Skip to main content

Advertisement

SpringerLink
Log in

Renal tubular acidosis and associated factors in patients with primary Sjögren’s syndrome: a registry-based study

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objectives

To investigate the clinical features and factors associated with primary Sjögren’s syndrome (pSS)–associated renal tubular acidosis (RTA).

Method

This case–control study was based on a multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients with pSS, including those with RTA and those without renal involvement, between May 2016 and March 2020 were included in the analysis. Demographic, clinical, and laboratory data were also collected. Univariate and multivariate logistic regression analyses were used to identify factors that were associated with pSS-RTA.

Results

This study included 257 pSS patients with RTA and 4222 patients without renal involvement. Significantly younger age at disease onset (40.1 ± 14.1 vs. 46.2 ± 13.1 years, P < 0.001), longer diagnosis interval (15.0 interquartile range [IQR] [1.0, 48.0] vs. 6.0 IQR [0, 34.0] months, P < 0.001), higher EULAR Sjögren’s syndrome disease activity index (9 IQR [5, 15] vs. 3 IQR [0, 8], P < 0.001), and a higher prevalence of decreased estimated glomerular filtration rate (25.0% vs. 6.6%, P < 0.001) were observed in pSS patients with RTA than in those without renal involvement. Factors that were independently associated with pSS-RTA included age at disease onset ≤ 35 years (odds ratio [OR] 3.00, 95% confidence interval [CI] 2.27–3.97), thyroid disorders (OR 1.49, 95% CI 1.04–2.14), subjective dry mouth (OR 3.29, 95% CI 1.71–6.35), arthritis (OR 1.57, 95% CI 1.10–2.25), anti-SSB antibody positivity (OR 1.80, 95% CI 1.33–2.45), anemia (OR 1.67, 95% CI 1.26–2.21), elevated alkaline phosphatase level (OR 2.14, 95% CI 1.26–3.65), decreased albumin level (OR 1.61, 95% CI 1.00–2.60), and elevated erythrocyte sedimentation rate (OR 1.78, 95% CI 1.16–2.73).

Conclusions

Delayed diagnosis and decreased kidney function are common in pSS patients with RTA. pSS should be considered in patients with RTA, and early recognition and treatment may be useful in slowing the deterioration of renal function in patients with pSS-RTA.

Key Points

• pSS patients with RTA have earlier disease onset and higher disease activity than pSS patients without RTA, but the diagnosis was frequently delayed.

• Decreased kidney function are common in pSS patients with RTA.

• Sjögren’s syndrome should be considered in young female patients with unexplained RTA, whereas RTA should be screened in pSS patients with early disease onset and elevated ALP level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. McCoy SS, Bartels CM, Saldanha IJ et al (2021) National Sjogren’s Foundation Survey: burden of oral and systemic involvement on quality of life. J Rheumatol 48:1029–1036. https://doi.org/10.3899/jrheum.200733

    Article  Google Scholar 

  2. Singh AG, Singh S, Matteson EL (2016) Rate, risk factors and causes of mortality in patients with Sjogren’s syndrome: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 55:450–460. https://doi.org/10.1093/rheumatology/kev354

    Article  Google Scholar 

  3. Evans R, Zdebik A, Ciurtin C, Walsh SB (2015) Renal involvement in primary Sjogren’s syndrome. Rheumatology (Oxford) 54:1541–1548. https://doi.org/10.1093/rheumatology/kev223

    Article  CAS  Google Scholar 

  4. Ohtani H, Imai H, Kodama T et al (1999) Severe hypokalaemia and respiratory arrest due to renal tubular acidosis in a patient with Sjogren syndrome. Nephrol Dial Transplant 14:2201–2203. https://doi.org/10.1093/ndt/14.9.2201

    Article  CAS  Google Scholar 

  5. Ren H, Wang WM, Chen XN et al (2008) Renal involvement and followup of 130 patients with primary Sjogren’s syndrome. J Rheumatol 35:278–284

    CAS  Google Scholar 

  6. Aasarod K, Haga HJ, Berg KJ, Hammerstrom J, Jorstad S (2000) Renal involvement in primary Sjogren’s syndrome. QJM 93:297–304. https://doi.org/10.1093/qjmed/93.5.297

    Article  CAS  Google Scholar 

  7. Jain A, Srinivas BH, Emmanuel D, Jain VK, Parameshwaran S, Negi VS (2018) Renal involvement in primary Sjogren’s syndrome: a prospective cohort study. Rheumatol Int 38:2251–2262. https://doi.org/10.1007/s00296-018-4118-x

    Article  Google Scholar 

  8. Pertovaara M, Korpela M, Kouri T, Pasternack A (1999) The occurrence of renal involvement in primary Sjogren’s syndrome: a study of 78 patients. Rheumatology (Oxford) 38:1113–1120. https://doi.org/10.1093/rheumatology/38.11.1113

    Article  CAS  Google Scholar 

  9. Both T, Hoorn EJ, Zietse R et al (2015) Prevalence of distal renal tubular acidosis in primary Sjogren’s syndrome. Rheumatology (Oxford) 54:933–939. https://doi.org/10.1093/rheumatology/keu401

    Article  CAS  Google Scholar 

  10. Li M, Tian X, Zhang W, Leng X, Zeng X (2015) CRDC: a Chinese rheumatology research platform. Clin Rheumatol 34:1347–1352. https://doi.org/10.1007/s10067-015-3003-1

    Article  Google Scholar 

  11. Xu D, Zhao S, Li Q et al (2020) Characteristics of Chinese patients with primary Sjogren’s syndrome: preliminary report of a multi-centre registration study. Lupus 29:45–51. https://doi.org/10.1177/0961203319889666

    Article  CAS  Google Scholar 

  12. Vitali C, Bombardieri S, Jonsson R et al (2002) Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61:554–558. https://doi.org/10.1136/ard.61.6.554

    Article  CAS  Google Scholar 

  13. Shiboski CH, Shiboski SC, Seror R et al (2017) 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 76:9–16. https://doi.org/10.1136/annrheumdis-2016-210571

    Article  Google Scholar 

  14. Trepiccione F, Walsh SB, Ariceta G et al (2021) Distal renal tubular acidosis: ERKNet/ESPN clinical practice points. Nephrol Dial Transplant 36:1585–1596. https://doi.org/10.1093/ndt/gfab171

    Article  CAS  Google Scholar 

  15. Goules A, Geetha D, Arend LJ, Baer AN (2019) Renal involvement in primary Sjogren’s syndrome: natural history and treatment outcome. Clin Exp Rheumatol 37(Suppl 118):123–132

    Google Scholar 

  16. Zhang Y, Li M, Zhang L et al (2020) Association between comorbidities and extraglandular manifestations in primary Sjogren’s syndrome: a multicenter cross-sectional study. Clin Rheumatol 39:2677–2688. https://doi.org/10.1007/s10067-020-04992-x

    Article  Google Scholar 

  17. Seror R, Ravaud P, Bowman SJ et al (2010) EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis 69:1103–1109. https://doi.org/10.1136/ard.2009.110619

    Article  Google Scholar 

  18. Seror R, Ravaud P, Mariette X et al (2011) EULAR Sjogren’s syndrome patient reported index (ESSPRI): development of a consensus patient index for primary Sjogren’s syndrome. Ann Rheum Dis 70:968–972. https://doi.org/10.1136/ard.2010.143743

    Article  Google Scholar 

  19. Vitali C, Palombi G, Baldini C et al (2007) Sjogren’s syndrome disease damage index and disease activity index: scoring systems for the assessment of disease damage and disease activity in Sjogren’s syndrome, derived from an analysis of a cohort of Italian patients. Arthritis Rheum 56:2223–2231. https://doi.org/10.1002/art.22658

    Article  Google Scholar 

  20. Malladi AS, Sack KE, Shiboski SC et al (2012) Primary Sjogren’s syndrome as a systemic disease: a study of participants enrolled in an international Sjogren’s syndrome registry. Arthritis Care Res (Hoboken) 64:911–918. https://doi.org/10.1002/acr.21610

    Article  Google Scholar 

  21. Viergever PP, Swaak TJG (1991) Renal tubular dysfunction in primary sjogrens-syndrome - clinical-studies in 27 patients. Clin Rheumatol 10:23–27. https://doi.org/10.1007/bf02208028

    Article  CAS  Google Scholar 

  22. Wei L, Zhifei X, Xiaoran N et al (2022) Patients with early-onset primary Sjogren’s syndrome have distinctive clinical manifestations and circulating lymphocyte profiles. Rheumatology (Oxford) 61:597–605. https://doi.org/10.1093/rheumatology/keab367

    Article  CAS  Google Scholar 

  23. Brito-Zeron P, Acar-Denizli N, Ng WF et al (2018) How immunological profile drives clinical phenotype of primary Sjogren’s syndrome at diagnosis: analysis of 10,500 patients (Sjogren Big Data Project). Clin Exp Rheumatol 36(Suppl 112):102–112

    Google Scholar 

  24. Cafaro G, Perricone C, Baldini C et al (2020) Significance of anti-La/SSB antibodies in primary Sjogren’s syndrome patients with combined positivity for anti-Ro/SSA and salivary gland biopsy. Clin Exp Rheumatol 38(Suppl 126):53–56

    Google Scholar 

  25. Luo J, Huo YW, Wang JW, Guo H (2019) High-risk indicators of renal involvement in primary Sjogren’s syndrome: a clinical study of 1002 cases. J Immunol Res 2019:3952392. https://doi.org/10.1155/2019/3952392

    Article  CAS  Google Scholar 

  26. Narvaez J, Sanchez-Piedra C, Fernandez-Castro M et al (2020) Clinically significant renal involvement in primary Sjogren’s syndrome is associated with important morbidity: data from the Spanish Sjogrenser cohort. Clin Exp Rheumatol 38(Suppl 126):116–124

    Google Scholar 

  27. Jasiek M, Karras A, Le Guern V et al (2017) A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjogren’s syndrome. Rheumatology (Oxford) 56:362–370. https://doi.org/10.1093/rheumatology/kew376

    Article  CAS  Google Scholar 

  28. Takemoto F, Hoshino J, Sawa N et al (2005) Autoantibodies against carbonic anhydrase II are increased in renal tubular acidosis associated with Sjogren syndrome. Am J Med 118:181–184. https://doi.org/10.1016/j.amjmed.2004.07.049

    Article  CAS  Google Scholar 

  29. Koh JH, Park Y, Lee J, Park SH, Kwok SK (2021) Hypergammaglobulinaemia predicts glandular and extra-glandular damage in primary Sjogren’s syndrome: results from the KISS cohort study. Clin Exp Rheumatol 39 Suppl 133:114–122. https://doi.org/10.55563/clinexprheumatol/volsh1

    Article  Google Scholar 

  30. Hong R, Xu D, Hsieh E et al (2020) Factors associated with renal involvement in primary Sjogren’s syndrome: a meta-analysis. Front Med (Lausanne) 7:614482. https://doi.org/10.3389/fmed.2020.614482

    Article  Google Scholar 

  31. Francois H, Mariette X (2016) Renal involvement in primary Sjogren syndrome. Nat Rev Nephrol 12:82–93. https://doi.org/10.1038/nrneph.2015.174

    Article  CAS  Google Scholar 

  32. Ramos-Casals M, Brito-Zeron P, Solans R et al (2014) Systemic involvement in primary Sjogren’s syndrome evaluated by the EULAR-SS disease activity index: analysis of 921 Spanish patients (GEAS-SS Registry). Rheumatology (Oxford) 53:321–331. https://doi.org/10.1093/rheumatology/ket349

    Article  Google Scholar 

  33. Siamopoulos KC, Elisaf M, Drosos AA, Mavridis AA, Moutsopoulos HM (1992) Renal tubular acidosis in primary Sjogren’s syndrome. Clin Rheumatol 11:226–230. https://doi.org/10.1007/BF02207962

    Article  CAS  Google Scholar 

  34. Fauchais AL, Ouattara B, Gondran G et al (2010) Articular manifestations in primary Sjogren’s syndrome: clinical significance and prognosis of 188 patients. Rheumatology (Oxford) 49:1164–1172. https://doi.org/10.1093/rheumatology/keq047

    Article  Google Scholar 

  35. Mason AM, Golding PL (1970) Renal tubular acidosis and autoimmune thyroid disease. Lancet 2:1104–1107. https://doi.org/10.1016/s0140-6736(70)92296-8

    Article  CAS  Google Scholar 

  36. Sandhya P, Danda D, Rajaratnam S, Thomas N (2014) Sjogren’s, renal tubular acidosis and osteomalacia - an Asian Indian series. Open Rheumatol J 8:103–109. https://doi.org/10.2174/1874312901408010103

    Article  Google Scholar 

  37. Domrongkitchaiporn S, Pongsakul C, Stitchantrakul W et al (2001) Bone mineral density and histology in distal renal tubular acidosis. Kidney Int 59:1086–1093. https://doi.org/10.1046/j.1523-1755.2001.0590031086.x

    Article  CAS  Google Scholar 

  38. Both T, Zillikens MC, Hoorn EJ et al (2016) Bone mineral density in Sjögren syndrome patients with and without distal renal tubular acidosis. Calcif Tissue Int 98:573–579. https://doi.org/10.1007/s00223-016-0112-z

    Article  CAS  Google Scholar 

  39. Goules AV, Tatouli IP, Moutsopoulos HM, Tzioufas AG (2013) Clinically significant renal involvement in primary Sjogren’s syndrome: clinical presentation and outcome. Arthritis Rheum 65:2945–2953. https://doi.org/10.1002/art.38100

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledged the contributions from all medical centers in the CRDC all over China and the HealthCloud Co., Ltd, as the system provider.

Funding

This study was supported by the Chinese National Key Technology R&D Program, Ministry of Science and Technology (2017YFC0907601, 2017YFC0907605), and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-005).

Author information

Author notes

  1. Yuying Zhang, Lin Qiao, and Liyun Zhang contributed equally to this study.

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China

    Yuying Zhang, Lin Qiao, Jiuliang Zhao, Dong Xu, Mengtao Li, Yan Zhao & Xiaofeng Zeng

  2. Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Yuying Zhang

  3. Department of Rheumatology, Shanxi Bethune Hospital, Taiyuan, China

    Liyun Zhang

  4. Department of Rheumatology, The First People’s Hospital of Yunnan Province, Kunming, China

    Qin Li

  5. Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang, China

    Pinting Yang

  6. Department of Rheumatology and Immunology, The Second Hospital of Dalian Medical University, Dalian, China

    Xiaodan Kong

  7. Department of Rheumatology, The Second Affiliated Hospital of Nanchang University, Nanchang, China

    Xinwang Duan

  8. Department of Rheumatology, Jiangsu Provincial People’s Hospital, Nanjing, China

    Miaojia Zhang

  9. Department of Rheumatology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei, China

    Xiaomei Li

  10. Department of Rheumatology, The First Affiliated Hospital of Baotou Medical College, Baotou, China

    Yongfu Wang

  11. Department of Rheumatology, First Affiliated Hospital of Kunming Medical University, Kunming, China

    Jian Xu

  12. Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China

    Yanhong Wang

  13. Section of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Yale School of Medicine, New Haven, USA

    Evelyn Hsieh

Authors
  1. Yuying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liyun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pinting Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaodan Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xinwang Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Miaojia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaomei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yongfu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jian Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yanhong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Evelyn Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jiuliang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Dong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mengtao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Yan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Xiaofeng Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MTL, LYZ, JLZ, DX, YZ, and XFZ contributed to the conception and design of the study. LQ, LYZ, QL, JL, PTY, XDK, XWD, MJZ, XML, YFW, and JX contributed to data collection. YYZ and YHW participated in statistical analysis and interpretation. YYZ drafted the manuscript. MTL and DX revised the manuscript critically. DX, MTL, YZ, and XFZ supervised the study. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Dong Xu or Mengtao Li.

Ethics declarations

Ethics approval and consent to participate

Written informed consent was obtained from all patients at enrollment. Ethics approval for the registry was obtained from the Medical Ethics Committee of Peking Union Medical College Hospital (JS-2038).

Disclosures

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 29 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Qiao, L., Zhang, L. et al. Renal tubular acidosis and associated factors in patients with primary Sjögren’s syndrome: a registry-based study. Clin Rheumatol 42, 431–441 (2023). https://doi.org/10.1007/s10067-022-06426-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-022-06426-2

Keywords

Search

Navigation