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Jeon H, Park Y, Lee JJ, Suh YS, Kwok SK, Park SH, Kim WU, Koh JH. The prevalence, clinical features, and long-term outcome of patients with primary Sjögren's syndrome with renal involvement. Sci Rep 2025; 15:4211. [PMID: 39905236 PMCID: PMC11794661 DOI: 10.1038/s41598-025-88368-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 01/28/2025] [Indexed: 02/06/2025] Open
Abstract
This multicenter, retrospective longitudinal study identified primary Sjögren's syndrome (pSS) patients with clinically significant renal involvement, and analyzed factors associated with predisposition. To investigate clinical features and long-term prognosis of renal involvement, we compared the clinical outcomes for the entire cohort based on the presence or absence of renal involvement. Among 1306 pSS patients (mean age, 51 ± 12 years; 98% female), 36 (2.8%) had renal involvement; 17 patients had tubular involvement, 15 had glomerular involvement, one had both, and 3 were unclassified. The presence of anti-La antibodies was associated with renal involvement. Over the median 5-year follow-up period, the renal function did not change significantly; however, 44% of patients with renal involvement showed impaired renal function at the last visit. Impaired renal function at the last visit was inversely associated with baseline renal function and hemoglobin levels. Among the entire cohort, the prevalence of lymphoproliferative disease (LPD) was significantly higher in pSS patients with renal involvement than those without. Renal involvement is a rare manifestation of pSS; however, it is associated with impaired renal function and LPD. Therefore, screening for renal involvement is important for preserving renal function and early detection of LPD.
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Affiliation(s)
- Howook Jeon
- Division of Rheumatology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Youngjae Park
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jennifer Jooha Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoo-Seok Suh
- Division of Rheumatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung-Ki Kwok
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung-Hwan Park
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Wan-Uk Kim
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Hee Koh
- Division of Rheumatology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Tsuyuki T, Kitamura M, Takatani M, Tsuji K, Torigoe K, Tsuji S, Fujita N, Yamaguchi Y, Mukae H, Nishino T. Simultaneous Presentation of Minimal Change Disease and Tubulointerstitial Nephritis Associated with Primary Sjögren's Syndrome and Hashimoto's Thyroiditis: A Case Report. Intern Med 2025:4747-24. [PMID: 39894500 DOI: 10.2169/internalmedicine.4747-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2025] Open
Abstract
A 78-year-old woman experienced systemic edema and was diagnosed with nephrotic syndrome and Hashimoto's thyroiditis (HT). A renal biopsy revealed minimal change disease (MCD) and tubulointerstitial nephritis, which resulted in the diagnosis of primary Sjögren's syndrome (PSS). PSS and HT can be complicated with MCD; however, there are no published case reports of MCD presenting with both conditions simultaneously. We aimed to inform nephrologists and rheumatologists about this rare condition through a literature review of renal outcomes in patients with MCD associated with PSS and HT.
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Affiliation(s)
- Tomohisa Tsuyuki
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
- Department of Nephrology, Nagasaki Genbaku Hospital, Japan
| | - Mineaki Kitamura
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Miho Takatani
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Kiyokazu Tsuji
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Kenta Torigoe
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Sosuke Tsuji
- Department of Rheumatology, Nagasaki Genbaku Hospital, Japan
| | - Naruhiro Fujita
- Department of Endocrinology, Nagasaki Genbaku Hospital, Japan
| | | | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Tomoya Nishino
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
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Qiu DD, Li Z, Wang JJ, Chen DQ, Tu YM, Liang SS, Xu F, Liang DD, Zhang T, Cheng Z. The spectrum and prognosis of Sjögren's syndrome with membranous nephropathy. Clin Kidney J 2025; 18:sfae384. [PMID: 39927251 PMCID: PMC11806635 DOI: 10.1093/ckj/sfae384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Indexed: 02/11/2025] Open
Abstract
Background This study aims to investigate the spectrum and prognosis of membranous nephropathy (MN) in patients with Sjögren's syndrome (SS). Methods SS patients with biopsy-proven kidney involvement who were diagnosed at our center between April 2007 and February 2024 were retrospectively reviewed and analyzed. Results A total of 290 SS patients with kidney involvement were enrolled. The frequency of MN increased from 16.28% during the 2007-2010 period to 44.05% during the 2021-2024 period. After 2016, MN became the most common renal pathologic type, surpassing tubulointerstitial nephritis. PLA2R antibody or antigen was detected in 74 SS-MN patients, in whom 37 (50%) showed a negative result. Within the PLA2R-negative group, five out of 15 showed positivity for EXT1/EXT2 antigen and one out of eight for THSD7A antigen. Sixty-one SS patients with MN were followed up for >6 months, and 44 (72.13%) of them achieved renal complete remission (CR). Compared with PLA2R-negative patients, PLA2R-positive patients spent a longer time to achieve CR (1.46 ± 1.16 vs. 0.74 ± 0.47 years, P = .015) and had a higher rate of progression to the renal endpoint (8/32 vs. 1/29, P = .028). After adjusting for age, proteinuria, and eGFR, Cox regression analysis showed that PLA2R positivity remained a risk factor for CR [HR = 0.511, 95% CI (0.262 to 0.998), P = .049]. Conclusions MN has become the predominant renal pathologic type in SS. PLA2R-positivity testing followed by EXT1/EXT2 and THSD7A testing is recommended for SS-MN patients. Although most patients can achieve renal CR, the prognosis is usually poor in PLA2R-positive SS-MN patients.
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Affiliation(s)
- Dan-dan Qiu
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Zhi Li
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Jing-jing Wang
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Du-qun Chen
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Yuan-mao Tu
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Shao-shan Liang
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Feng Xu
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Dan-dan Liang
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Ti Zhang
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
| | - Zhen Cheng
- National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing, China
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Zeng Y, Liu R, Li S, Wei J, Luo F, Chen Y, Zhou D. Analysis of risk factors and development of a nomogram prediction model for renal tubular acidosis in primary Sjogren syndrome patients. Arthritis Res Ther 2024; 26:151. [PMID: 39175019 PMCID: PMC11340110 DOI: 10.1186/s13075-024-03383-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 08/05/2024] [Indexed: 08/24/2024] Open
Abstract
OBJECTIVE To investigate the risk factors of renal tubular acidosis (RTA) in patients with primary Sjögren's syndrome (pSS) and create a personalized nomogram for predicting pSS-RTA patients. METHOD Data from 99 pSS patients who underwent inpatient treatment at our hospital from January 2012 to January 2024 were retrospectively collected and analyzed. Bootstrap resampling technique, single-factor, and multi-factor logistic regression analyses were used to explore the risk factors for pSS-RTA. A nomogram was developed based on the results of the multivariate logistic model. The model was evaluated through receiver operating characteristic curve, C-index, calibration curve, and decision curve analysis. In addition, we graded the severity of pSS-RTA patients and used univariate analysis to assess the relationship between pSS-RTA severity and risk factors. RESULTS A multivariate logistic regression analysis revealed that concurrent thyroid disease, long symptom duration, subjective dry mouth, and positive RF were independent risk factors for pSS-RTA patients. Based on them, a personalized nomogram predictive model was established. With a p-value of 0.657 from the Hosmer-Lemeshow test, the model demonstrated a good fit. The AUC values in the training and validation groups were 0.912 and 0.896, indicating a strong discriminative power of the nomogram. The calibration curves for the training and validation groups closely followed the diagonal line with a slope of 1, confirming the model's reliable predictive ability. Furthermore, the decision curve analysis showed that the nomogram model had a net benefit in predicting pSS-RTA, emphasizing its clinical value.This study did not find an association between the severity of pSS-RTA and risk factors. DISCUSSION We developed a nomogram to predict RTA occurrence in pSS patients, and it is believed to provide a foundation for early identification and intervention for high-risk pSS patients.
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Affiliation(s)
- Yanzhen Zeng
- The First Clinical College, Xuzhou Medical University, Jiangsu Province, China
| | - Runzhi Liu
- The First Clinical College, Xuzhou Medical University, Jiangsu Province, China
| | - Shuyi Li
- The First Clinical College, Xuzhou Medical University, Jiangsu Province, China
| | - Jingwen Wei
- The First Clinical College, Xuzhou Medical University, Jiangsu Province, China
| | - Fei Luo
- The First Clinical College, Xuzhou Medical University, Jiangsu Province, China
| | - Yongkang Chen
- The First Clinical College, Xuzhou Medical University, Jiangsu Province, China
| | - Dongmei Zhou
- Rheumatology And Immunology Department, The Affiliated Hospital Of Xuzhou Medical University, Jiangsu Province, China.
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Esmeray Şenol P, Leventoğlu E, Öğüt B, Uzun Kenan B, Yıldız Ç. Lesson for the clinical nephrologist: proteinuria in a pediatric patient with dry mouth and polyarthritis. J Nephrol 2024; 37:799-802. [PMID: 37646986 DOI: 10.1007/s40620-023-01737-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/07/2023] [Indexed: 09/01/2023]
Affiliation(s)
- Pelin Esmeray Şenol
- Faculty of Medicine, Department of Pediatric Rheumatology, Gazi University, Ankara, Turkey.
| | - Emre Leventoğlu
- Faculty of Medicine, Department of Pediatric Nephrology, Gazi University, Ankara, Turkey
| | - Betül Öğüt
- Faculty of Medicine, Department of Pathology, Gazi University, Ankara, Turkey
| | | | - Çisem Yıldız
- Faculty of Medicine, Department of Pediatric Rheumatology, Gazi University, Ankara, Turkey
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Hamada S, Takata T, Yamada K, Yamamoto M, Mae Y, Iyama T, Sugihara T, Takata M, Isomoto H. Renal tubular acidosis without interstitial nephritis in Sjögren's syndrome: a case report and review of the literature. BMC Nephrol 2023; 24:237. [PMID: 37582721 PMCID: PMC10426178 DOI: 10.1186/s12882-023-03290-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 08/03/2023] [Indexed: 08/17/2023] Open
Abstract
BACKGROUND Renal tubular acidosis is the principal clinical feature associated with tubulointerstitial nephritis in patients with primary Sjögren's syndrome. Renal tubular dysfunction due to interstitial nephritis has been considered the underlying pathophysiology connecting renal tubular acidosis and primary Sjögren's syndrome. However, the detailed mechanisms underlying the pathophysiology of renal tubular acidosis in primary Sjögren's syndrome is not fully understood. CASE PRESENTATION A 30-year-old woman was admitted with complaints of weakness in the extremities. The patient was hospitalized thirteen years earlier for similar issues and was diagnosed with hypokalemic paralysis due to distal renal tubular acidosis with primary Sjögren's syndrome. This diagnosis was based on a positive Schirmer's test. Besides, anti-Sjögren's syndrome-related antigen A was also detected. Laboratory tests indicated distal RTA; however, a renal biopsy showed no obvious interstitial nephritis. Laboratory tests conducted during the second admission indicated distal renal tubular acidosis. Therefore, a renal biopsy was performed again, which revealed interstitial nephritis. Histological analysis of acid-base transporters revealed the absence of vacuolar type H+-ATPases in the collecting duct. The vacuolar type H+-ATPase was also absent in the past renal biopsy, suggesting that the alteration in acid-base transporters is independent of interstitial nephritis. CONCLUSIONS This case study demonstrates that vacuolar-type H+-ATPases are associated with distal renal tubular acidosis, and distal renal tubular acidosis precedes interstitial nephritis in patients with primary Sjögren's syndrome.
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Affiliation(s)
- Shintaro Hamada
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan
| | - Tomoaki Takata
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan.
| | - Kentaro Yamada
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan
| | - Marie Yamamoto
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan
| | - Yukari Mae
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan
| | - Takuji Iyama
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan
| | - Takaaki Sugihara
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan
| | - Miki Takata
- Department of Respiratory Medicine and Rheumatology Graduate School of Medicine, Tottori University Hospital, Yonago, Tottori, 683-8504, Japan
| | - Hajime Isomoto
- Division of Gastroenterology and Nephrology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan
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Brito-Zerón P, Flores-Chávez A, Horváth IF, Rasmussen A, Li X, Olsson P, Vissink A, Priori R, Armagan B, Hernandez-Molina G, Praprotnik S, Quartuccio L, Inanç N, Özkızıltaş B, Bartoloni E, Sebastian A, Romão VC, Solans R, Pasoto SG, Rischmueller M, Galisteo C, Suzuki Y, Trevisani VFM, Fugmann C, González-García A, Carubbi F, Jurcut C, Shimizu T, Retamozo S, Atzeni F, Hofauer B, Melchor-Díaz S, Gheita T, López-Dupla M, Fonseca-Aizpuru E, Giacomelli R, Vázquez M, Consani S, Akasbi M, Nakamura H, Szántó A, Farris AD, Wang L, Mandl T, Gattamelata A, Kilic L, Pirkmajer KP, Abacar K, Tufan A, de Vita S, Bootsma H, Ramos-Casals M, Sjögren Big Data Consortium arArendsS.TreppoE.LonghinoS.ManfrèV.RizzoM.BaldiniC.BombardieriS.BandeiraM.Silvéiro-AntónioM.SerorR.MarietteX.NordmarkG.DandaD.WilandP.GerliR.KwokS.K.ParkS.H.KvarnstromM.Wahren-HerleniusM.Downie-DoyleS.SeneD.IsenbergD.ValimV.Devauchelle-PensecV.SarauxA.MorelJ.MorcilloC.Díaz CuizaP.E.HerreraB.E.González-de-PazL.Sisó-AlmirallA.. Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study. EClinicalMedicine 2023; 61:102062. [PMID: 37457113 PMCID: PMC10344811 DOI: 10.1016/j.eclinm.2023.102062] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/07/2023] [Accepted: 06/09/2023] [Indexed: 07/18/2023] Open
Abstract
Background What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death. Interpretation The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding Novartis.
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Affiliation(s)
- Pilar Brito-Zerón
- Autoimmune Diseases Unit, Research and Innovation Group in Autoimmune Diseases, Sanitas Digital Hospital, Hospital-CIMA-Centre Mèdic Milenium Balmes Sanitas, Barcelona, Spain
| | | | - Ildiko Fanny Horváth
- Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Astrid Rasmussen
- Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
| | - Xiaomei Li
- Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, University of Science and Technology of China(Anhui Provincial Hosipital), Hefei, China
| | - Peter Olsson
- Department of Rheumatology, Skane University Hospital Malmö, Lund University, Lund, Sweden
| | - Arjan Vissink
- Department of Oral and Maxillofacial Surger, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
| | - Roberta Priori
- Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Rome, Italy
- Saint Camillus International University of Health Science, UniCamillus, Rome, Italy
| | - Berkan Armagan
- Division of Rheumatology, Department of Internal Medicine, Hacettepe University, Faculty of Medicine, Ankara, Turkey
| | - Gabriela Hernandez-Molina
- Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico
| | - Sonja Praprotnik
- Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia
| | - Luca Quartuccio
- Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital “Santa Maria della Misericordia”, Udine, Italy
| | - Nevsun Inanç
- Marmara University, School of Medicine, Istanbul, Turkey
| | - Burcugül Özkızıltaş
- Division of Rheumatology, Department of Internal Medicine, Gazi University School of Medicine, Ankara, Turkey
| | - Elena Bartoloni
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy
| | - Agata Sebastian
- Department of Rheumatology and Internal Medicine, Wroclaw Medical Hospital, Wroclaw, Poland
| | - Vasco C. Romão
- Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte and Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon Academic Medical Centre, Lisbon, Portugal
| | - Roser Solans
- Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
| | - Sandra G. Pasoto
- Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Maureen Rischmueller
- Department of Rheumatology, The Queen Elizabeth Hospital, Discipline of Medicine, University of Adelaide, South Australia, Australia
| | - Carlos Galisteo
- Department of Rheumatology, Hospital Parc Taulí, Barcelona, Spain
| | - Yasunori Suzuki
- Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
| | | | - Cecilia Fugmann
- Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Francesco Carubbi
- Internal Medicine and Nephrology Unit, Department of Medicine, ASL Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Ciprian Jurcut
- Department of Internal Medicine, Carol Davila Central Military Emergency Hospital, Bucharest, Romania
| | - Toshimasa Shimizu
- Division of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Soledad Retamozo
- Department of Rheumatology, Hospital Quirón Salud, Barcelona, Spain
| | - Fabiola Atzeni
- IRCCS Galeazzi Orthopedic Institute, Milan and Rheumatology Unit, University of Messina, Messina, Italy
| | - Benedikt Hofauer
- Otorhinolaryngology, Head and Neck Surgery, Technical University Munich, Munich, Germany
| | | | - Tamer Gheita
- Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt
| | | | | | - Roberto Giacomelli
- Clinical Unit of Rheumatology, University of l'Aquila, School of Medicine, L'Aquila, Italy
| | - Marcos Vázquez
- Department of Rheumatology, Hospital de Clínicas, San Lorenzo, Paraguay
| | - Sandra Consani
- Internal Medicine, Hospital Maciel, and Universidad de la República (UdelaR), Montevideo, Uruguay
| | - Miriam Akasbi
- Department of Internal Medicine, Hospital Infanta Leonor, Madrid, Spain
| | - Hideki Nakamura
- Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Antónia Szántó
- Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - A. Darise Farris
- Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
| | - Li Wang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, University of Science and Technology of China(Anhui Provincial Hosipital), Hefei, China
| | - Thomas Mandl
- Department of Rheumatology, Skane University Hospital Malmö, Lund University, Lund, Sweden
| | - Angelica Gattamelata
- Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Rome, Italy
| | - Levent Kilic
- Division of Rheumatology, Department of Internal Medicine, Hacettepe University, Faculty of Medicine, Ankara, Turkey
| | | | - Kerem Abacar
- Marmara University, School of Medicine, Istanbul, Turkey
| | - Abdurrahman Tufan
- Division of Rheumatology, Department of Internal Medicine, Gazi University School of Medicine, Ankara, Turkey
| | - Salvatore de Vita
- Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital “Santa Maria della Misericordia”, Udine, Italy
| | - Hendrika Bootsma
- Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain
- Department of Medicine, University of Barcelona, Barcelona, Spain
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8
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Chatterjee R, Balakrishnan A, Kharbanda R, Rathore U, Gupta L, Misra DP, Agarwal V, Aggarwal A, Lawrence A. Renal involvement in Sjőgren's syndrome: predictors and impact on patient outcomes. Rheumatol Int 2023; 43:1297-1306. [PMID: 36650312 DOI: 10.1007/s00296-022-05242-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 10/25/2022] [Indexed: 01/19/2023]
Abstract
Renal disease in primary Sjogren's Syndrome(pSS) occurs as tubulointerstitial nephritis(TIN) or glomerulonephritis(GN). Data from India on pSS are sparse and even less on nephritis.We studied the prevalence and impact of renal disease on patient outcomes. We reviewed 179 (F:M 12.7:1, age 41.7 ± 12.9 years) patients of pSS from records at a single centre from 2000 to 2020. Data on nephritis, clinical and laboratory variables were collected from baseline visit. Outcomes studied were chronic kidney disease(CKD) and death. We identified predictors of nephritis and rising creatinine on follow-up.Fifty-four (30.17%) patients had nephritis. Their mean age was 40.19 ± 13.28 years with 157.3 person-years follow-up. Vasculitis (OR 2.33, 1.02-5.3), fatigue (OR 3.29, 1.63-6.65), ANA positivity (OR 7.79, 1-60.62), anti-Ro52 (OR 2.74, 1.18-6.39), anti-La (OR 2.13, 1.1-4.14), both Ro and La (OR 2.4, 1.23-4.69) and lymphopenia (OR 2.27, 1.16-4.41) predicted nephritis on univariate analysis. On multivariate analysis, only fatigue (OR 2.83, 1.22-6.57) and an interaction between polyarthritis and vasculitis (OR 9.17, 1.15-72.96) was associated with nephritis. Creatinine at one (1.6 ± 1.17 mg/dL vs. 0.8 ± 0.2 mg/dL) and 2 years (1.62 ± 1.19 mg/dL vs. 0.8 ± 0.2 mg/dL) follow-up was higher in the nephritis group. Baseline haematuria, leukocyturia, 24 h urinary protein and thrombocytopenia were independent predictors of rising creatinine. Six patients died and 10 developed CKD. Event-free (death or CKD) survival was 89.1% at 5 years. Patients with nephritis had worse event-free survival.Our cohort had a younger age of onset of Sjogren's syndrome and a higher prevalence of nephritis than previously reported. Fatigue, polyarthritis and vasculitis at baseline predicted the development of nephritis. Nephritis was associated with a higher probability of death or CKD.
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Affiliation(s)
- Rudrarpan Chatterjee
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Anu Balakrishnan
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Rajat Kharbanda
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Upendra Rathore
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Latika Gupta
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Durga P Misra
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Vikas Agarwal
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Amita Aggarwal
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Able Lawrence
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
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9
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Krishnamurthy H, Yang Y, Song Q, Krishna K, Jayaraman V, Wang T, Bei K, Rajasekaran JJ. Evaluation of renal markers in systemic autoimmune diseases. PLoS One 2023; 18:e0278441. [PMID: 37352246 PMCID: PMC10289317 DOI: 10.1371/journal.pone.0278441] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 05/29/2023] [Indexed: 06/25/2023] Open
Abstract
Renal involvement is a common occurrence in subjects with systemic autoimmune diseases. The renal manifestation and its severity depend on the underlying condition and may reversely complicate the clinical course of autoimmune diseases. Renal function markers have been widely used in the assessment of normal functioning of kidneys including glomerular filtration rate and concentrating and diluting capacity of the kidney. An increase or decrease in the values of these markers may indicate kidney dysfunction. In this study, a number of critical renal markers were examined in seropositive autoimmune diseases including systemic lupus erythematosus (SLE), connective tissue disorder (CTD), and rheumatoid arthritis (RA). The data from three cohorts of subjects enrolled in renal markers and autoimmune antibody testing between January 2015 to August 2019 were retrospectively studied. The prevalence of renal markers that were out of the reference range and their average levels in female and male subgroups across SLE, CTD, and RA cohorts were compared and analyzed. The levels of renal markers are significantly affected by the presence of autoantibodies, in particular eGFR, cystatin C, and albumin. Autoantibodies were also more frequent in subjects with severe renal function damage. Close follow-up of both renal markers and autoantibodies may potentially assist in the early diagnosis of kidney diseases and improve the survival and life expectancy of autoimmune patients.
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Affiliation(s)
| | - Yuanyuan Yang
- Vibrant America LLC., San Carlos, CA, United States of America
| | - Qi Song
- Vibrant America LLC., San Carlos, CA, United States of America
| | - Karthik Krishna
- Vibrant America LLC., San Carlos, CA, United States of America
| | | | - Tianhao Wang
- Vibrant America LLC., San Carlos, CA, United States of America
| | - Kang Bei
- Vibrant America LLC., San Carlos, CA, United States of America
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10
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Choi J, Lee TW, Bae E, Jang HN, An HJ, Chang SH, Park DJ. IgA nephropathy with minimal change disease associated with primary Sjögren's syndrome: A case report. Medicine (Baltimore) 2023; 102:e33892. [PMID: 37266627 PMCID: PMC10238049 DOI: 10.1097/md.0000000000033892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/10/2023] [Accepted: 05/10/2023] [Indexed: 06/03/2023] Open
Abstract
RATIONALE Only 1 case of IgA nephropathy (IgAN) with minimal change disease (MCD) associated with primary Sjögren's syndrome (SS) has been reported. We additionally describe IgAN with MCD associated with primary SS. PATIENT CONCERNS A 80-year-old woman visited our hospital complaining of generalized edema that had started 4 weeks prior. She reported a sense of thirst and dry eye for the last 5 years. DIAGNOSES Her initial laboratory findings were compatible with nephrotic syndrome; both the antinuclear antibody (1:80) and anti-SS-A (Ro) antibody (200 U/mL) tests were positive. A salivary gland scan revealed markedly decreased uptake for both the parotid and submandibular glands. The Schirmer test was positive. The random urine protein/creatinine ratio was 10 mg/mg. Renal biopsy was compatible with IgAN with superimposed MCD. INTERVENTIONS Furosemide was intravenously administered with intermittent albumin infusion for her edema control. She was started on prednisone 40mg daily for 6 weeks, which was tapered to 5 mg for another 6 months after starting prednisolone. OUTCOMES Over the next 6 months, her edema improved and the proteinuria decreased significantly. LESSONS Physician should suspect IgA with MCD when patient with SS clinically showed nephrotic syndrome, and perform renal biopsy for pathologically diagnosis and appropriate treatment.
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Affiliation(s)
- Jungyoon Choi
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, South Korea
| | - Tae Won Lee
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, South Korea
| | - Eunjin Bae
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, South Korea
- Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, South Korea
- Institute of Health Science, Gyeongsang National University, Jinju, South Korea
| | - Ha Nee Jang
- Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Hyo Jung An
- Institute of Health Science, Gyeongsang National University, Jinju, South Korea
- Department of Pathology, Gyeongsang National University Changwon Hospital, Changwon, South Korea
- Department of Pathology, Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Se-Ho Chang
- Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, South Korea
- Institute of Health Science, Gyeongsang National University, Jinju, South Korea
- Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Dong Jun Park
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, South Korea
- Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, South Korea
- Institute of Health Science, Gyeongsang National University, Jinju, South Korea
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11
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Predisposing Factors, Clinical Picture, and Outcome of B-Cell Non-Hodgkin’s Lymphoma in Sjögren’s Syndrome. IMMUNO 2022. [DOI: 10.3390/immuno2040037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Among other systemic autoimmune diseases, primary Sjögren syndrome (pSS) bears the highest risk for lymphoma development. In pSS, chronic antigenic stimulation gradually drives the evolution from polyclonal B-cell expansion to oligoclonal/monoclonal B-cell predominance to malignant B-cell transformation. Thus, most pSS-related lymphomas are B-cell non-Hodgkin lymphomas (NHLs), with mucosa-associated lymphoid tissue (MALT) lymphomas predominating, followed by diffuse large B-cell lymphomas (DLBCLs) and nodal marginal zone lymphomas (NMZLs). Since lymphomagenesis is one of the most serious complications of pSS, affecting patients’ survival, a plethora of possible predisposing factors has been studied over the years, ranging from classical clinical, serological, hematological, and histological, to the more recently proposed genetic and molecular, allowing clinicians to timely detect and to closely follow-up the subgroup of pSS patients with increased risk for lymphoma development. Overall predisposing factors for pSS-related lymphomagenesis reflect the status of B-cell hyperactivity. Different clinical features have been described for each of the distinct pSS-related B-cell NHL subtypes. While generally pSS patients developing B-cell NHLs display a fairly good prognosis, outcomes in terms of treatment response and survival rates seem to differ depending on the lymphoma subtype, with MALT lymphomas being characterized by a rather indolent course and DLBCLs gravely affecting patients’ survival.
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12
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Stergiou IE, Bakasis AD, Giannouli S, Voulgarelis M. Biomarkers of lymphoma in Sjögren's syndrome: what's the latest? Expert Rev Clin Immunol 2022; 18:1155-1171. [PMID: 36097855 DOI: 10.1080/1744666x.2022.2123794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease standing in the crossroads of autoimmunity and lymphomagenesis, characterized by chronic B-cell hyperactivity and ectopic lymphoid tissue neoformation, potentially driving lymphoid malignant transformation. Lymphoma development is considered the most serious complication of pSS. AREAS COVERED: “ Old-classical" biomarkers (clinical, serological, hematological, and histological) validated in the past are analyzed under the perspective of recently published research. Biomarkers that have emerged during the last decade are subdivided to "old-new" and "newly proposed-novel" ones, including biomarkers pathophysiologically related to B-cell differentiation, lymphoid organization, and immune responses, identified in serum and tissue, both at genetic and protein level. Upcoming new imaging biomarkers, promising for further patient stratification, are also analyzed. EXPERT OPINION Salivary gland enlargement and cryoglobulinemia still remain the best validated "classical-old" biomarkers for lymphoma development. Though new biomarkers still need to be validated, some can be used for the identification of high-risk patients long before lymphoma diagnosis, some might be more relevant in distinct age subgroups, while others have an added value in the assessment of lymphoma remission or relapse. Future development of composite indices integrating old and recently proposed biomarkers could contribute to a more precise lymphoma prediction model.
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Affiliation(s)
- Ioanna E Stergiou
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Athanasios-Dimitrios Bakasis
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Stavroula Giannouli
- Hematology Unit, Second Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Michael Voulgarelis
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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13
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Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal). Adv Rheumatol 2022; 62:18. [PMID: 35650656 DOI: 10.1186/s42358-022-00248-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 05/15/2022] [Indexed: 11/10/2022] Open
Abstract
Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.
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14
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Muthuppalaniappan VM, Ball S. Acute Tubulointerstitial Nephritis. PRIMER ON NEPHROLOGY 2022:585-597. [DOI: 10.1007/978-3-030-76419-7_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
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15
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Furqan S, Banu S, Ram N. Osteoporosis Complicating Renal Tubular Acidosis in Association With Sjogren's Syndrome. Cureus 2021; 13:e18373. [PMID: 34725619 PMCID: PMC8554731 DOI: 10.7759/cureus.18373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2021] [Indexed: 11/05/2022] Open
Abstract
Chronic metabolic acidosis increases alkali mobilization from the bone and promotes the development of osteoporosis. We report the case of a 35-year-old Caucasian female who presented for surgical fixation of a left femoral fracture sustained six months previously from a ground level fall with known primary hypothyroidism (for 12 years, on thyroxine replacement) with history of hypokalemia for the last 13 years (on regular oral potassium supplements). There was no history of fracture in past. There was no history of renal stones. There was positive history of hypokalemic periodic paralysis twice in past (12 and 13 years back). There was no history of recurrent oral or ocular ulcers. On examination there was no uveitis, oral ulcers, lacrimal or parotid gland enlargement. Upon workup the patient was diagnosed with left-sided femur fracture (neck) and was admitted for surgical management. She underwent left dynamic hip screw fixation under general anesthesia which she tolerated well. Upon further workup she had normal anion gap with hyperchloremic metabolic acidosis, low vitamin D level and dual-energy x-ray absorptiometry (DEXA) scan revealed osteoporosis at femur and hip joint. Vitamin D was replaced, she was started on Ibandronate and calcium supplements. Her further workup revealed positive anti-SSA. Our final clinical diagnosis in this case is possible or incomplete Sjogren's syndrome causing type-1 renal tu-bular acidosis (RTA; distal RTA) with osteoporosis.
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Affiliation(s)
- Saira Furqan
- Endocrinology, Aga Khan University Hospital, Karachi, PAK
| | - Sabiha Banu
- Endocrinology, Aga Khan University Hospital, Karachi, PAK
| | - Nanik Ram
- Endocrinology, Aga Khan University Hospital, Karachi, PAK
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16
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Chen R, Wang J, Xie Q, Xue J, Hao C. Sjögren's syndrome complicated with membranous nephropathy, a cause or coincidence? Int J Rheum Dis 2021; 24:1086-1094. [PMID: 34223708 DOI: 10.1111/1756-185x.14168] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 04/25/2021] [Accepted: 06/13/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Sjögren's syndrome (SS) has been a well-documented cause of secondary membranous nephropathy (MN); however, the prevalence is quite low. Since primary MN is also a common disease in middle age, whether MN is secondary to SS or just coincidence remains uncertain. The detection of phospholipase A2 receptor (PLA2R), which is most often positive in idiopathic MN, has been rarely reported in such cases. METHODS We retrospectively studied 13 cases diagnosed with MN and SS in Huashan Hospital between 2009 and 2020, and performed PLA2R detection. We also review the literature by searching in the PubMed database. RESULTS Among the 13 patients, 8 were found to be PLA2R-positive and 5 were negative. Nine patients were female. All but 1 patients had normal renal function at the time of biopsy. All patients showed positive anti-nuclear antibody and anti-SSA. Two of the 8 PLA2R-positive patients showed positive anti-SSB and 1/8 had mild hypocomplementemia, while all 5 PLA2R-negative patients had positive anti-SSB and 3 showed hypocomplementemia. Renal biopsy revealed focal MN and markedly mesangial hyperplasia in PLA2R-negative patients. Mesangial electron deposits were observed in 1 PLA2R-positive patient in small amounts, and in 3 PLA2R-negative patients with 2 in large amounts. During follow-up, 2 patients in the PLA2R-negative group presented with progressively decreasing serum complement levels, and another one was diagnosed with systemic lupus erythematosus (SLE). CONCLUSIONS In patients with both MN and SS, PLA2R-negative MN should be considered as a secondary form. Careful screen for SLE is necessary in these patients during follow-up.
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Affiliation(s)
- Ruiying Chen
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jia Wang
- Division of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Qionghong Xie
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jun Xue
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Chuanming Hao
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
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17
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Normo-Calcemic Tetany in a Patient with Hypokalemic Periodic Paralysis of Sjogren’s Syndrome: Neuromuscular Excitability Secondary to the ‘Forgotten Cation’. ARCHIVES OF NEUROSCIENCE 2021. [DOI: 10.5812/ans.105542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
: A young lady, a known case of Sjogren’s syndrome, presented to our hospital with hypokalemic flaccid paralysis requiring ventilatory support. She was investigated and found to have severe hypokalemia and metabolic acidosis. During her hospitalization, she had severe persistent carpopedal spasm with normal ionized calcium. Following further evaluation, there was evidence of hypomagnesemia. The spasms were improved after her hypomagnesemia was corrected. This case report illustrate the role of hypomagnesemia in neurological abnormalities in hospitalized patients.
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18
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Ranaweerage R, Perera S, Gunapala A. Hypokalaemic paralysis and metabolic alkalosis in a patient with Sjögren syndrome: a case report and literature review. BMC Nephrol 2021; 22:159. [PMID: 33931020 PMCID: PMC8086307 DOI: 10.1186/s12882-021-02371-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 04/22/2021] [Indexed: 11/21/2022] Open
Abstract
Background Acquired Gitelman syndrome is a very rare disorder reported in association with autoimmune disorders, mostly Sjögren syndrome. It is characterized by the presence of hypokalaemic metabolic alkalosis, hypocalciuria, hypomagnesaemia and hyper-reninaemia, in the absence of typical genetic mutations associated with inherited Gitelman syndrome. Case presentation A 20 year old woman who was previously diagnosed with primary Sjögren syndrome and autoimmune thyroiditis presented with two week history of lower limb weakness and salt craving. Examination revealed upper limb and lower limb muscle weakness with muscle power of 3/5 on MRC scale and diminished deep tendon reflexes. On evaluation, she had hypokalaemia with high trans-tubular potassium gradient, metabolic alkalosis and hypocalciuria, features suggestive of Gitelman syndrome. New onset hypokalaemic alkalosis in a previously normokalaemic patient with Sjögren syndrome strongly favored a diagnosis of acquired Gitelman syndrome. Daily potassium supplementation and spironolactone resulted in complete clinical recovery. Conclusions Acquired Gitelman syndrome associated with Sjögren syndrome is rare. It should be considered as a differential diagnosis during evaluation of acute paralysis and hypokalaemic metabolic alkalosis in patients with autoimmune disorders, especially Sjögren syndrome. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-021-02371-5.
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Affiliation(s)
| | - Shehan Perera
- General medicine, National Hospital of Sri Lanka, Colombo, Sri Lanka
| | - Aruna Gunapala
- General medicine, National Hospital of Sri Lanka, Colombo, Sri Lanka
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19
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Aiyegbusi O, McGregor L, McGeoch L, Kipgen D, Geddes CC, Stevens KI. Renal Disease in Primary Sjögren's Syndrome. Rheumatol Ther 2020; 8:63-80. [PMID: 33367966 PMCID: PMC7991017 DOI: 10.1007/s40744-020-00264-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022] Open
Abstract
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterised by lymphocytic infiltration of the exocrine glands, predominantly the salivary and lacrimal glands, leading to sicca symptoms. Patients may have extraglandular disease involving multiple organs, including the kidneys. 5% of patients with pSS can have renal involvement. Kidney disease in pSS presents a diagnostic challenge, as clinical symptoms are often insidious and can precede sicca symptoms. pSS affects the kidney through lymphocytic infiltration of renal tubules or immune complex deposition, leading to an array of clinical features. Tubulointerstitial nephritis is the most common histological pattern of kidney disease. Other tubular injuries include renal tubular acidosis with hypokalaemia, Fanconi's syndrome and diabetes insipidus. Glomerular disease is less common and typically involves an immune complex-mediated process. Optimal treatment for kidney diseases in pSS is not established, and treatment is guided by the pattern of disease. For tubulointerstitial nephritis, management involves electrolyte imbalance correction and the use of immunosuppression, including steroids. Treatment of glomerular disease is targeted to the histological pattern, and often requires a combination of immunosuppressive agents. The risk of end-stage kidney disease is low. Nevertheless, patients with pSS and kidney disease have significantly reduced quality of life.
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Affiliation(s)
- Oshorenua Aiyegbusi
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Teaching Hospital, Glasgow, UK.
| | | | | | - David Kipgen
- Pathology Department, Queen Elizabeth University Teaching Hospital, Glasgow, UK
| | - Colin C Geddes
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Teaching Hospital, Glasgow, UK
| | - Kathryn I Stevens
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Teaching Hospital, Glasgow, UK
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20
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Hong R, Xu D, Hsieh E, Xiang Y, Zhao J, Wang Q, Tian X, Li M, Zhao Y, Zeng X. Factors Associated With Renal Involvement in Primary Sjögren's Syndrome: A Meta-Analysis. Front Med (Lausanne) 2020; 7:614482. [PMID: 33324667 PMCID: PMC7726424 DOI: 10.3389/fmed.2020.614482] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 10/29/2020] [Indexed: 11/29/2022] Open
Abstract
Background: Renal impairment is a critical complication in primary Sjögren's syndrome (pSS), resulting in chronic renal disease and even death. This meta-analysis was designed to find out the relevant factors of renal involvement in pSS. Methods: PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science were systemically searched until August 30, 2019. Studies were selected according to inclusion criteria, and data was extracted by two researchers independently. The Newcastle-Ottawa Scale was applied for quality assessment. Random- and fixed-effects models were used in this meta-analysis based on the result of the heterogeneity test. Meanwhile, a sensitivity analysis was conducted to investigate the cause of heterogeneity. Publication bias was shown in the funnel plot and evaluated further by Begg's and Egger's tests. Results: Of the 9,989 articles identified, five articles enrolling 1,867 pSS patients were included in the final analysis, 533 with and 1,334 without renal involvement. There was no statistical significance in age and gender between these two groups. According to the meta-analysis, anti-SSB antibody, and arthralgia showed a significant association with renal involvement in pSS, the overall odds ratio (OR) values of which were 1.51 (95% CI, 1.16–1.95) and 0.59 (95% CI, 0.46–0.74), respectively. On the other hand, the overall OR values of anti-SSA antibody, rheumatoid factor, dry eyes, and labial salivary gland biopsy were just 0.90 (95% CI, 0.49–1.64), 1.05 (95% CI, 0.59–1.86), 0.60 (95% CI, 0.34–1.06), and 1.38 (95% CI, 0.98–1.95), respectively. Conclusion: The presence of anti-SSB antibody is positively associated with renal involvement in pSS, while arthralgia is inversely associated. Large-scale prospective cohort studies are needed in the future to identify further risk factors.
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Affiliation(s)
- Ruping Hong
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Dong Xu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Evelyn Hsieh
- Section of Rheumatology, Allergy and Immunology, Yale University School of Medicine, New Haven, CT, United States
| | - Yirong Xiang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Jiuliang Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Qian Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xinping Tian
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Yan Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
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Abstract
Primary Sjögren syndrome is an autoimmune disorder characterized by lymphoplasmacytic infiltration of the exocrine (salivary and lachrymal) glands resulting in sicca symptoms (dryness). Systemic complications can occur in primary Sjögren syndrome, but renal involvement is rare, affecting<10% patients. The most frequent form of nephropathy in primary Sjögren syndrome is tubulointerstitial nephritis, where infiltration of the kidney by plasma cells is a key feature and shows similarity to the lymphoplasmacytic infiltration of the salivary glands. Electrolyte disturbances may occur in primary Sjögren syndrome, such as renal distal tubular acidosis, diabetes insipidus, Gitelman syndrome, or Fanconi syndrome. Glomerular involvement is less frequently detected in patients with primary Sjögren syndrome, but can take the form of membranoproliferative glomerulonephritis secondary to cryoglobulinaemia. The renal prognosis in patients with primary Sjögren syndrome and TIN or glomerular disease is usually good, but the risk of chronic kidney disease remains significant for some patients. Appropriate screening must be performed at least once a year in patients with systemic primary Sjögren syndrome in order to facilitate the early detection of renal complications. In this Review, we discuss the epidemiology, pathophysiology, differential diagnosis, and treatment of renal disease in primary Sjögren syndrome.
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Affiliation(s)
- Hélène François
- Département d'Urgences Néphrologiques et Transplantation Rénale, INSERM UMR_S 1155, Hôpital Tenon, Sorbonne université, AP-HP, Paris, France.
| | - Xavier Mariette
- Inserm, CEA, rheumatology department, centre de recherche en immunologie des infections virales et des maladies auto-immunes, université Paris-Saclay, hôpital Bicêtre, AP-HP, 94270 Le Kremlin-Bicêtre, France
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22
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Cortazar FB, Rhee EP, Gupta S, Sakhuja R, Stone JH, Colvin RB. Case 34-2020: A 74-Year-Old Man with Chronic Kidney Disease. N Engl J Med 2020; 383:1768-1778. [PMID: 33113299 DOI: 10.1056/nejmcpc2002415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Frank B Cortazar
- From the New York Nephrology Vasculitis and Glomerular Center and the Department of Medicine, St. Peter's Hospital - both in Albany (F.B.C.); and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Massachusetts General Hospital, and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Harvard Medical School - both in Boston
| | - Eugene P Rhee
- From the New York Nephrology Vasculitis and Glomerular Center and the Department of Medicine, St. Peter's Hospital - both in Albany (F.B.C.); and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Massachusetts General Hospital, and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Harvard Medical School - both in Boston
| | - Sumit Gupta
- From the New York Nephrology Vasculitis and Glomerular Center and the Department of Medicine, St. Peter's Hospital - both in Albany (F.B.C.); and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Massachusetts General Hospital, and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Harvard Medical School - both in Boston
| | - Rahul Sakhuja
- From the New York Nephrology Vasculitis and Glomerular Center and the Department of Medicine, St. Peter's Hospital - both in Albany (F.B.C.); and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Massachusetts General Hospital, and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Harvard Medical School - both in Boston
| | - John H Stone
- From the New York Nephrology Vasculitis and Glomerular Center and the Department of Medicine, St. Peter's Hospital - both in Albany (F.B.C.); and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Massachusetts General Hospital, and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Harvard Medical School - both in Boston
| | - Robert B Colvin
- From the New York Nephrology Vasculitis and Glomerular Center and the Department of Medicine, St. Peter's Hospital - both in Albany (F.B.C.); and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Massachusetts General Hospital, and the Departments of Medicine (F.B.C., E.P.R., R.S., J.H.S.), Radiology (S.G.), and Pathology (R.B.C.), Harvard Medical School - both in Boston
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Ramponi G, Folci M, Badalamenti S, Angelini C, Brunetta E. Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome. Front Immunol 2020; 11:562101. [PMID: 33042142 PMCID: PMC7527442 DOI: 10.3389/fimmu.2020.562101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 08/14/2020] [Indexed: 01/01/2023] Open
Abstract
Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and may affect several organs. Renal involvement has long been known as one of the systemic complications of pSS. The most classical lesion observed in pSS is tubulointerstitial nephritis (TIN) and less frequently membranoproliferative glomerulonephritis (MPGN), which is related to cryoglobulinemia. In some cases, renal biopsy is necessary for the definitive diagnosis of kidney involvement. Patients may present with proximal renal tubular acidosis, distal renal tubular acidosis and chronic kidney disease. Response to treatment is usually favorable. However, occasionally severe and rarely lethal outcomes have been described. Recently, several case series and cross-sectional studies have been published which investigated the factors associated with renal involvement in pSS and the most accurate screening tests for early detection. The presence of xerophthalmia, anti-SSA and rheumatoid factor positivity, low C3 levels and other features have all shown either positive or inverse associations with the development of renal complications. Serum creatinine, alpha-1-microglobulin, cystatin-C have been evaluated as early detection biomarkers with variable accuracy. More advanced techniques may be necessary to confirm proximal and distal renal tubular acidosis, along with nephrogenic diabetes insipidus. The aim of the current paper is to summarize and critically examine these findings in order to provide updated guidance on serum biomarkers and further testing for kidney involvement in pSS.
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Affiliation(s)
- Giacomo Ramponi
- Department of Nephrology, Humanitas Clinical and Research Center - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Marco Folci
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Internal Medicine and Hepatology, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - Salvatore Badalamenti
- Department of Nephrology, Humanitas Clinical and Research Center - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Claudio Angelini
- Department of Nephrology, Humanitas Clinical and Research Center - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Enrico Brunetta
- Department of Nephrology, Humanitas Clinical and Research Center - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
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24
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Rajan R, Cherian KE, Mathew J, Asha HS, Kapoor N, Paul TV. Beyond sicca symptoms: Osteomalacia secondary to renal tubular acidosis in Sjogren syndrome. Joint Bone Spine 2020; 88:105064. [PMID: 32952003 DOI: 10.1016/j.jbspin.2020.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/21/2020] [Indexed: 11/19/2022]
Affiliation(s)
- Remya Rajan
- Departments of Endocrinology, Christian Medical College, 632004 Vellore, India
| | | | - John Mathew
- Rheumatology, Christian Medical College, 632004 Vellore, India
| | | | - Nitin Kapoor
- Departments of Endocrinology, Christian Medical College, 632004 Vellore, India
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25
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Lin CY, Wu CH, Chen HA, Hsu CY, Wang LH, Su YJ. Long-term renal prognosis among patients with primary Sjögren's syndrome and renal involvement: A nationwide matched cohort study. J Autoimmun 2020; 113:102483. [PMID: 32446704 DOI: 10.1016/j.jaut.2020.102483] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/28/2020] [Accepted: 05/06/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND The long-term renal outcome in patients with primary Sjögren's syndrome (pSS) remains uncertain. We aimed to determine the absolute incidence and relative risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in patients with pSS at the general population level. METHODS We performed a retrospective cohort study using a national health insurance database in Taiwan from 2000 to 2013. We calculated the cumulative incidence of CKD and ESRD in our pSS and age-, sex- and entry time-matched control cohorts. Cox regression analyses were used to estimate adjusted hazard ratios (aHRs) after adjusting for comorbidities and medications. RESULTS Among 17 505 patients with incident pSS, 1008 (5.8%) developed CKD and 38 (0.22%) developed ESRD. Of the 87 525 non-pSS controls, 3173 (3.6%) developed CKD and 256 (0.29%) developed ESRD. The risk of CKD was higher in patients with pSS than in the non-pSS controls (adjusted hazard ratio [HR] 1.49, 95% confidence interval [95% CI] 1.38-1.59). Notably, the risk of ESRD was similar in both pSS and non-pSS cohorts (aHR 0.82, 95% CI 0.58-1.16). CONCLUSIONS Renal prognosis among patients with pSS and renal involvement is good. Although the risk of ESRD did not increase in patients with pSS, a significantly increased risk of CKD was observed in these patients, indicating the need for increased vigilance in regular monitoring for renal complications in patients with pSS.
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Affiliation(s)
- Chun-Yu Lin
- Division of Rheumatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Chun-Hsin Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Hung-An Chen
- Division of Allergy-Immunology-Rheumatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
| | - Chung-Yuan Hsu
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| | - Li-Hui Wang
- Division of Immunology, Department of Pediatrics, Kuo General Hospital, National Cheng Kung University Hospital, Tainan, Taiwan.
| | - Yu-Jih Su
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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26
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Luo J, Xu S, Lv Y, Huang X, Zhang H, Zhu X, Wang X. Clinical features and potential relevant factors of renal involvement in primary Sjögren's syndrome. Int J Rheum Dis 2019; 22:182-190. [PMID: 30411528 PMCID: PMC6587856 DOI: 10.1111/1756-185x.13429] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 08/27/2018] [Accepted: 10/04/2018] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To investigate distinct features of renal involvement in patients with primary Sjögren's syndrome (pSS) and to identify potential factors associated with renal involvement. METHODS Four hundred and thrity-four pSS patients from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University from 2013 to 2017 were included in a cross-sectional study. Patients with renal involvement were compared with their age- and gender-matched controls (pSS without renal involvement). Demographic, clinical, histological, nephritic, immunological features of renal involvement in pSS were systematically analyzed. Possible factors related to renal involvement were identified using multivariate logistic regression analyses. RESULTS One hundred and ninety-two pSS patients (88.48%) with renal involvement were women with mean age of nearly 58 years and mean disease duration of above 4 years. Clinical manifestation, serologic and immunological features and renal biopsy class of the pSS patients with renal involvement were presented. By multivariate analyses, xerophthalmia, histological positivity for lower salivary gland biopsy (LSGB), anti-SSA/Ro52-positive, reduced complement 3 (C3) levels, hypoalbuminemia and anemia retained significant association with renal involvement in pSS (all P < 0.05). CONCLUSION In addition to LSGB pattern, anti-SSA/Ro52-positivity, reduced C3 levels, hypoalbuminemia and anemia, also indicate significant association with renal involvement in pSS. Therefore, early vigilance is required for patients with these clinical manifestations.
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Affiliation(s)
- Jing Luo
- Rheumatology DepartmentThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Shihao Xu
- Department of UltrasonographyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Yinqiu Lv
- Rheumatology DepartmentThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Xinshi Huang
- Rheumatology DepartmentThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Huxiang Zhang
- Department of PathologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Xiaochun Zhu
- Rheumatology DepartmentThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Xiaobing Wang
- Rheumatology DepartmentThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
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27
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Skarlis C, Palli E, Nezos A, Koutsilieris M, Mavragani CP. Study of the incidence of osteoporosis in patients with Sjögren's syndrome (pSS) and investigation of activation of the RANKL /RANK and osteoprotegerin (OPG) system. Mediterr J Rheumatol 2018; 29:224-227. [PMID: 32185332 PMCID: PMC7045933 DOI: 10.31138/mjr.29.4.224] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 12/12/2018] [Indexed: 12/29/2022] Open
Affiliation(s)
| | | | | | - Michail Koutsilieris
- Department of Physiology.,Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
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28
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Goules AV, Tzioufas AG. Lymphomagenesis in Sjögren's syndrome: Predictive biomarkers towards precision medicine. Autoimmun Rev 2018; 18:137-143. [PMID: 30572133 DOI: 10.1016/j.autrev.2018.08.007] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 08/08/2018] [Indexed: 12/22/2022]
Abstract
Sjögren's syndrome (SS) is characterized by B cell hyperactivity documented by the production of plethora of autoantibodies and a strong tendency for NHL of B cell origin. Classical predictors of lymphoma have been already proposed and proved their validity, including clinical, serological and histopathologic biomarkers. The process of lymphomagenesis is multistep and encompasses mechanisms of antigen driven selection of the BCR with RF activity and various genetic contributors implicated in B cell proliferation, cell growth and cell cycle control, enhanced by a complex milieu of cytokines and trophic agents that are abundant within the inflammatory lesion of minor salivary glands of SS patients. Extensive efforts in the basic research field have revealed several novel biomarkers for lymphoma prediction while the major cellular and molecular mechanisms of evolutionary transition of B cells towards malignancy are under investigation. In this review, we present the current data regarding the newly proposed biomarkers for SS associated lymphoma prediction and a hypothetical model of lymphomagenesis based on the emerging data.
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Affiliation(s)
- Andreas V Goules
- Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, 115 27 Athens, Greece
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, Mikras Asias Str 75, 115 27 Athens, Greece.
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29
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Ugolini-Lopes MR, Santos LPS, Stagnaro C, Seguro LPC, Mosca M, Bonfá E. Late-onset biopsy-proven lupus nephritis without other associated autoimmune diseases: severity and long-term outcome. Lupus 2018; 28:123-128. [DOI: 10.1177/0961203318811603] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background/Purpose Lupus nephritis (LN) usually develops within the first years of systemic lupus erythematosus (SLE) onset and rarely after that. There are scarce studies comparing early- versus late-onset nephritis (before versus after five years of SLE diagnosis). The aim of this study was to compare the severity and long-term outcome (after 7 years) in these two, late-onset and early-onset, nephritis groups. Methods This study included 93 patients from rheumatology tertiary centers from Brazil and Italy, all of them with biopsy-proven LN with > 7 years follow-up. Patients were divided in two groups: early-onset nephritis ( n = 75) and late-onset nephritis ( n = 18). Clinical and laboratorial data were obtained using a standardized electronic chart database protocol carried out at 1–6 months interval and established in 2000. Patients >50 years or with concomitant autoimmune diseases were excluded. Variables evaluated at the LN presentation were Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), creatinine, albumin, anti-DNA positivity and nephritis class. Variables evaluated at the long-term outcome (after 7 years) were Systemic Lupus International Collaborating Clinics Damage Index (SDI), creatinine, dialysis and mortality. Results The average time of LN presentation was 10.94 ± 3.73 years for the late-onset and 1.20 ± 1.60 years for the early-onset group. Their similar nephritis duration (12.44 ± 3.2 versus 13.28 ± 4.03 years, p = 0.41) and comparable mean ages (49.17 ± 9.9 versus 44.11 ± 10.8 years old, p = 0.06) allow a more accurate comparison. Regarding severity, late-onset was similar to early-onset group: SLEDAI (8 (range: 6–22) versus 12 (range: 2–24), p = 0.47), creatinine (1.36 ± 0.94 versus 1.36 ± 1.13 mg/dl, p = 0.99); albumin (2.84 ± 0.65 versus 2.59 ± 0.84 mg/dl, p = 0.30); proteinuria (3.77 ± 2.18 versus 5.01 ± 4.51 g/vol, p = 0.26); proliferative nephritis (44% ( n = 8) versus 60% ( n = 45), p = 0.23). There was also no difference in the long-term outcomes between groups: SDI (1 (range: 0–5) versus 0.5 (range: 0–5), p = 0.27); creatinine (2.04 ± 2.38 versus 1.69 ± 2.26 mg/dl, p = 0.56); dialysis (22% ( n = 4) versus 13% ( n = 10), p = 0.46) and mortality (0% ( n = 0) versus 12% ( n = 9), p = 0.19). Conclusion This study provides novel evidence of comparable long-term outcomes between late-onset and early-onset nephritis, which is most likely explained by the observation that at presentation, the clinical, laboratorial and histological features of late-onset and early-onset nephritis are similar. This suggests that there should be no distinct treatment targets and therapeutic interventions for the late- and early-onset groups.
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Affiliation(s)
- M R Ugolini-Lopes
- Department of Rheumatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - L P S Santos
- Department of Rheumatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - C Stagnaro
- Rheumatology Unit, Department of Clinical and Experimental Medicine, Università di Pisa, Pisa, Italy
| | - L P C Seguro
- Department of Rheumatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - M Mosca
- Rheumatology Unit, Department of Clinical and Experimental Medicine, Università di Pisa, Pisa, Italy
| | - E Bonfá
- Department of Rheumatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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Abbas F, El Kossi M, Kim JJ, Shaheen IS, Sharma A, Halawa A. Complement-mediated renal diseases after kidney transplantation - current diagnostic and therapeutic options in de novo and recurrent diseases. World J Transplant 2018; 8:203-219. [PMID: 30370231 PMCID: PMC6201327 DOI: 10.5500/wjt.v8.i6.203] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 08/09/2018] [Accepted: 08/28/2018] [Indexed: 02/05/2023] Open
Abstract
For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy (a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable cases. Several less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.
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Affiliation(s)
- Fedaey Abbas
- Nephrology Department, Jaber El Ahmed Military Hospital, Safat 13005, Kuwait
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Jon Jin Kim
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Nottingham Children Hospital, Nottingham NG7 2UH, United Kingdom
| | - Ihab Sakr Shaheen
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Royal Hospital for Children, Glasgow G51 4TF, United Kingdom
| | - Ajay Sharma
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Sheffield Teaching Hospitals, Sheffield S57AU, United Kingdom
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Oliva-Damaso N, Oliva-Damaso E, Payan J. Acute and Chronic Tubulointerstitial Nephritis of Rheumatic Causes. Rheum Dis Clin North Am 2018; 44:619-633. [PMID: 30274627 DOI: 10.1016/j.rdc.2018.06.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Tubulointerstitial nephritis (TIN) is the second most common cause of acute intrinsic kidney injury after acute tubular necrosis. Although drug-induced forms of TIN represent the vast majority, rheumatic disease is another common cause and often underdiagnosed. Early diagnosis of acute interstitial nephritis and prompt withdrawal of the culprit medication or a correct treatment can avoid chronic damage and progressive chronic kidney disease. This review highlights the recent updates, clinical features, and treatment in TIN in autoimmune rheumatic disease.
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Affiliation(s)
- Nestor Oliva-Damaso
- Department of Medicine, Division of Nephrology, Hospital Costa del Sol, A-7, Km 187, 29305 Marbella, Malaga, Spain.
| | - Elena Oliva-Damaso
- Department of Medicine, Division of Nephrology, Hospital Doctor Negrin, Barranco de la Ballena, 35010 Las Palmas de Gran Canaria, Spain
| | - Juan Payan
- Department of Medicine, Division of Nephrology, Hospital Costa del Sol, A-7, Km 187, 29305 Marbella, Malaga, Spain
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32
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Jain A, Srinivas BH, Emmanuel D, Jain VK, Parameshwaran S, Negi VS. Renal involvement in primary Sjogren’s syndrome: a prospective cohort study. Rheumatol Int 2018; 38:2251-2262. [DOI: 10.1007/s00296-018-4118-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 08/02/2018] [Indexed: 12/19/2022]
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Morimoto C, Fujigaki Y, Tamura Y, Ota T, Shibata S, Asako K, Kikuchi H, Kono H, Kondo F, Yamaguchi Y, Uchida S. Emergence of Smoldering ANCA-associated Glomerulonephritis during the Clinical Course of Mixed Connective Tissue Disease and Sjögren's Syndrome. Intern Med 2018; 57:1757-1762. [PMID: 29269683 PMCID: PMC6047994 DOI: 10.2169/internalmedicine.9844-17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
A 67-year-old woman presented with hematuria and proteinuria 16 and 11 months ago, respectively. She had been followed up as mixed connective tissue disease and Sjögren's syndrome for over 19 years. Blood chemistry showed no elevated serum creatinine or C-reactive protein but did reveal myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) of 300 U/dL. A kidney biopsy showed pauci-immune focal necrotizing glomerulonephritis. She was treated with prednisolone and rituximab, resulting in normal urinalysis and decreased MPO-ANCA. The complication of ANCA-associated glomerulonephritis should not be overlooked when abnormal urinalysis findings appear in the course of connective tissue disease, irrespective of the presence of rapidly progressive glomerulonephritis.
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Affiliation(s)
- Chikayuki Morimoto
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Yoshihide Fujigaki
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
- Central Laboratory, Teikyo University School of Medicine, Japan
| | - Yoshifuru Tamura
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Tatsuru Ota
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Shigeru Shibata
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Kurumi Asako
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Hirotoshi Kikuchi
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Hajime Kono
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
| | - Fukuo Kondo
- Department of Pathology, Teikyo University School of Medicine, Japan
| | - Yutaka Yamaguchi
- Department of Pathology, Teikyo University School of Medicine, Japan
| | - Shunya Uchida
- Department of Internal Medicine, Teikyo University School of Medicine, Japan
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Yamanaka M, Fujigaki Y, Kono H, Nagura M, Arai S, Tamura Y, Ota T, Shibata S, Kondo F, Yamaguchi Y, Uchida S. A patient presenting with isolated hematuria and renal dysfunction as rare manifestation of cryoglobulinemic glomerulonephritis in the course of autoimmune diseases including Sjögren's syndrome. CEN Case Rep 2018; 7:211-216. [PMID: 29671215 DOI: 10.1007/s13730-018-0329-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 04/09/2018] [Indexed: 11/29/2022] Open
Abstract
Autoimmune diseases are sometimes associated with immune-mediated renal diseases and cryoglobulinemia is one of the causes. Cryoglobulinemia and cryoglobulinemic glomerulonephritis associated with primary Sjögren's syndrome are most frequent condition among non-hepatitis C virus-related condition. Its typical renal manifestation shows high amount of proteinuria with microscopic hematuria and renal insufficiency. We describe a case of 72-year-old woman with Hashimoto disease, autoimmune hepatitis, Sjögren's syndrome, and immune-related pancytopenia complicated by cryoglobulinemic glomerulonephritis. Before kidney biopsy, tubulointerstitial nephritis probably due to Sjögren's syndrome was suspected because of persistent hematuria without significant proteinuria and developing mild renal dysfunction over 6 months. The developing renal dysfunction associated with isolated hematuria is uncommon in glomerular diseases. Kidney biopsy, however, revealed established membranoproliferative glomerulonephritis with subendothelial deposits consisting of tubular structures with IgM, IgG, and C3 staining. Corticosteroids plus mycophenolate mofetil therapy successfully normalized renal function. Physician should not overlook cryoglobulinemic glomerulonephritis, which is potentially poor prognosis, even if urinalysis shows only persistent isolated hematuria in patients with autoimmune diseases.
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Affiliation(s)
- Masaki Yamanaka
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Yoshihide Fujigaki
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan.
| | - Hajime Kono
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Michito Nagura
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Shigeyuki Arai
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Yoshifuru Tamura
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Tatsuru Ota
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Shigeru Shibata
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Fukuo Kondo
- Department of Pathology, Teikyo University Hospital, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Yutaka Yamaguchi
- Department of Pathology, Teikyo University Hospital, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
| | - Shunya Uchida
- Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan
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Biopsy-proven renal involvement and prognosis in 13 hispanic patients with primary Sjögren syndrome. Med Clin (Barc) 2018; 150:43-48. [PMID: 28864093 DOI: 10.1016/j.medcli.2017.06.050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 05/29/2017] [Accepted: 06/01/2017] [Indexed: 11/23/2022]
Abstract
BACKGROUND The aim of this study was to describe a case series of 13 Hispanic patients with primary Sjögren syndrome (pSS) and biopsy-proven renal involvement. METHODS We describe the clinical, serological and histological characteristics as well as the prognosis in a group of patients with pSS and biopsy-proven renal involvement, treated in 2 referral nephrology units in Mexico City. RESULTS Thirteen patients with pSS underwent kidney biopsy (KB) over a period of 27 years. The median duration from pSS diagnosis to KB was 13.9 months. Seven patients (54%) had glomerulonephritis and 6 patients (46%) had tubulointerstitial nephritis. All patients were treated with corticosteroids and/or immunosuppressants. Eight patients (62%) remained stable or their renal function improved after a median follow-up of 12 months. CONCLUSIONS This case series reflects the broad spectrum of renal involvement in pSS. We observed that in our Hispanic population, glomerular involvement was the most frequent abnormality, mainly membranous glomerulopathy, followed by tubulointerstitial disease. Tubular atrophy and interstitial fibrosis were also common biopsy findings. Treatment with corticosteroids or other immunosuppressive agents appear to slow renal disease progression.
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Carrillo-Pérez DL, Tejeda-Maldonado J, Garza-García C, Soto-Abraham V, Hernández-Molina G, Molina-Paredes GA, Uribe-Uribe NO, Morales-Buenrostro LE. Biopsy-proven renal involvement and prognosis in 13 hispanic patients with primary Sjögren syndrome. ACTA ACUST UNITED AC 2018. [DOI: 10.1016/j.medcle.2017.11.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Yang HX, Wang J, Wen YB, Fei YY, Jiang MD, Zhou MY, Zhang W, Li H, Li XM, Zhang FC, Li XW, Zhang X, Chen LM. Renal involvement in primary Sjögren's syndrome: A retrospective study of 103 biopsy-proven cases from a single center in China. Int J Rheum Dis 2017; 21:223-229. [PMID: 28941123 DOI: 10.1111/1756-185x.13182] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM To retrospectively investigate the features of renal involvements in patients with primary Sjögren's syndrome (pSS) with biopsy results. METHODS A total of 2096 pSS inpatients at Peking Union Medical College Hospital in China from 2005 to 2015 were identified. Patients with biopsy-proven renal involvement (SS-renal) and matched controls (SS-only) were recruited. The clinical and pathologic features as well as treatments and outcomes were systematically analyzed. RESULTS One hundred and three pSS nephritis (inpatients had biopsy-proven renal involvement. Tubulointerstitial 53, 51.5%) was the prominent pathologic pattern with glomerulonephritis (GN) present in 50 (48.5%) of the renal lesions. The patterns of GN lesions included membranous nephropathy (37, 35.9%), mesangial proliferative glomerulonephritis (six, 5.8%) or immunoglobulin A nephropathy (three, 2.9%), minimal change disease (four, 3.9%) and focal segmental glomerulosclerosis (three, 2.9%). Compared to SS-only patients, SS-renal patients had fewer dry eyes and positive objective xerostomia (P < 0.05). They presented with a significantly lower incidence of interstitial lung disease (ILD), leukocytopenia and elevated immunoglobulin G levels (P < 0.05). They received a larger initial dosage of corticosteroid and had a higher mortality rate (P < 0.05). CONCLUSION This Chinese SS-renal population with biopsy results has diverse pathologic patterns and distinct clinical features. They are characterized with prominent renal-associated and mild SS-associated features. They received more vigorous treatment but had poorer prognosis.
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Affiliation(s)
- Hua-Xia Yang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College and The Ministry of Education Key Laboratory, Beijing, China
| | - Jing Wang
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu-Bing Wen
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yun-Yun Fei
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College and The Ministry of Education Key Laboratory, Beijing, China
| | - Meng-Di Jiang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College and The Ministry of Education Key Laboratory, Beijing, China
| | - Meng-Yu Zhou
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Zhang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College and The Ministry of Education Key Laboratory, Beijing, China
| | - Hang Li
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xue-Mei Li
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng-Chun Zhang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College and The Ministry of Education Key Laboratory, Beijing, China
| | - Xue-Wang Li
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuan Zhang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College and The Ministry of Education Key Laboratory, Beijing, China
| | - Li-Meng Chen
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Antibodies against citrullinated alpha enolase peptides in primary Sjogren's syndrome. Clin Immunol 2017; 183:300-303. [PMID: 28919520 DOI: 10.1016/j.clim.2017.09.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 09/06/2017] [Accepted: 09/13/2017] [Indexed: 01/04/2023]
Abstract
Citrullinated alpha enolase (CEP-1) has been designated as a major antigenic target of antibodies against citrullinated proteins (ACPA) in patients with rheumatoid arthritis (RA). Our aim is to determine the prevalence of anti-CEP-1 in a cohort of ACPA positive (ACPA+) primary Sjogren's syndrome (pSS) patients. Anti-CEP1 titers were determined by ELISA in sera from 15 ACPA+ and 45 ACPA- age/sex matched pSS; 12 ACPA+ RA patients and 30 healthy controls (HC). Increased anti-CEP-1 antibody titers were detected in nine out of the 15 (60%) ACPA+ pSS patients and 5 out of 12 (41.7%) ACPA+ RA patients; no reactivities were detected in ACPA- pSS patients and HC. Anti-CEP-1 antibodies in the setting of pSS were associated with higher urine pH levels at baseline. CEP-1 is a major antigenic target of ACPA in patients with pSS characterizing a subgroup with distinct laboratory features.
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Chronic Autoimmune Epithelitis in Sjögren's Syndrome and Primary Biliary Cholangitis: A Comprehensive Review. Rheumatol Ther 2017; 4:263-279. [PMID: 28791611 PMCID: PMC5696286 DOI: 10.1007/s40744-017-0074-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Indexed: 12/12/2022] Open
Abstract
Within the spectrum of autoimmune diseases, Sjögren's syndrome and primary biliary cholangitis are exemplary and can be coined as chronic epithelitis based on their frequent coexistence in clinical practice and the highly specific immune-mediated injury of the small bile ducts and the exocrine glands. The pathogenic mechanisms underlying the diseases are similar, with apoptosis being the key element leading to organ-specific immune-mediated injury directed against the small bile ducts and salivary gland epithelia, respectively along with similar epidemiological features, such as female predominance and the age of onset in the fifth decade of life. Indeed, novel insights into the pathogenesis of the diseases have been obtained in recent years, including a better definition of the role of B and T cells, particularly Th17 cells, and the mechanisms of autoantibody-mediated tissue injury, with anti-mitochondrial antibodies and SS-A/SS-B being identified as specific for primary biliary cholangitis and Sjögren's syndrome, respectively. These findings have opened the possibility to new targeted therapies, but most clinical needs remain unmet, particularly from a therapeutic standpoint where options diverge, with bile acids being the predominant treatment strategy in primary biliary cholangitis and immunomodulators being used to treat Sjögren's syndrome. Here we provide a comprehensive review of the most recent findings on the pathogenesis, clinical manifestations and therapeutic options for Sjögren's syndrome and primary biliary cholangitis, respectively, while stressing the common traits between these conditions. Our cumulative hypothesis is that similarities outnumber differences and that this may prove advantageous towards a better management of patients.
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40
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Jasiek M, Karras A, Le Guern V, Krastinova E, Mesbah R, Faguer S, Jourde-Chiche N, Fauchais AL, Chiche L, Dernis E, Moulis G, Fraison JB, Lazaro E, Jullien P, Hachulla E, Le Quellec A, Rémy P, Hummel A, Costedoat-Chalumeau N, Ronco P, Vanhille P, Meas-Yedid V, Cordonnier C, Ferlicot S, Daniel L, Seror R, Mariette X, Thervet E, François H, Terrier B. A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren's syndrome. Rheumatology (Oxford) 2017; 56:362-370. [PMID: 27940588 DOI: 10.1093/rheumatology/kew376] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Indexed: 12/24/2022] Open
Abstract
Objective. Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment. Methods. We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American-European Consensus Group criteria or enlarged American-European Consensus Group criteria, and with biopsy-proven renal involvement. Results. A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of <60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m 2 at baseline, P < 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study. Conclusion. Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease.
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Affiliation(s)
- Magali Jasiek
- Department of Nephrology, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, Le Kremlin-Bicêtre
| | - Alexandre Karras
- Department of Nephrology, Hôpital Européen Georges Pompidou, AP-HP
| | - Véronique Le Guern
- Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris
| | - Evguenia Krastinova
- Department of Epidemiology and Statistics, Hôpital Bicêtre, AP-HP, Université Paris-Sud, Le Kremlin-Bicêtre
| | - Rafik Mesbah
- Department of Nephrology, Centre Hospitalier, Boulogne-Sur-Mer
| | - Stanislas Faguer
- Department of Nephrology and Organ Transplantation, Hôpital Rangueil, Toulouse
| | | | | | - Laurent Chiche
- Department of Internal Medicine, Hôpital Européen, Marseille
| | | | | | | | | | - Perrine Jullien
- Department of Internal Medicine, CHU Saint-Étienne, Saint-Étienne
| | - Eric Hachulla
- Department of Internal Medicine, Hôpital Claude Huriez, Université Lille 2, Lille
| | - Alain Le Quellec
- Department of Internal Medicine, Hôpital Saint-Eloi, Montpellier
| | - Philippe Rémy
- Department of Nephrology, Hôpital Henri Mondor, Créteil
| | | | - Nathalie Costedoat-Chalumeau
- Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris
| | | | | | | | | | - Sophie Ferlicot
- Department of Pathology, Hôpital Bicêtre, AP-HP, Université Paris-Sud, Le Kremlin-Bicêtre
| | | | - Raphaele Seror
- Department of Rheumatology, Hôpital Bicêtre, AP-HP, Université Paris-Sud, Le Kremlin-Bicêtre.,Center of Immunology of Viral and Autoimmune Diseases (IMVA), INSRM U1184, Le Kremlin-Bicêtre, France
| | - Xavier Mariette
- Department of Rheumatology, Hôpital Bicêtre, AP-HP, Université Paris-Sud, Le Kremlin-Bicêtre.,Center of Immunology of Viral and Autoimmune Diseases (IMVA), INSRM U1184, Le Kremlin-Bicêtre, France
| | - Eric Thervet
- Department of Nephrology, Hôpital Européen Georges Pompidou, AP-HP
| | - Hélène François
- Department of Nephrology, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, Le Kremlin-Bicêtre
| | - Benjamin Terrier
- Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris
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Affiliation(s)
- Seon-Ho Ahn
- Division of Nephrology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Iksan, Korea
| | - Jong Hwan Jung
- Division of Nephrology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Iksan, Korea
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Liu C, Zhang H, Yao G, Hu Y, Qi J, Wang Y, Chen W, Tang X, Li W, Lu L, Gu L, Sun L. Characteristics of primary Sjögren’s syndrome patients with IgG4 positive plasma cells infiltration in the labial salivary glands. Clin Rheumatol 2016; 36:83-88. [DOI: 10.1007/s10067-016-3472-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 09/14/2016] [Accepted: 10/27/2016] [Indexed: 12/24/2022]
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Primary Sjögren’s syndrome: clinical phenotypes, outcome and the development of biomarkers. Immunol Res 2016; 65:331-344. [DOI: 10.1007/s12026-016-8844-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Goules AV, Tzioufas AG. Primary Sjӧgren's syndrome: Clinical phenotypes, outcome and the development of biomarkers. Autoimmun Rev 2016; 15:695-703. [DOI: 10.1016/j.autrev.2016.03.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Accepted: 02/29/2016] [Indexed: 11/25/2022]
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45
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Lionaki S, Gakiopoulou H, Boletis JN. Understanding the complement-mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies. APMIS 2016; 124:725-35. [PMID: 27356907 DOI: 10.1111/apm.12566] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 05/13/2016] [Indexed: 01/16/2023]
Abstract
An enhanced understanding of the role of complement in the pathogenesis of membranoproliferative glomerulonephritis has led to reclassification of the latter into immunoglobulin-mediated and non-immunoglobulin-mediated disease. The new classification schema resulted in improved diagnostic clinical algorithms, while it brought into light again the diseases, which are characterized by the presence of glomerular deposits, composed predominantly by C3, in the absence of significant amounts of immunoglobulins in renal biopsy, namely, C3 glomerulopathies (dense deposit disease and C3 glomerulonephritis). Despite the lack of randomized controlled trials following the advances in the understanding of the pathogenetic pathways involved in membranoproliferative glomerulonephritis, it is important that the new mechanistic approach has opened new roads for the exploration and discovery of targeted therapies.
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Affiliation(s)
- Sophia Lionaki
- Nephrology Department, Laiko Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Hara Gakiopoulou
- Department of Pathology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - John N Boletis
- Nephrology Department, Laiko Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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Abstract
Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by lymphoplasmacytic infiltration of the exocrine (salivary and lachrymal) glands that results in sicca symptoms (dryness of the eyes and mouth). Systemic complications can occur in pSS, but renal involvement is rare, affecting <10% patients. The most frequent form of nephropathy in pSS is tubulointerstitial nephritis (TIN), in which infiltration of the kidney by plasma cells is a key feature and shows similarity to the lymphoplasmacytic infiltration of the salivary glands. Electrolyte disturbances may occur in pSS, such as renal distal tubular acidosis, diabetes insipidus, Gitelman syndrome or Fanconi syndrome. Glomerular involvement is less frequently detected in patients with pSS, but usually takes the form of membranoproliferative glomerulonephritis secondary to cryoglobulinaemia. The renal prognosis in patients with pSS and TIN or glomerular disease is usually favourable, but the risk of chronic kidney disease remains high in patients with TIN. Appropriate screening must be performed at least once a year in patients with systemic pSS in order to facilitate the early detection of renal complications. In this Review we discuss the epidemiology, pathophysiology, differential diagnosis and treatment of renal disease in pSS.
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Affiliation(s)
- Hélène François
- Department of Nephrology, Dialysis, and Transplantation, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Saclay, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, Paris, France
| | - Xavier Mariette
- Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Saclay, IMVA Centre of Immunology of Viral Infections and Autoimmune Diseases, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, Paris, France
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Abstract
We present a middle-aged woman with a prior history of central nervous system (CNS) demyelinating disorder who presented with an acute onset quadriparesis and respiratory failure. The evaluation revealed distal renal tubular acidosis with hypokalemia and medullary nephrocalcinosis. Weakness persisted despite potassium correction, and ongoing evaluation confirmed recurrent CNS and long-segment spinal cord demyelination with anti-aquaporin-4 antibodies. There was no history of dry eyes or dry mouth. Anti-Sjogren's syndrome A antigen antibodies were elevated, and there was reduced salivary flow on scintigraphy. Coexistent antiphospholipid antibody syndrome with inferior vena cava thrombosis was also found on evaluation. The index patient highlights several rare manifestations of primary Sjogren's syndrome (pSS) as the presenting features and highlights the differential diagnosis of the clinical syndromes in which pSS should be considered in the Intensive Care Unit.
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Affiliation(s)
- Srinivas Rajagopala
- Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Puducherry, India
| | - Gurukiran Danigeti
- Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Puducherry, India
| | - Dharanipragada Subrahmanyan
- Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Puducherry, India
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Kuo CF, Grainge MJ, Valdes AM, See LC, Luo SF, Yu KH, Zhang W, Doherty M. Familial Risk of Sjögren's Syndrome and Co-aggregation of Autoimmune Diseases in Affected Families: A Nationwide Population Study. Arthritis Rheumatol 2015; 67:1904-12. [PMID: 25940005 PMCID: PMC5034806 DOI: 10.1002/art.39127] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 03/19/2015] [Indexed: 01/02/2023]
Abstract
Objective To investigate familial aggregation of Sjögren's syndrome (SS) and the relative risks (RRs) of other autoimmune disease in relatives of patients with SS. Methods We identified 23,658,577 beneficiaries enrolled in the Taiwan National Health Insurance system in 2010, of whom 12,754 had SS. We identified 21,009,551 parent–child relationships and 17,168,340 pairs of full siblings. The familial risks of SS and other autoimmune diseases, tetrachoric correlation, and familial transmission were estimated. Results We identified 105 patients with SS who had an affected first‐degree relative. The RR of SS was 18.99 (95% confidence interval [95% CI] 9.76–36.93) in siblings of patients with SS, 11.31 (95% CI 8.34–15.33) in offspring, and 12.46 (95% CI 9.34–16.62) in parents. Tetrachoric correlation coefficients were 0.53 (95% CI 0.41–0.65) for cotwins of affected individuals and 0.21 (95% CI 0.16–0.26) for full siblings. The familial transmission (heritability plus shared environmental contribution) was 0.54 (95% CI 0.44–0.77). In first‐degree relatives of patients with SS, the RRs were 2.95 (95% CI 2.33–3.73) for rheumatoid arthritis, 6.25 (95% CI 5.15–7.58) for systemic lupus erythematosus, 2.39 (95% CI 0.77–7.41) for systemic sclerosis, 0.71 (95% CI 0.10–5.07) for idiopathic inflammatory myopathy, 1.97 (95% CI 1.29–3.02) for type 1 diabetes mellitus, 3.38 (95% CI 1.26–9.05) for multiple sclerosis, 1.67 (95% CI 0.83–3.33) for myasthenia gravis, 1.25 (95% CI 1.04–1.50) for psoriasis, 1.21 (95% CI 0.39–3.76) for inflammatory bowel disease, and 2.29 (95% CI 1.19–4.40) for vasculitis. Conclusion The risk of SS and other autoimmune diseases is increased in relatives of patients with SS, and more than one‐half of phenotypic variance in SS can be explained by familial factors.
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Affiliation(s)
- Chang-Fu Kuo
- University of Nottingham, Nottingham, UK, and Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | | | | | | | - Shue-Fen Luo
- Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Kuang-Hui Yu
- Chang Gung Memorial Hospital, Taoyuan City, Taiwan
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Gravani F, Papadaki I, Antypa E, Nezos A, Masselou K, Ioakeimidis D, Koutsilieris M, Moutsopoulos HM, Mavragani CP. Subclinical atherosclerosis and impaired bone health in patients with primary Sjogren's syndrome: prevalence, clinical and laboratory associations. Arthritis Res Ther 2015; 17:99. [PMID: 25886059 PMCID: PMC4416325 DOI: 10.1186/s13075-015-0613-6] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 03/30/2015] [Indexed: 12/17/2022] Open
Abstract
Introduction To determine the prevalence and clinical/laboratory associations of subclinical atherosclerosis and impaired bone health in primary Sjogren’s syndrome (SS). Methods 64 consecutive patients with primary SS, 77 with rheumatoid arthritis (RA) and 60 healthy controls (HC) οf similar age and sex distribution were enrolled. Demographics, clinical/laboratory features, classical risk factors for atherosclerosis and osteoporosis (OP) were recorded. Intima-medial thickness scores (IMT) and carotid/femoral (C/F) plaque formation, as well as bone mineral density (BMD) and fractures were evaluated. Determinants of IMT/BMD levels and the presence of plaque were assessed by univariate and multivariate models. Serum levels of the Wnt signaling mediators Dickkopf-related protein 1(DKK1) and sclerostin were determined in primary SS patients and HC. Results Increased arterial wall thickening (IMT > 0.90 mm) and impaired bone health (defined as OP or osteopenia), were detected in approximately two-thirds of primary SS and RA patients, with a mean IMT value being significantly increased compared to HC. The presence of primary SS emerged as an independent risk factor for arterial wall thickening when traditional risk factors for cardiovascular disease (CVD) including age, sex, hypertension, smoking (pack/years), LDL and HDL levels were taken into account in a multivariate model [adjusted OR 95% (CI): 2.8 (1.04-7.54)]. In primary SS, age was revealed as independent predictor of increased IMT scores; age and lymphopenia as well as increased urine pH as independent determinants of C/F plaque formation and OP/osteopenia, respectively. An independent association of OP/osteopenia with plaque formation was observed when independent predictors for both variables were considered, with low DKK1 levels being associated with both plaque formation and lower BMD levels. Conclusions Comorbidities such as subclinical atherosclerosis and impaired bone health occur frequently in primary SS, in association with disease related features and traditional risk factors. Wnt signaling mediators are potentially involved in the pathogenesis of both entities. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0613-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Fotini Gravani
- Department of Rheumatology, General Hospital of Athens "G.Gennimatas", Athens, Greece. .,Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece.
| | - Ioanna Papadaki
- Department of Rheumatology, General Hospital of Athens "G.Gennimatas", Athens, Greece.
| | - Eleni Antypa
- Department of Radiology, General Hospital of Athens "G.Gennimatas", Athens, Greece.
| | - Andrianos Nezos
- Department of Physiology, School of Medicine, University of Athens, M. Asias 75, Athens, 11527, Greece.
| | - Kyriaki Masselou
- Department of Immunology, General Hospital of Athens "G. Gennimatas", Athens, Greece.
| | - Dimitrios Ioakeimidis
- Department of Rheumatology, General Hospital of Athens "G.Gennimatas", Athens, Greece.
| | - Michael Koutsilieris
- Department of Physiology, School of Medicine, University of Athens, M. Asias 75, Athens, 11527, Greece.
| | | | - Clio P Mavragani
- Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece. .,Department of Physiology, School of Medicine, University of Athens, M. Asias 75, Athens, 11527, Greece.
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Kidder D, Rutherford E, Kipgen D, Fleming S, Geddes C, Stewart GA. Kidney biopsy findings in primary Sjögren syndrome. Nephrol Dial Transplant 2015; 30:1363-9. [PMID: 25817222 DOI: 10.1093/ndt/gfv042] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2014] [Accepted: 02/02/2015] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Renal involvement is rare in primary Sjögren syndrome (PSS). In this study, we examined renal biopsy findings in patients with PSS and correlated them with their clinical and renal findings. METHODS Twenty-five patients with PSS who underwent renal biopsies from two renal units in Scotland between 1978 and 2013 were identified from renal biopsy database. We examined the renal morphologic, clinical and renal findings at the time of renal biopsy, renal and patient outcomes. RESULTS The diagnosis of PSS preceded renal biopsy in 18/25 patients. In this group, the median duration of the disease was 5.5 years. Significant proteinuria, combined microscopic haematuria and proteinuria and reduced renal excretory function were found in 76, 56 and 84% of patients, respectively. The 3-year actuarial patient survival was significantly lower in patients with glomerulonephritis as compared with tubulointerstitial nephritis (66 versus 100%, P = 0.02). There was no difference in 3-year actuarial renal survival between these two groups (92 versus 92%, P = 1.0). CONCLUSIONS Renal biopsy is rare in PSS and often reveals diverse pathological findings. Glomerulonephritis, as compared with tubulointerstitial nephritis, is associated with higher early mortality. Further studies are needed to evaluate the utility of renal biopsy and its impact on disease management.
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Affiliation(s)
- Dana Kidder
- Renal Unit, Aberdeen Royal Infirmary, Aberdeen, UK
| | | | - David Kipgen
- Pathology Department, Southern General Hospital, Glasgow, UK
| | - Stewart Fleming
- Department of Pathology, Ninewells Medical School, Dundee, UK
| | - Colin Geddes
- Glasgow Renal and Transplant Unit, Western Infirmary, Glasgow, UK
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