Renal AA Amyloidosis Associated with Inflammatory Bowel Disease

Renal AA Amyloidosis Associated with Inflammatory Bowel Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Renal AA Amyloidosis Associated with Inflammatory Bowel Disease Najla Zran, Soumaya Chargui, Awatef Azzabi, Sahar Agrebi, Yosra Guedri, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8925868/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Introduction: Renal amyloidosis related to serum amyloid A (AA amyloidosis) is a rare but severe complication of inflammatory bowel disease (IBD), associated with significant renal morbidity; this study aimed to describe its clinical features, management, and renal outcomes in a multicenter cohort. Methods: We conducted a retrospective study across two tertiary referral nephrology centers including patients with IBD and renal AA amyloidosis. Data were collected from 1990 to 2022 in the nephrology department of Charles Nicolle hospital Tunis and from 2008 to 2022 in the nephrology department of Sahloul hospital Sousse. Results: Seventeen patients with IBD : 14 with Crohn’s disease and 3 with ulcerative colitis were included. The median age at diagnosis was 37 years [range: 19–68], with a male predominance. The median interval between IBD diagnosis and detection of renal involvement was 3 years. All patients had heavy proteinuria (>3 g/24 h), with nephrotic syndrome in 15 patients. Reduced kidney function was observed in eight patients. Diagnosis was established by minor salivary gland biopsy in 10 patients and by renal biopsy in seven. Nine patients continued previous IBD therapy, five received colchicine, two systemic corticosteroids, and one anti–TNF-α therapy. Renal outcomes were poor. One patient was dialysis-dependent at baseline, and eight patients progressed to end-stage kidney disease requiring dialysis over a median time of 19 months. Conclusion: Renal AA amyloidosis represents a serious complication of IBD with poor renal prognosis. Early diagnosis and optimal control of intestinal inflammation are essential to prevent irreversible kidney damage. Crohn’s disease Ulcerative colitis Amyloidosis Renal involvement Figures Figure 1 1. Introduction Renal AA amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), resulting from chronic systemic inflammation and sustained elevation of serum amyloid A (SAA). Crohn’s disease (CD) is more frequently implicated than ulcerative colitis (UC), although the overall prevalence remains low. Renal involvement is the most common manifestation, typically presenting with proteinuria, nephrotic syndrome and may lead to kidney failure (1). Despite its clinical significance, data on the characteristics, management, and long-term outcomes of IBD-associated AA amyloidosis remain limited. This study aimed to describe the clinical, biological, and histological features, and renal prognosis of IBD-associated AA amyloidosis in a multicenter cohort. 2. Methods We conducted a retrospective, multicenter study including patients with IBD diagnosed with renal AA amyloidosis. Data were collected from 1990 to 2022 at the Nephrology Department of Charles Nicolle Hospital, Tunis, and from 2008 to 2022 at the Nephrology Department of Sahloul Hospital, Sousse. The difference in inclusion periods reflects the earlier establishment and longer clinical activity of the first center. Data on patients’ demographics, clinical characteristics, laboratory and histological findings, treatments, and outcomes were collected from medical records. Continuous variables are presented as median [range], and categorical variables as counts. Given the small cohort size, only descriptive analyses were conducted. Clinical data included IBD type, disease duration, disease location, history of surgery, IBD activity at the time of amyloidosis diagnosis, extra-intestinal manifestations, and chronic suppurative complications. Renal involvement was assessed using proteinuria, serum creatinine, and estimated glomerular filtration rate (eGFR, MDRD formula). Physical examination findings were also recorded. Amyloidosis diagnosis was confirmed by minor salivary gland biopsy or renal biopsy. Amyloid deposits were systematically typed in all patients to confirm serum amyloid A (SAA) amyloidosis. 3. Results Patient characteristics: Renal amyloidosis was identified in 17 patients, including 13 from the Nephrology Department of Charles Nicolle Hospital and 4 from the Nephrology Department of Sahloul Hospital, including 14 with CD and 3 with UC. There was a male predominance, with a male-to-female ratio of 4.66, and the median age at diagnosis was 37 years [range: 19-68]. Disease location and history: The median interval between IBD diagnosis and detection of renal involvement was 3 years, with renal amyloidosis being the initial presentation of IBD in two patients. Eight patients were experiencing an active IBD flare at the time of amyloidosis diagnosis. Among CD patients, ten had ileocolonic involvement and four had isolated ileal disease. Two patients had a history of colectomy, performed 22 and 2 years prior to amyloidosis diagnosis. Complications and extra-intestinal manifestations: Chronic suppurative complications were present in six patients, including perineal fistulas in three and anal margin abscesses in three. Extra-intestinal manifestations were observed in eight patients: spondyloarthritis in four, arthralgias in three, and uveitis in one. Clinical examination: Edema was noted in 12 patients, including generalized anasarca in three. Median systolic and diastolic blood pressures were 110 mmHg [range: 90–150] and 60 mmHg [range: 40–90], respectively, with orthostatic hypotension in three cases. Palpable ulnar nerves and digital clubbing were observed in two patients each, while hepatomegaly and macroglossia were noted in one patient. Laboratory findings: Revealed hypoalbuminemia and reduced total serum protein, with variable renal function (median serum creatinine 98 µmol/L, median eGFR 57.4 mL/min/1.73 m²). Detailed biochemical and renal parameters are provided in Table 1 . Renal involvement and biopsy: All patients exhibited significant proteinuria (>3 g/24 h), with a median of 5.2 g/24 h [range: 3.12–20.7]. Nephrotic syndrome (NS) was observed in 15 patients: pure in seven. Impaired renal function occurred in eight patients, including one patient with end-stage kidney disease (ESKD) at presentation. Diagnosis of amyloidosis was confirmed by minor salivary gland biopsy in 10 patients and renal biopsy in seven patients. Histology revealed amorphous, acellular, weakly basophilic deposits, sometimes striated on standard stains, Congo red positivity, and characteristic green-yellow birefringence under polarized light. Amyloid deposits positive for SAA were identified on immunohistochemistry (Figure 1) . Treatment: Nine patients continued prior IBD therapy. Five received colchicine, two systemic corticosteroids, and one was treated with an anti-TNF-α agent (Table 2) . Renal outcomes: The median eGFR at one year of follow-up was 16.4 mL/min/1.73 m² . One patient was dialysis-dependent at baseline , and eight patients progressed to end-stage kidney disease requiring dialysis over a median time of 19 months [2-108]. 4. Discussion AA amyloidosis, formerly known as reactive or secondary amyloidosis, results from hepatic and macrophage synthesis of SAA in response to chronic inflammatory stimuli (2). The association between AA amyloidosis and IBD was first described by Moschkowitz in 1936 (3). A systematic review of 795 publications over the past four decades identified IBD among the most frequent causes of AA amyloidosis (2). Prevalence varies across studies; in a systematic review of cross-sectional studies and case series, AA amyloidosis occurred in 0.53% of IBD cases, with CD more frequently affected than UC (1.05% vs. 0.08%) (1). In previous series, renal amyloidosis was the most common renal manifestation in 27.5% of cases (A. Fayed et al.) (3), while another study reported AA amyloidosis in 10.9% of CD patients, with no UC cases affected (Dincer et al.) (4). Our cohort demonstrated a male predominance, consistent with previous reports [1,5,6,7]. The median IBD duration before amyloidosis diagnosis in our study was 3 years, with amyloidosis revealing IBD in two patients. Tosca et al. reported that AA amyloidosis typically complicates long-standing IBD, with a mean interval of 14 years (1). However, simultaneous diagnosis of amyloidosis and IBD is not rare; in a 25-year cohort of 500 IBD patients, five of 18 AA amyloidosis cases were diagnosed concurrently (5). Chronic suppurative complications and extra-intestinal manifestations were frequently observed among the patients. Literature data suggest that AA amyloidosis frequently occurs in patients with extensive or fistulizing disease, with up to two-thirds of patients affected by fistulas or abscesses (1). Moreover, extra-intestinal manifestations, particularly articular and cutaneous, may contribute to persistent inflammation, potentially explaining the high prevalence of AA amyloidosis in IBD (6). Clinically, renal involvement with proteinuria in all patients, nephrotic syndrome in 15, and renal insufficiency in eight patients, aligning with prior studies showing that 90% of IBD-related AA amyloidosis presents with renal manifestations, including nephrotic syndrome, proteinuria, and/or Impaired renal function (7). Diagnosis was confirmed by minor salivary gland biopsy and renal biopsy. Organ biopsy remains the gold standard, with less invasive methods preferred. Digestive endoscopic biopsies are particularly valuable in IBD: one study in 408 CD patients reported amyloid deposits in 83% of gastric, 100% of duodenal, and 67% of colonic/rectal biopsies (8). Treatment of AA amyloidosis primarily aims to control the underlying inflammatory state and reduce circulating SAA levels (9). To our knowledge, no prospective randomized studies have specifically evaluated therapies for AA amyloidosis in the context of IBD. In our cohort, nine patients continued prior IBD therapy, five received colchicine, two systemic corticosteroids, and one an anti–TNF-α agent. Although these therapies have been used in other series, their efficacy remains unproven. Case reports and small series suggest that anti–TNF-α therapy, particularly infliximab, may reduce SAA levels, decrease proteinuria, and stabilize renal function; however, the reversibility of established renal damage remains uncertain [1,10]. More recently, IL-6 receptor blockade with tocilizumab has shown promising results in reducing inflammation and SAA levels, though data in IBD-associated AA amyloidosis remain limited [1,10]. Renal prognosis was poor , with 9 of 17 patients progressing to ESKD over a median follow-up of 19 months . Similarly, Sharma et al. reported rapid progression to ESKD in patients with IBD-associated AA amyloidosis (10). In a larger cohort, Sattianayagam et al. observed progression to ESKD in 68% of patients over a median follow-up of 6.3 years , findings that are consistent with our results (9). 5. Conclusion Renal AA amyloidosis is a rare but severe complication of inflammatory bowel disease, predominantly affecting patients with CD and chronic or complicated disease courses. Early recognition, systematic monitoring of renal function, and aggressive control of underlying inflammation are crucial to prevent progression to ESKD. Despite available therapies, renal prognosis remains poor, underscoring the need for further prospective studies to establish effective management strategies in this high-risk population. Declarations 6. Author Contributions N.Z.: Study conception and design, patient recruitment, data collection, data analysis, interpretation of data and drafting of the manuscript. S.C.: Data collection and critical revision of the manuscript. A.A.: Patient recruitment and interpretation of clinical data. S.A.: Study conception and statistical analysis. Y.G.: Manuscript revision and interpretation of data. N.S.: Histopathological analysis. S.M.: Histopathological analysis. H.K.: Critical revision of the manuscript. M.H.: Histopathological analysis and interpretation of data. D.Z.: Study supervision and critical revision of the manuscript. E.A.: Study supervision and critical revision of the manuscript. All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work. 7. Funding Statement This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Data were generated as part of routine clinical practice. 8. Data Availability Statement The data supporting the findings of this study are available from the corresponding author upon reasonable request. Due to ethical and privacy considerations, the data are not publicly available. 9. A cknowledgements The authors confirm that the generative AI tool ChatGPT (GPT-5 mini) was used solely to improve the clarity and fluency of the English text. All scientific content, data interpretation, and conclusions are the sole work of the authors. 10. Conflict of Interest There is no conflict of interest. 11. Ethical approval The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Charles Nicolle Hospital (Tunis, Tunisia). Given the retrospective design of the study and the use of fully anonymized data, written informed consent was waived by the Ethics Committee. 12. Consent for publication Not applicable. References Tosca Cuquerella J, Bosca-Watts MM, Anton Ausejo R, Tejedor Alonso S, Mora de Miguel F, Minguez Perez M. Amyloidosis in inflammatory bowel disease: a systematic review of epidemiology, clinical features, and treatment . J Crohns Colitis. 2016;10(10):1245–1253. Brunger AF, Nienhuis HLA, Bijzet J, Hazenberg BPC. Causes of AA amyloidosis: a systematic review. 2020;27(1):1–12. Abdel-Aziz M, Fayed A. Patterns of renal involvement in a cohort of patients with inflammatory bowel disease in Egypt. Acta Gastroenterol Belg. 2018;81:381–385. Dincer MT, Dincer ZT, Bakkaloglu OK, Yalin SF, Trabulus S, Celik AF, et al. Renal manifestations in inflammatory bowel disease: a cohort study during the biologic era. Med Sci Monit. 2022;28:e936497. Wester AL, Vatn MH, Fausa O. Secondary amyloidosis in inflammatory bowel disease: a study of 18 patients admitted to Rikshospitalet University Hospital, Oslo, from 1962 to 1998. Inflamm Bowel Dis. 2001;7(4):295–300. Greenstein AJ, Sachar DB, Nannan Panday AK, Dikman SH, Meyers S, Heimann T, et al. Amyloidosis and inflammatory bowel disease: a 50-year experience with 25 patients. Medicine (Baltimore). 1992;71(5):261–270. Serra I, Oller B, Mañosa M, Naves JE, Zabana Y, Cabré E, et al. Systemic amyloidosis in inflammatory bowel disease: retrospective study on its prevalence, clinical presentation, and outcome. J Crohns Colitis. 2010;4(3):269–274. Miyaoka M, Matsui T, Hisabe T, Yano Y, Hirai F, Takaki Y, et al. Clinical and endoscopic features of amyloidosis secondary to Crohn’s disease: diagnostic value of duodenal observation and biopsy. Dig Endosc. 2011;23(2):157–165. Sattianayagam PT, Gillmore JD, Pinney JH, Gibbs SDJ, Wechalekar AD, Gilbertson JA, et al. Inflammatory bowel disease and systemic AA amyloidosis. Dig Dis Sci. 2013;58(6):1689–1697. Sharma P, Aguilar R, Siddiqui OA, Nader MA. Secondary systemic amyloidosis in inflammatory bowel disease: a nationwide analysis. Ann Gastroenterol. 2017;30(5):504–511. Tables Table 1. Clinical, biological and histological characteristics of AA amyloidosis in patients with inflammatory bowel disease AA amyloidosis in IBD (n=17) CD/UC=14/3 Age in years, (median, range) 37 [19 - 68] Sexe ratio (H/F) 4.66 Years from IBD to AA amyloidosis (median, range) 3 [0 - 25] Disease-related complications, n Perianal disease 6 Extra-intestinal manifestations 8 Laboratory parameters, (median, range) Serum creatinine (µmol/L) 98 [39–1207] eGFR (mL/min/1.73 m²) 57.4 [4.4–247.1] Total serum protein (g/L) 47 [28–68] Serum albumin (g/L) 19 [5.4–34] CRP (mg/L) 28 [16–84] Proteinuria (g/24h) 5.2 [3.12–20.7] Clinical entities, n Nephrotic syndrome 15 Impaired renal function 8 Biopsies performed, n Minor Salivary gland biopsy 10 Renal biopsy 7 IBD - Inflammatory bowel disease; CD - Crohn disease; UC - Ulcerative colitis; eGFR - estimated glomerular filtration rate; CRP - C-reactive protein. Table 2. Therapeutic management and outcomes of AA amyloidosis in patients with inflammatory bowel disease AA amyloidosis in IBD (n=17) CD/UC=14/3 IBD therapy, n Systemic steroids 6 5-aminosalicylic-acid 7 Azathioprine 3 Anti-TNF-α 1 IBD related surgery, n 2 AA amyloidosis therapy, n Systemic steroids 2 Colchicine use 5 Anti-TNF-α 1 ESKD, n 9 IBD - Inflammatory bowel disease; CD - Crohn disease; UC - Ulcerative colitis; TNF - tumor necrosis factor; ESKD - End stage kidney disease. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 Mar, 2026 Reviews received at journal 24 Mar, 2026 Reviews received at journal 14 Mar, 2026 Reviewers agreed at journal 14 Mar, 2026 Reviewers agreed at journal 13 Mar, 2026 Reviewers invited by journal 12 Mar, 2026 Editor assigned by journal 12 Mar, 2026 Editor invited by journal 02 Mar, 2026 Submission checks completed at journal 28 Feb, 2026 First submitted to journal 28 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8925868","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606206946,"identity":"e786ff79-d9f6-438f-a4ac-7163aa9cc844","order_by":0,"name":"Najla 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ezzedine","middleName":"","lastName":"Abderrahim","suffix":""}],"badges":[],"createdAt":"2026-02-20 12:24:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8925868/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8925868/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104874271,"identity":"1b6ba254-227e-402d-bfed-e5222011fbb0","added_by":"auto","created_at":"2026-03-18 08:29:41","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":278125,"visible":true,"origin":"","legend":"\u003cp\u003eExtra-lobular amyloid deposits positive for serum amyloid A (SAA) were identified on immunohistochemistry\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8925868/v1/1a4798d157bd156738fc71c7.jpeg"},{"id":104874285,"identity":"c1c94031-9789-43ed-8bc0-2c963911398b","added_by":"auto","created_at":"2026-03-18 08:29:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1269621,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8925868/v1/ff981e3f-1348-42ac-821a-ad497807a802.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Renal AA Amyloidosis Associated with Inflammatory Bowel Disease","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eRenal AA amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), resulting from chronic systemic inflammation and sustained elevation of serum amyloid A (SAA). Crohn’s disease (CD) is more frequently implicated than ulcerative colitis (UC), although the overall prevalence remains low. Renal involvement is the most common manifestation, typically presenting with proteinuria,\u0026nbsp;nephrotic syndrome\u0026nbsp;and may lead to kidney failure\u0026nbsp;(1).\u003c/p\u003e\n\u003cp\u003eDespite its clinical significance, data on the characteristics, management, and long-term outcomes of IBD-associated AA amyloidosis remain limited. This study aimed to describe the clinical, biological, and histological features, and renal prognosis of IBD-associated AA amyloidosis in a multicenter cohort.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eWe conducted a retrospective, multicenter study including patients with IBD diagnosed with renal AA amyloidosis. Data were collected from 1990 to 2022 at the Nephrology Department of Charles Nicolle Hospital, Tunis, and from 2008 to 2022 at the Nephrology Department of Sahloul Hospital, Sousse. The difference in inclusion periods reflects the earlier establishment and longer clinical activity of the first center.\u003c/p\u003e\n\u003cp\u003eData on patients’ demographics, clinical characteristics, laboratory and histological findings, treatments, and outcomes were collected from medical records. Continuous variables are presented as median [range], and categorical variables as counts. Given the small cohort size, only descriptive analyses were conducted.\u003c/p\u003e\n\u003cp\u003eClinical data included IBD type, disease duration, disease location, history of surgery, IBD activity at the time of amyloidosis diagnosis, extra-intestinal manifestations, and chronic suppurative complications. Renal involvement was assessed using proteinuria, serum creatinine, and estimated glomerular filtration rate (eGFR, MDRD formula). Physical examination findings were also recorded.\u003c/p\u003e\n\u003cp\u003eAmyloidosis diagnosis was confirmed by minor salivary gland biopsy or renal biopsy. Amyloid deposits were systematically typed in all patients to confirm serum amyloid A (SAA) amyloidosis.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRenal amyloidosis was identified in 17 patients, including 13 from the Nephrology Department of Charles Nicolle Hospital and 4 from the Nephrology Department of Sahloul Hospital, including 14 with CD and 3 with UC. There was a male predominance, with a male-to-female ratio of 4.66, and the median age at diagnosis was 37 years [range: 19-68].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisease location and history:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median interval between IBD diagnosis and detection of renal involvement was 3 years, with renal amyloidosis being the\u0026nbsp;initial presentation of IBD\u0026nbsp;in two patients. Eight patients were experiencing an active IBD flare at the time of amyloidosis diagnosis.\u003cbr\u003e\u0026nbsp;Among CD patients, ten had ileocolonic involvement and four had isolated ileal disease. Two patients had a history of colectomy, performed 22 and 2 years prior to amyloidosis diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComplications and extra-intestinal manifestations:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Chronic suppurative complications were present in six patients, including perineal fistulas in three and anal margin abscesses in three. Extra-intestinal manifestations were observed in eight patients: spondyloarthritis in four, arthralgias in three, and uveitis in one.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical examination:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Edema was noted in 12 patients, including generalized anasarca in three. Median systolic and diastolic blood pressures were 110 mmHg [range: 90\u0026ndash;150] and 60 mmHg [range: 40\u0026ndash;90], respectively, with orthostatic hypotension in three cases. Palpable ulnar nerves and digital clubbing were observed in two patients each, while hepatomegaly and macroglossia were noted in one patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory findings:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRevealed hypoalbuminemia and reduced total serum protein, with variable renal function (median serum creatinine 98 \u0026micro;mol/L, median eGFR 57.4 mL/min/1.73 m\u0026sup2;). Detailed biochemical and renal parameters are provided in \u003cstrong\u003eTable 1\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRenal involvement and biopsy:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients exhibited\u0026nbsp;significant proteinuria\u0026nbsp;(\u0026gt;3 g/24 h), with a median of 5.2 g/24 h [range: 3.12\u0026ndash;20.7]. Nephrotic syndrome (NS) was observed in 15 patients: pure in seven.\u0026nbsp;Impaired renal function occurred in eight patients, including one patient with end-stage kidney disease (ESKD) at presentation.\u003c/p\u003e\n\u003cp\u003eDiagnosis of amyloidosis was confirmed by\u0026nbsp;minor salivary gland biopsy in 10 patients\u0026nbsp;and renal biopsy in seven patients. Histology revealed amorphous, acellular, weakly basophilic deposits, sometimes striated on standard stains, Congo red positivity, and characteristic green-yellow birefringence under polarized light.\u0026nbsp;Amyloid deposits positive for SAA were identified on immunohistochemistry\u003cstrong\u003e\u0026nbsp;(Figure 1)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment:\u003c/strong\u003e\u003cbr\u003eNine patients continued prior IBD therapy. Five received colchicine, two systemic corticosteroids, and one was treated with an anti-TNF-\u0026alpha; agent \u003cstrong\u003e(Table 2)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRenal outcomes:\u003c/strong\u003e\u003cbr\u003eThe median eGFR at one year of follow-up was\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003e16.4 mL/min/1.73 m\u0026sup2;\u003c/strong\u003e. \u003cstrong\u003eOne patient was dialysis-dependent at baseline\u003c/strong\u003e,\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003eeight patients progressed to end-stage kidney disease requiring dialysis\u003c/strong\u003eover a\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003emedian time of 19 months\u003c/strong\u003e\u0026nbsp;\u003c/strong\u003e[2-108].\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eAA amyloidosis, formerly known as reactive or secondary amyloidosis, results from hepatic and macrophage synthesis of SAA in response to chronic inflammatory stimuli\u0026nbsp;(2). The association between AA amyloidosis and IBD was first described by Moschkowitz in 1936 (3).\u0026nbsp;A systematic review of 795 publications over the past four decades identified IBD among the most frequent causes of AA amyloidosis (2). Prevalence varies across studies; in a systematic review of cross-sectional studies and case series, AA amyloidosis occurred in 0.53% of IBD cases, with CD more frequently affected than UC (1.05% vs. 0.08%) (1).\u0026nbsp;In previous series, renal amyloidosis was the most common renal manifestation in 27.5% of cases (A. Fayed et al.) (3), while another study reported AA amyloidosis in 10.9% of CD patients, with no UC cases affected (Dincer et al.)\u0026nbsp;(4). Our cohort demonstrated a male predominance, consistent with previous reports [1,5,6,7].\u003c/p\u003e\n\u003cp\u003eThe median IBD duration before amyloidosis diagnosis in our study was 3 years, with amyloidosis revealing IBD in two patients. Tosca et al. reported that AA amyloidosis typically complicates long-standing IBD, with a mean interval of 14 years (1). However, simultaneous diagnosis of amyloidosis and IBD is not rare; in a 25-year cohort of 500 IBD patients, five of 18 AA amyloidosis cases were diagnosed concurrently (5).\u003c/p\u003e\n\u003cp\u003eChronic suppurative complications and extra-intestinal manifestations were frequently observed among the patients.\u0026nbsp;Literature data suggest that AA amyloidosis frequently occurs in patients with extensive or fistulizing disease, with up to two-thirds of patients affected by fistulas or abscesses\u0026nbsp;(1). Moreover, extra-intestinal manifestations, particularly articular and cutaneous, may contribute to persistent inflammation, potentially explaining the high prevalence of AA amyloidosis in IBD\u0026nbsp;(6).\u003c/p\u003e\n\u003cp\u003eClinically, renal involvement with proteinuria in all patients, nephrotic syndrome in 15, and renal insufficiency in eight patients, aligning with prior studies showing that 90% of IBD-related AA amyloidosis presents with renal manifestations, including nephrotic syndrome, proteinuria, and/or\u0026nbsp;Impaired renal function (7).\u003c/p\u003e\n\u003cp\u003eDiagnosis was confirmed by\u0026nbsp;minor salivary gland biopsy\u0026nbsp;and renal biopsy. Organ biopsy remains the gold standard, with less invasive methods preferred. Digestive endoscopic biopsies are particularly valuable in IBD: one study in 408 CD patients reported amyloid deposits in 83% of gastric, 100% of duodenal, and 67% of colonic/rectal biopsies\u0026nbsp;(8).\u003c/p\u003e\n\u003cp\u003eTreatment of AA amyloidosis primarily aims to control the underlying inflammatory state and reduce circulating SAA levels (9). To our knowledge, no prospective randomized studies have specifically evaluated therapies for AA amyloidosis in the context of IBD. In our cohort, nine patients continued prior IBD therapy, five received colchicine, two systemic corticosteroids, and one an anti–TNF-α agent. Although these therapies have been used in other series, their efficacy remains unproven. Case reports and small series suggest that anti–TNF-α therapy, particularly infliximab, may reduce SAA levels, decrease proteinuria, and stabilize renal function; however, the reversibility of established renal damage remains uncertain [1,10]. More recently, IL-6 receptor blockade with tocilizumab has shown promising results in reducing inflammation and SAA levels, though data in IBD-associated AA amyloidosis remain limited [1,10].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRenal prognosis was poor\u003c/strong\u003e, with \u003cstrong\u003e9 of 17 patients progressing to ESKD\u003c/strong\u003e over a\u003cstrong\u003emedian follow-up of 19 months\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e Similarly, \u003cstrong\u003eSharma et al.\u003c/strong\u003ereported\u003cstrong\u003erapid progression to ESKD\u003c/strong\u003ein patients with IBD-associated AA amyloidosis (10). In a larger cohort, \u003cstrong\u003eSattianayagam et al.\u003c/strong\u003e observed progression to ESKD in \u003cstrong\u003e68% of patients\u003c/strong\u003e over a \u003cstrong\u003emedian follow-up of 6.3 years\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003efindings that are \u003cstrong\u003econsistent with our results\u003c/strong\u003e (9).\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eRenal AA amyloidosis is a rare but severe complication of inflammatory bowel disease, predominantly affecting patients with CD and chronic or complicated disease courses. Early recognition, systematic monitoring of renal function, and aggressive control of underlying inflammation are crucial to prevent progression to ESKD. Despite available therapies, renal prognosis remains poor, underscoring the need for further prospective studies to establish effective management strategies in this high-risk population.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e6.\u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN.Z.: Study conception and design, patient recruitment, data collection, data analysis, interpretation of data and drafting of the manuscript.\u003cbr\u003e\u0026nbsp;S.C.: Data collection and critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003eA.A.: Patient recruitment and interpretation of clinical data.\u003c/p\u003e\n\u003cp\u003eS.A.: Study conception and statistical analysis.\u003cbr\u003e\u0026nbsp;Y.G.: Manuscript revision and interpretation of data.\u003cbr\u003e\u0026nbsp;N.S.: Histopathological analysis.\u0026nbsp;\u003cbr\u003e\u0026nbsp;S.M.: Histopathological analysis.\u003cbr\u003e\u0026nbsp;H.K.: Critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003eM.H.: Histopathological analysis and interpretation of data.\u003cbr\u003e\u0026nbsp;D.Z.: Study supervision and critical revision of the manuscript.\u003cbr\u003e\u0026nbsp;E.A.: Study supervision and critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.\u0026nbsp; \u0026nbsp;Funding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Data were generated as part of routine clinical practice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e8.\u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available from the corresponding author upon reasonable request. Due to ethical and privacy considerations, the data are not publicly available.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e9.\u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003cstrong\u003ecknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors confirm that the generative AI tool ChatGPT (GPT-5 mini) was used solely to improve the clarity and fluency of the English text. All scientific content, data interpretation, and conclusions are the sole work of the authors.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e10.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eConflict of Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e11.\u0026nbsp;Ethical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Charles Nicolle Hospital (Tunis, Tunisia). Given the retrospective design of the study and the use of fully anonymized data, written informed consent was waived by the Ethics Committee.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e12.\u0026nbsp;Consent for publication\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTosca Cuquerella J, Bosca-Watts MM, Anton Ausejo R, Tejedor Alonso S, Mora de Miguel F, Minguez Perez M. Amyloidosis in inflammatory bowel disease: a systematic review of epidemiology, clinical features, and treatment\u003cstrong\u003e. \u003c/strong\u003e\u003cstrong\u003eJ Crohns Colitis.\u003c/strong\u003e 2016;10(10):1245\u0026ndash;1253.\u003c/li\u003e\n\u003cli\u003eBrunger AF, Nienhuis HLA, Bijzet J, Hazenberg BPC. Causes of AA amyloidosis: a systematic review. 2020;27(1):1\u0026ndash;12.\u003c/li\u003e\n\u003cli\u003eAbdel-Aziz M, Fayed A. Patterns of renal involvement in a cohort of patients with inflammatory bowel disease in Egypt. \u003cstrong\u003eActa Gastroenterol Belg.\u003c/strong\u003e 2018;81:381\u0026ndash;385.\u003c/li\u003e\n\u003cli\u003eDincer MT, Dincer ZT, Bakkaloglu OK, Yalin SF, Trabulus S, Celik AF, et al. Renal manifestations in inflammatory bowel disease: a cohort study during the biologic era. \u003cstrong\u003eMed Sci Monit.\u003c/strong\u003e 2022;28:e936497.\u003c/li\u003e\n\u003cli\u003eWester AL, Vatn MH, Fausa O. Secondary amyloidosis in inflammatory bowel disease: a study of 18 patients admitted to Rikshospitalet University Hospital, Oslo, from 1962 to 1998. \u003cstrong\u003eInflamm Bowel Dis.\u003c/strong\u003e 2001;7(4):295\u0026ndash;300.\u003c/li\u003e\n\u003cli\u003eGreenstein AJ, Sachar DB, Nannan Panday AK, Dikman SH, Meyers S, Heimann T, et al. Amyloidosis and inflammatory bowel disease: a 50-year experience with 25 patients. \u003cstrong\u003eMedicine (Baltimore).\u003c/strong\u003e 1992;71(5):261\u0026ndash;270.\u003c/li\u003e\n\u003cli\u003eSerra I, Oller B, Ma\u0026ntilde;osa M, Naves JE, Zabana Y, Cabr\u0026eacute; E, et al. Systemic amyloidosis in inflammatory bowel disease: retrospective study on its prevalence, clinical presentation, and outcome. \u003cstrong\u003eJ Crohns Colitis.\u003c/strong\u003e 2010;4(3):269\u0026ndash;274.\u003c/li\u003e\n\u003cli\u003eMiyaoka M, Matsui T, Hisabe T, Yano Y, Hirai F, Takaki Y, et al. Clinical and endoscopic features of amyloidosis secondary to Crohn\u0026rsquo;s disease: diagnostic value of duodenal observation and biopsy. \u003cstrong\u003eDig Endosc.\u003c/strong\u003e 2011;23(2):157\u0026ndash;165.\u003c/li\u003e\n\u003cli\u003eSattianayagam PT, Gillmore JD, Pinney JH, Gibbs SDJ, Wechalekar AD, Gilbertson JA, et al. Inflammatory bowel disease and systemic AA amyloidosis. \u003cstrong\u003eDig Dis Sci.\u003c/strong\u003e 2013;58(6):1689\u0026ndash;1697.\u003c/li\u003e\n\u003cli\u003eSharma P, Aguilar R, Siddiqui OA, Nader MA. Secondary systemic amyloidosis in inflammatory bowel disease: a nationwide analysis. \u003cstrong\u003eAnn Gastroenterol.\u003c/strong\u003e 2017;30(5):504\u0026ndash;511.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e\u003cstrong\u003eClinical, biological and histological characteristics of AA amyloidosis in patients with inflammatory bowel disease\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAA amyloidosis in IBD (n=17)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCD/UC=14/3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAge in years, (median, range)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e37 [19 - 68]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSexe ratio (H/F)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eYears from IBD to AA\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eamyloidosis\u003c/strong\u003e\u003cstrong\u003e(median, range)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 [0 - 25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDisease-related complications, n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePerianal disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eExtra-intestinal manifestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory parameters, (median, range)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSerum creatinine (µmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e98 [39–1207]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eeGFR (mL/min/1.73 m²)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57.4 [4.4–247.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal serum protein (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e47 [28–68]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSerum albumin (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19 [5.4–34]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCRP (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28 [16–84]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eProteinuria (g/24h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.2 [3.12–20.7]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical entities, n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNephrotic syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eImpaired renal function\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBiopsies performed, n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMinor Salivary gland biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRenal biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIBD - Inflammatory bowel disease; CD - Crohn disease; UC - Ulcerative colitis;\u0026nbsp;eGFR\u0026nbsp;-\u0026nbsp;estimated glomerular filtration rate; CRP - C-reactive protein.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Therapeutic management and outcomes of AA amyloidosis in patients with inflammatory bowel disease\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAA amyloidosis in IBD (n=17)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCD/UC=14/3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD therapy, n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSystemic steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5-aminosalicylic-acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAzathioprine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAnti-TNF-α\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD related surgery, n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAA\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eamyloidosis therapy, n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSystemic steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eColchicine use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAnti-TNF-α\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eESKD, n\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIBD - Inflammatory bowel disease; CD - Crohn disease; UC - Ulcerative colitis; TNF - tumor necrosis factor; ESKD - End stage kidney disease.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Crohn’s disease, Ulcerative colitis, Amyloidosis, Renal involvement","lastPublishedDoi":"10.21203/rs.3.rs-8925868/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8925868/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eRenal amyloidosis related to serum amyloid A (AA amyloidosis) is a rare but severe complication of inflammatory bowel disease (IBD), associated with significant renal morbidity; this study aimed to describe its clinical features, management, and renal outcomes in a multicenter cohort.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We conducted a retrospective study across two tertiary referral nephrology centers including patients with IBD and renal AA amyloidosis. Data were collected from 1990 to 2022 in the nephrology department of Charles Nicolle hospital Tunis and from 2008 to 2022 in the nephrology department of Sahloul hospital Sousse.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eSeventeen patients with IBD : 14 with Crohn’s disease and 3 with ulcerative colitis were included. The median age at diagnosis was 37 years [range: 19–68], with a male predominance. The median interval between IBD diagnosis and detection of renal involvement was 3 years. All patients had heavy proteinuria (\u0026gt;3 g/24 h), with nephrotic syndrome in 15 patients. Reduced kidney function was observed in eight patients. Diagnosis was established by minor salivary gland biopsy in 10 patients and by renal biopsy in seven. Nine patients continued previous IBD therapy, five received colchicine, two systemic corticosteroids, and one anti–TNF-α therapy. Renal outcomes were poor. One patient was dialysis-dependent at baseline, and eight patients progressed to end-stage kidney disease requiring dialysis over a median time of 19 months.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Renal AA amyloidosis represents a serious complication of IBD with poor renal prognosis. Early diagnosis and optimal control of intestinal inflammation are essential to prevent irreversible kidney damage.\u003c/p\u003e","manuscriptTitle":"Renal AA Amyloidosis Associated with Inflammatory Bowel Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-18 08:27:25","doi":"10.21203/rs.3.rs-8925868/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-26T07:06:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-24T23:33:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-14T20:05:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30669248338173988874000533386927251520","date":"2026-03-14T19:34:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117670451437708678026839876108192212055","date":"2026-03-13T20:16:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-12T16:42:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-12T16:37:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-02T06:34:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-28T14:56:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2026-02-28T14:27:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9d223329-1fbe-4ae4-b112-7937ea587142","owner":[],"postedDate":"March 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-06T06:55:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-18 08:27:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8925868","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8925868","identity":"rs-8925868","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}