworth SR, Rossjohn J, Kitching AR. HLA and kidney disease: from associations to mechanisms. Nat Rev Nephrol 2018; 14:636-655. [DOI: 10.1038/s41581-018-0057-8] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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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: 19] [Impact Index Per Article: 2.1] [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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Dai CS, Chu CC, Chen SF, Sun CY, Lin M, Lee CC. Association between human leucocyte antigen subtypes and risk of end stage renal disease in Taiwanese: a retrospective study. BMC Nephrol 2015; 16:177. [PMID: 26518904 PMCID: PMC4627610 DOI: 10.1186/s12882-015-0165-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 10/14/2015] [Indexed: 02/06/2023] Open
Abstract
Background End stage renal disease (ESRD) is prevalent in Taiwan. Human leukocyte antigens (HLA) have been found to be associated with the pathogenesis of autoimmune diseases, allergies and inflammatory bowel diseases, and there are emerging evidences of correlations between HLA genotypes and renal diseases such as diabetic nephropathy, IgA nephropathy, and glomerulonephritis. The aim of this study is to investigate detailed HLA subtypes in a case-control study of Taiwanese individuals. Methods The polymorphisms of HLA class I and II antigens in ESRD patients and a healthy control group were retrospectively analyzed. The information of 141 ESRD patients was obtained from the medical record of the Keelung branch of Chang Gung Memorial Hospital and was compared to the HLA type of a control group comprized of 190 healthy unrelated Taiwanese from one of our previous studies. In order to standardize the HLA designation of prior low-resolution typings with the more advanced DNA based typings, all HLA-A, −B and -DR were analyzed using a low resolution serologic equivalent. Results The current work suggests that HLA-DR3 (odds ratio = 1.91, 95 % CI = 1.098–3.324, P = 0.024, Pc = 0.312) and HLA-DR11 (odds ratio = 2.06, 95 % CI = 1.133–3.761, P = 0.021, Pc = 0.273) may represent susceptibility risk factors for the development of ESRD in Taiwanese individuals. On the other hand, HLA-DR8 (odds ratio = 0.47, 95 % CI = 0.236–0.920, p = 0.027. Pc = 0.351) may be a protective factor. HLA-A and -B antigens did not show any contribution of progression to ESRD. However, we note that the significance of all these findings is lost when the results are corrected for multiple comparisons according to Bonferroni. Further investigation with a larger group of patients and control is needed to resolve this issue. Conclusions HLA typing might be a useful clinical method for screening patients with high risk of progression to ESRD.
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Affiliation(s)
- Ciou-Sia Dai
- Department of Internal Medicine, Division of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan.
| | - Chen-Chung Chu
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. .,Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan.
| | - Shin-Fan Chen
- Department of Internal Medicine, Division of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan.
| | - Chiao-Yin Sun
- Department of Internal Medicine, Division of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan.
| | - Marie Lin
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
| | - Chin-Chan Lee
- Department of Internal Medicine, Division of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan. .,Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan.
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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: 21] [Impact Index Per Article: 1.6] [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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Oikonomou K, Kapsoritakis A, Eleftheriadis T, Stefanidis I, Potamianos S. Renal manifestations and complications of inflammatory bowel disease. Inflamm Bowel Dis 2011; 17:1034-45. [PMID: 20842645 DOI: 10.1002/ibd.21468] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Accepted: 07/29/2010] [Indexed: 12/11/2022]
Abstract
Renal manifestations and complications are not rare in patients with inflammatory bowel disease (IBD) and may present as nephrolithiasis, amyloidosis, tubulointerstitial nephritis, and glomerulonephritis. Symptoms of renal impairment are not always specific and since the underlying bowel disease is preponderant, renal function deterioration may be underestimated. Additionally, medical treatment of patients with IBD such as aminosalicylates, cyclosporine, and tumor necrosis factor-α inhibitors can cause renal complications, although direct correlation to bowel disease is not always clear. The well-documented renal manifestations and complications of IBD, as well as the possible renal side effects of new drugs, emphasize the need for periodic evaluation of renal function. New markers of renal function may facilitate early diagnosis and unravel the complex mechanisms responsible for kidney damage. The purpose of this review is to summarize the renal manifestations and complications as well as the markers of renal function utilized in IBD, attempting to shed more light on the pathophysiology of renal damage in IBD.
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Affiliation(s)
- Konstantinos Oikonomou
- Department of Gastroenterology, University of Thessaly, School of Medicine, Larissa, Greece.
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Krasowska-Kwiecień A, Sancewicz-Pach K, Moczulska A. Idiopathic nephrotic syndrome in Polish children - its variants and associations with HLA. Pediatr Nephrol 2006; 21:1837-46. [PMID: 16967287 DOI: 10.1007/s00467-006-0271-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2006] [Revised: 07/07/2006] [Accepted: 07/11/2006] [Indexed: 10/24/2022]
Abstract
HLA-DR and HLA-DQ antigens were investigated in 127 Polish children with idiopathic nephrotic syndrome (INS) followed-up for the median time of 11 years (minimum 7 years). HLA typing was performed using the polymerase chain reaction sequence-specific oligonucleotide probing technique and the microlymphocytotoxicity test. Histopathologic INS categories and a response to therapy were analyzed according to particular HLA associations. The results were compared with 330 healthy individuals. In INS children, we observed an increased frequency of HLA-DR7, DR3/7, DQ2 and DQ8, whereas HLA-DR13, DR15, DQ5 and DQ6 were decreased. In minimal change nephrotic syndrome, a relationship with HLA-DR3, DR7, DR3/7 and DQ2 was found. Evolved from minimal changes, focal segmental glomerulosclerosis was associated with HLA-DR7, while primary focal segmental glomerulosclerosis with HLA-DR4 and DQ8. In steroid-dependence and secondary steroid-resistance, an increased frequency of HLA-DR3, DR7, DR3/7 and DQ2 was documented. In contrast, primary steroid-resistant nephrotic syndrome was associated with HLA-DR4 and DQ8. Steroid-dependent patients bearing HLA-DR3 achieved longer remissions after chlorambucil therapy compared with HLA-DR3-negative. In steroid-resistant focal segmental glomerulosclerosis, a reduced response to cyclosporine A was associated with HLA-DR4. Associations with HLA differentiate between pathoanatomic entities of INS and may influence a response to immunosuppressive therapy.
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Affiliation(s)
- Aleksandra Krasowska-Kwiecień
- Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University, 265 Wielicka St., 30-663 Cracow, Poland.
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Forshaw MJ, Guirguis O, Hennigan TW. IgA nephropathy in association with Crohn's disease. Int J Colorectal Dis 2005; 20:463-5. [PMID: 15668785 DOI: 10.1007/s00384-004-0696-z] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/05/2004] [Indexed: 02/04/2023]
Abstract
BACKGROUND Urological complications of inflammatory bowel disease are seen in up to 25% of patients, but renal parenchymal disease is rarely reported. CASE REPORT The authors describe a case of a 29-year-old man with clinical and radiological features of ileocaecal Crohn's disease. He had previously been investigated for painless macroscopic haematuria and a renal biopsy had revealed IgA nephropathy. Despite medical treatment, regular exacerbations of Crohn's disease were associated with deterioration in renal function and the development of haematuria. The patient eventually underwent surgical resection of the terminal ileum and caecum. His renal disease has remained quiescent for the last 5 years following resection.
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Affiliation(s)
- M J Forshaw
- Department of Surgery, Princess Royal University Hospital, Farnborough Common, Orpington, Kent BR6 8ND, UK.
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Nicholas A. K, Jacques P. B. Immune‐Mediated Diseases Involving Basement Membranes. CURRENT TOPICS IN MEMBRANES 2005. [DOI: 10.1016/s1063-5823(05)56011-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Park MH, Song EY, Ahn C, Oh KH, Yang J, Kang SJ, Lee HS. Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans. ACTA ACUST UNITED AC 2004; 62:505-11. [PMID: 14617034 DOI: 10.1046/j.1399-0039.2003.00141.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) is occurring at high prevalence in most Asian endemic areas. There have been some reports on human leucocyte antigen (HLA) associations with HBV infections; however, HLA association with HBV-GN has been rarely reported. Forty-six adult Korean patients with HBV-GN (42 male and four female patients, age 20-66), 100 HBsAg (-) healthy controls, and 89 individuals with chronic HBV infection were studied for HLA-DRB1 and DQB1 gene polymorphisms using high-resolution DNA typing methods. In HBV-GN patients, a strong association with HLA-DR2 was observed compared with HBsAg (-) controls (OR = 4.0). Different HLA-DR2 alleles were associated with different pathologic subtypes of HBV-GN: DRB1*1502 with membranoproliferative glomerulonephritis (MPGN, n = 35) (OR = 14.5) and DRB1*1501 with membranous nephropathy (MN, n = 11) (OR = 3.8). HLA-DQB1*0601, strongly linked to DRB1*1502, was also associated with MPGN subtype of HBV-GN (OR = 4.3). All these associations were also significant compared with chronic HBV infection group. For chronic HBV infection per se, DRB1*1302, DQB1*0402, and DQB1*0604 had some protective effect (OR = 0.4, OR = 0.3, and OR = 0.1, respectively), and DRB1*1101 was weakly associated (OR = 4.6) in Koreans. These results suggest that HLA-DR or related genetic factor is associated with disease susceptibility to HBV-GN in Koreans, and different pathologic subtypes of HBV-GN are influenced by the genetic factors of the patients.
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Affiliation(s)
- M H Park
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
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De Siati L, Paroli M, Ferri C, Muda AO, Bruno G, Barnaba V. Immunoglobulin A nephropathy complicating pulmonary tuberculosis. Ann Diagn Pathol 1999; 3:300-3. [PMID: 10556477 DOI: 10.1016/s1092-9134(99)80026-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
A 31-year-old man who presented with smear- and culture-negative pulmonary tuberculosis had associated macroscopic hematuria, elevation of serum creatinine and immunoglobulin A (IgA) levels, overt proteinuria, and peripheral edema. Renal biopsy revealed focal mesangial proliferation with IgA deposits, and a diagnosis of IgA nephropathy was made. The patient received treatment with isoniazide and rifampin. After 4 months, pulmonary lesions were almost completely healed, and a significant improvement of creatinine clearance with normalization of serum creatinine and IgA levels and disappearance of proteinuria were observed. Treatment with isoniazide and rifampin was discontinued after 6 months, without reappearance of either pulmonary or renal symptoms. Two years after the diagnosis of IgA nephropathy, the patient is in good general condition. Serum creatinine and IgA levels are normal, proteinuria is absent, and there is neither macrohematuria nor microhematuria. These findings suggest that IgA nephropathy may be a consequence of tuberculosis, possibly due to an abnormal IgA-mediated immune response against Mycobacterium tuberculosis with formation of nephrotoxic immune complexes.
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MESH Headings
- Adult
- Anti-Bacterial Agents
- Antibiotics, Antitubercular/therapeutic use
- Creatinine/blood
- Creatinine/urine
- Drug Therapy, Combination/therapeutic use
- Fluorescent Antibody Technique, Direct
- Glomerulonephritis, IGA/diagnosis
- Glomerulonephritis, IGA/drug therapy
- Glomerulonephritis, IGA/etiology
- Hematuria/diagnosis
- Hematuria/drug therapy
- Hematuria/etiology
- Humans
- Immunoglobulin A/analysis
- Isoniazid/therapeutic use
- Male
- Proteinuria/diagnosis
- Proteinuria/drug therapy
- Proteinuria/etiology
- Rifampin/therapeutic use
- Tomography, X-Ray Computed
- Treatment Outcome
- Tuberculosis, Pulmonary/complications
- Tuberculosis, Pulmonary/diagnosis
- Tuberculosis, Pulmonary/drug therapy
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Affiliation(s)
- L De Siati
- Department of Experimental Medicine, Andrea Cesalpino Foundation, Rome, Italy
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Winn MP, Alkhunaizi AM, Bennett WM, Garber RL, Howell DN, Butterly DW, Conlon PJ. Focal segmental glomerulosclerosis: a need for caution in live-related renal transplantation. Am J Kidney Dis 1999; 33:970-4. [PMID: 10213658 DOI: 10.1016/s0272-6386(99)70435-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Focal segmental glomerulosclerosis (FSGS) has increasingly been recognized to occur in a familial pattern. We have observed the development of biopsy-confirmed FSGS and subsequent end-stage renal disease (ESRD) in one live related kidney donor and ESRD without biopsy in another. Both donors had family members with ESRD secondary to FSGS. Both donors were apparently healthy by routine physical examination, urinalysis, and serum creatinine at the time of evaluation as live related donors. We believe these cases emphasize the need for great caution when evaluating siblings as potential live related donors.
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Affiliation(s)
- M P Winn
- Department of Medicine, Department of Medicine, Department of Pathology, Duke University Medical Center, Oregon Health Sciences University, West Wendover Ave, Durham, NC, USA
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21
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Gerbase-DeLima M, Pereira-Santos A, Sesso R, Temin J, Aragão ES, Ajzen H. Idiopathic focal segmental glomerulosclerosis and HLA antigens. Braz J Med Biol Res 1998; 31:387-9. [PMID: 9698788 DOI: 10.1590/s0100-879x1998000300010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS). HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin) with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P < 0.05). In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease.
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Affiliation(s)
- M Gerbase-DeLima
- Departamento de Pediatria, Escola Paulista de medicina, Universidade Federal de São Paulo, Brasil.
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Masaki T, Yorioka N, Taniguchi Y, Ogawa T, Naito T, Nishiki T, Harada Y, Yamakido M. Role of tenascin in human immunoglobulin A nephropathy. J Int Med Res 1997; 25:247-254. [PMID: 9364287 DOI: 10.1177/030006059702500502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Tenascin is a component of the extracellular matrix that responds rapidly to inflammation or injury. The activity index and chronicity index of immunoglobulin A nephropathy are mainly used to decide whether or not steroid therapy is indicated, but are sometimes difficult to evaluate histologically. We investigated whether tenascin staining of the glomeruli was an indicator of the activity or chronicity indices in patients with immunoglobulin A nephropathy. Tenascin staining was evaluated immunohistochemically in 38 renal specimens, including 32 from patients with immunoglobulin A nephropathy and six from control kidneys, and the extent of staining was scored. Tenascin staining was correlated with the chronicity index (r = 0.643, P < 0.0003) but not with the activity index.
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Affiliation(s)
- T Masaki
- Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan
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23
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Wyatt RJ, Emancipator SN, Kon V, Waldo FB, Donadio J, Grande JP, Andreoli SP, Glassock RJ. IgA nephropathy databank: development of a system for management of renal biopsy acquired data. Am J Kidney Dis 1997; 29:817-28. [PMID: 9186067 DOI: 10.1016/s0272-6386(97)90455-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- R J Wyatt
- Department of Pediatrics, University of Tennesee, Memphis, USA
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Fennessy M, Hitman GA, Moore RH, Metcalfe K, Medcraft J, Sinico RA, Mustonen JT, D'Amico G. HLA-DQ gene polymorphism in primary IgA nephropathy in three European populations. Kidney Int 1996; 49:477-80. [PMID: 8821832 DOI: 10.1038/ki.1996.67] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
MHC Class II genes may contribute to susceptibility to IgA nephropathy (IgAN). We have previously identified a restriction fragment length polymorphism (RFLP) of the DQB1 region that associated with IgAN in British Caucasoids. However, another group, while demonstrating a DQB1 association, was unable to confirm our finding. MHC molecules are heterodimers consisting of an alpha and beta chain, and thus polymorphism of the DQA1 alpha chain may also be important to disease pathogenesis in IgAN. Therefore, we have determined DQA1 alleles and re-examined DQB1 alleles in British Caucasoids with IgAN using an approach that can differentiate between the common DQ alleles; we have also extended our studies to Caucasoid populations from Northern and Southern Europe, thereby addressing the possibility of variation in genetic susceptibility between populations. DNA was prepared from IgAN patients (British, N = 105; Italian, N = 71; Finnish, N = 48) and healthy controls (British, N = 111; Italian, N = 63; Finnish, N = 41). DQA1 alleles were identified by TaqI RFLP and Southern blotting; alleles that could not be fully resolved by Taq Southern blotting were identified by PCR-RFLP. DQB1 alleles were identified by polymerase chain reaction (PCR) based technique (PCR-RFLP). No consistent association of DQ alleles were found between the populations studied. In British patients a decreased frequency of DQB1*0201 was observed (P = 0.008), in Finnish patients a decreased frequency of DQB1*0602 was observed (P = 0.01), and in Italian patients no association between DQ markers and IgAn was found. These data demonstrate population variation in disease association, but no strong or consistent association in the DQ region.
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Affiliation(s)
- M Fennessy
- Medical Unit, Royal London Hospital, England, United Kingdom
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25
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Abstract
IgAN is the most common type of glomerulonephritis worldwide, and is found more in men and distinctly less in blacks. It presents with macroscopic hematuria in about 40 to 45% of patients, with microscopic hematuria and proteinuria in about 35 to 40%, and with nephrotic syndrome or acute renal failure in the remainder. The diagnosis continues to rely on the finding of the dominant or codominant mesangial deposition of IgA on immunohistologic examination of the kidney. No blood or urine test is sufficiently reliable for diagnosis. While the pathogenesis remains unknown, accumulating evidence suggests that polyclonal stimulation of immunoglobulins perhaps coupled with structural abnormalities of IgA play pivotal roles. These defects may account for the variety of autoantibodies detected in patients with both IgAN and HSP. While IgAN has an indolent course, about 30% of patients will reach ESRD after 20 years, particularly in those who present with hypertension, heavy proteinuria or renal insufficiency. At present, therapy is disappointing, but immunoglobulin supplementation and newer agents that interrupt the pathways of mesangial proliferation and sclerosis hold promise for the future. Kidney transplantation has shown excellent allograft survival.
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Affiliation(s)
- J H Galla
- University of Cincinnati Medical Center, Ohio 45267-0585, USA
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