Renal involvement in primary Sjogren’s syndrome: a prospective cohort study
The objective of the study is to prospectively evaluate the spectrum of clinical and subclinical renal involvement in patients with primary Sjogren’s syndrome (pSS). Of the 174 patients screened, seventy patients with pSS underwent renal function tests, urine examination, renal ultrasound, arterial blood gases, urine pH followed by urine acidification test and renal biopsy (if indicated). Renal tubular acidosis (RTA) was treated with alkali replacement and moderate–severe tubulointerstitial nephritis (TIN) was treated with oral prednisolone. Sixty-two patients completed 1-year follow-up. A comparison was made between patients with and without renal involvement. Thirty-five (50%) patients had renal involvement. They had a lower baseline eGFR (71.85 ± 18.04 vs. 83.8 ± 17, p = 0.005). Twenty-nine patients had RTA (25 complete and 4 incomplete). Eleven patients had urinary abnormalities. Patients with RTA (n = 29) were younger (34.9 ± 9 vs. 42 ± 11.3, p = 0.006), had fewer articular (34% vs. 78%, p = 0.001) and ocular sicca (62% vs. 88%, P = 0.01) than those without RTA (n = 41) and commonly presented with hypokalemic paralysis. On biopsy, TIN (9/17) and IgA nephropathy (3/17) were most common. On follow-up, there was no clinically significant change in eGFR; however, one patient with renal calculi and incomplete distal renal tubular acidosis (dRTA) progressed to complete dRTA. Two patients treated with steroids had marginal improvement in eGFR. Renal involvement in pSS is under-recognized with the most common manifestation being RTA presenting with hypokalemic paralysis. These patients are younger with less articular and sicca symptoms. Subclinical RTA may progress to complete RTA. Renal biopsy should be considered in all patients with renal involvement.
KeywordsPrimary Sjogren’s syndrome Tubulointerstitial nephritis Sicca Renal tubular acidosis Renal biopsy Hypokalemic paralysis
Primary Sjogren’s syndrome
Renal tubular acidosis
Estimated glomerular filtration rate
Distal renal tubular acidosis
Incomplete distal renal tubular acidosis
American–European consensus group
Enzyme-linked immunosorbent assay
Arterial blood gases
Urine acidification test
Complete distal renal tubular acidosis
EULAR Sjögren’s Syndrome Disease Activity Index
Non-steroidal anti-inflammatory drugs
Moderate interstitial fibrosis and tubular atrophy
Focal segmental glomerulosclerosis
Acute tubular necrosis
Chronic interstitial nephritis
Statistical package for the social sciences
Sjogren’s syndrome-related antigen A
Sjogren’s syndrome-related antigen B
The authors thank Dr. Gunjan Kumar, Senior resident PSM, for statistical analysis.
(1) The conception and design of the study—AJ, SBH, SP, and VSN. Acquisition of data—AJ, SBH, DE, and VKJ. Analysis and interpretation of data—AJ, SBH, DE, and VKJ. (2) Drafting the article—AJ, DE, and VKJ. Revising it critically for important intellectual content—SBH, SP, and VSN. (3) Final approval of the version to be submitted—AJ, SBH, DE, VKJ, SP, and VSN. (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved—AJ, SBH, DE, VKJ, SP, and VSN.
This study was funded by Intramural Research fund, Jawaharlal Institute of Postgraduate Medicine and Research (Grant number: JIP/Res/Intra-DM, M.Ch/01/2015-16 and JIP/Res/Intra-DM, M.Ch/phas1/grant2/01/2016-17).
Compliance with ethical standards
Conflict of interest
None of the authors have any conflict of interest to declare.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approved by the Institute Ethics Committee of Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India, held on 11th December, 2014 (JIP/IEC/2014/8/441).
Informed consent was obtained from all individual participants included in the study.
- 3.Lin DF (2010) Clinical and prognostic characteristics of 573 cases of primary Sjogren’s syndrome. Chin Med J (Engl) 123:3252–3257Google Scholar
- 10.Jasiek M, Karras A, Le Guern V, Krastinova E, Mesbah R, Faguer S, Jourde-Chiche N, Fauchais A-L, Chiche L, Dernis E, Moulis G, Fraison J-B, 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 (2017) A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren’s syndrome. Rheumatology 56(3):362–370. https://doi.org/10.1093/rheumatology/kew376 CrossRefPubMedGoogle Scholar
- 16.Bossini N, Savoldi S, Franceschini F, Mombelloni S, Baronio M, Cavazzana I, Viola BF, Valzorio B, Mazzucchelli C, Cattaneo R, Scolari F, Maiorca R (2001) Clinical and morphological features of kidney involvement in primary Sjogren’s syndrome. Nephrol Dialysis Transpl 16(12):2328–2336CrossRefGoogle Scholar
- 36.Ramos-Casals M, Brito-Zeron P, Seror R, Bootsma H, Bowman SJ, Dorner T, Gottenberg JE, Mariette X, Theander E, Bombardieri S, De Vita S, Mandl T, Ng WF, Kruize A, Tzioufas A, Vitali C, Force ESST (2015) Characterization of systemic disease in primary Sjogren’s syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements. Rheumatology 54(12):2230–2238. https://doi.org/10.1093/rheumatology/kev200 CrossRefPubMedGoogle Scholar
- 37.Hu ZD, Sun Y, Guo J, Huang YL, Qin BD, Gao Q, Qin Q, Deng AM, Zhong RQ (2014) Red blood cell distribution width and neutrophil/lymphocyte ratio are positively correlated with disease activity in primary Sjogren’s syndrome. Clin Biochem 47(18):287–290. https://doi.org/10.1016/j.clinbiochem.2014.08.022 CrossRefPubMedGoogle Scholar