Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome

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.

One year in review 2021: Sjögren's syndrome

“…Renal involvement represents a quite common extra-glandular complication in SS patients with a prevalence ranging from 2% to 40% according to cohort analysed and diagnostic methods. Moreover, manifestations related to renal involvement are highly variable and several factors, as anti-SSB antibodies and early-onset disease, have been associated with higher risk of kidney involvement in these patients (80)(81)(82). Development of renal complication during disease course may affect patient prognosis and is associated with severe disease, systemic multiorgan involvement.…”

Hypocitraturia as a biomarker of renal tubular acidosis in patients with Sjögrens disease

“…[10][11][12][13][14][15][16] . Some TIN biomarkers have been evaluated to obtain an early marker of renal impairment in patients with SD, with emphasis on b-2 microglobulin, a1 microglobulin, and urinary citrate; however, there is a lack of robust scienti c evidence to prove its e cacy as predictors of nephritis [17][18][19][20][21] . A correlation was also observed between renal involvement with anti-SSB/La positivity 22 or even increased serum IgG and renal involvement 23 .…”

Primary Sjögren’s syndrome with renal tubular acidosis and central pontine myelinolysis: An unusual triad

“…The diagnosis of pSS utilizes the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, which incorporates a combination of clinical and laboratory characteristics [ 5 ]. The EULAR recommends screening people with pSS for kidney disease utilizing the EULAR Sjögren’s syndrome disease activity index (ESSDAI) [ 6 ]. The presence of anti-Sjögren’s-syndrome-antigen B (anti-SSB) antibodies and rheumatoid factor may be associated with more systemic disease, including kidney involvement [ 6 ].…”

“…The EULAR recommends screening people with pSS for kidney disease utilizing the EULAR Sjögren’s syndrome disease activity index (ESSDAI) [ 6 ]. The presence of anti-Sjögren’s-syndrome-antigen B (anti-SSB) antibodies and rheumatoid factor may be associated with more systemic disease, including kidney involvement [ 6 ]. In pSS, kidney manifestations are unusual but important to recognize.…”