|Year : 2018 | Volume
| Issue : 3 | Page : 109-112
Renal manifestations of primary Sjogren's syndrome
Thanigachalam Dineshkumar, Murugan Myvizhiselvi, Jeyachandran Dhanapriya, Ramanathan Sakthirajan, Natarajan Gopalakrishnan, T Balasubramaniyan
Institute of Nephrology, Madras Medical College, Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India
|Date of Web Publication||17-Dec-2018|
Institute of Nephrology, Madras Medical College, Rajiv Gandhi Government General Hospital, Chennai - 600 003, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background and Objective: Sjogren's syndrome represents a group of diseases characterized by inflammation and destruction of exocrine glands. Renal involvement in Sjogren's syndrome has been reported in 18.4%–67% of patients. Distal renal tubular acidosis (RTA) was reported more common than proximal RTA which can present as acute hypokalemic paralysis. The aim of the present study was to investigate the clinical picture and the outcome in patients with primary Sjogren's syndrome (PSS) with significant renal involvement. Materials and Methods: We conducted a retrospective study of PSS patients with significant renal involvement in our department. Results: A total of 27 patients were included in the study. The mean age was 39.3 ± 4.5 with a mean follow-up of 42 ± 4.8 months. About 18 patients had hypokalemia associated with paralysis, and 4 patients had hypokalemia without paralysis. Female: male ratio was 12.5:1. Number episodes of hypokalemic paralysis range from 1 to 4. The mean time of recovery was 20.4 ± 4 h, and mean potassium requirement was 190 ± 45 mEq intravenously. The mean serum potassium was 2.51 ± 0.55, mean urinary potassium 32 ± 2.3 mEq/day, mean serum bicarbonate 15.03 ± 1.05 mEq/l, and mean blood pH 7.28 ± 0.9. About twenty had distal RTA, and two had proximal RTA. The clinical symptoms were myalgia in 24 (88%), ocular symptoms in 20 (74%), muscular paralysis (66%), oral in 18 (66%), and dental caries in 12 (44%). Five patients underwent renal biopsy of which two showed acute interstitial nephritis, one showed chronic interstitial nephritis, one showed membranoproliferative glomerulonephritis, and one acute tubular injury. Conclusion: The clinical implication of our study is that distal RTA is a common feature of Sjogren's syndrome presenting predominantly as hypokalemic paralysis.
Keywords: Distal renal tubular acidosis, hypokalemia, renal biopsy, Sjogren's syndrome
|How to cite this article:|
Dineshkumar T, Myvizhiselvi M, Dhanapriya J, Sakthirajan R, Gopalakrishnan N, Balasubramaniyan T. Renal manifestations of primary Sjogren's syndrome. J Integr Nephrol Androl 2018;5:109-12
|How to cite this URL:|
Dineshkumar T, Myvizhiselvi M, Dhanapriya J, Sakthirajan R, Gopalakrishnan N, Balasubramaniyan T. Renal manifestations of primary Sjogren's syndrome. J Integr Nephrol Androl [serial online] 2018 [cited 2019 May 20];5:109-12. Available from: http://www.journal-ina.com/text.asp?2018/5/3/109/247691
| Introduction|| |
Sjogren's syndrome is a chronic autoimmune disease characterized by destructive lymphocyte infiltration of the salivary and lacrimal glands resulting in dry eyes and dry mouth. The clinical features include myalgia, muscular weakness, hypoventilation, and complete paralysis. Renal involvement includes most commonly occurring the histological appearance of tubulointerstitial nephritis and less often glomerular involvement. Sjogren's syndrome may occur alone primary Sjogren's syndrome (PSS) or in association with other autoimmune disorders (secondary Sjogren's syndrome). We aimed to document the renal involvement in PSS patients.
| Materials and Methods|| |
We did a retrospective analysis of renal involvement in PSS patients. Patients were classified as having PSS using the 2002 American–European consensus group (AECG) classification criteria which require four of the following: ocular symptoms (dry eyes every day for more than 3 months and/or use of tear substitutes more than three times a day); oral symptoms (daily feeling of dry mouth more than 3 months, recurrent swelling of the salivary glands, or use of liquids to aid in swallowing of dry foods); ocular signs (positive Schirmer's test or a Rose Bengal score of at least 4 of 9); histopathology with a focus score of 1 in a minor salivary gland biopsy; salivary gland involvement documented by a positive result in salivary scintigraphy, parotid sialography, or salivary flow testing; and presence of autoantibodies to Sjogren's syndrome-associated antigen A (SSA [Ro]) and Sjogren's SSB (SSB [La]). The positive predictive value of the AECG criteria is between 54% and 77% and the negative predictive value is between 94% and 98% as compared to the classification criteria of 1986. We excluded the patients with diabetes, systemic lupus erythematosus/overlap, and secondary Sjogren's syndrome.
The clinical presentation of renal disease was reviewed, including symptomatology, laboratory evidence of renal dysfunction (renal tubular acidosis [RTA], proteinuria defined as >300 mg/24 h, hypocalcemia, and hypokalemia), medical comorbidities (diabetes mellitus and hypertension), and estimates of renal function and renal biopsy if needed. The clinical included were gender, age, duration from onset to diagnosis, duration of PSS, renal involvement, first starting symptom, glandular and extraglandular symptoms, medications, history of urinary tract infection, and urinary lithiasis. Laboratory investigations done were urine analysis, 24-h urinary protein, urinary calcium, urinary phosphorus, urinary uric acid, complete hemogram, blood urea, serum creatinine, serum electrolytes, calcium, phosphorus, magnesium, uric acid, liver function tests, urine culture, ultrasound abdomen, serum antinuclear antibody, antidouble-stranded DNA, serum SSA, and SSB.
RTA was diagnosed when patients with hyperchloremic metabolic acidosis with normal anion gap in the absence of gastrointestinal loss of potassium were found to have a urine pH more than 5.5. Distal RTA is diagnosed, when the urine pH fails to acidify < 5.5. The diagnosis of proximal RTA is supported by the presence of glycosuria, aminoaciduria, and phosphaturia. A labial gland biopsy and Schirmer's test were performed in all. Renal biopsy was done when proteinuria was >1.0 g/day, and serum creatinine was >1.5 mg/dL. Details of treatment and its response were included.
| Results|| |
A total of 27 patients were included in the study. The mean age was 39.3 ± 4.5 with a mean follow-up of 42 ± 4.8 months. About 18 patients had hypokalemia associated with paralysis, and 4 patients had hypokalemia without paralysis. Female: male ratio was 12.5:1. Number episodes of hypokalemic paralysis range from 1 to 4. The mean time of recovery was 20.4 ± 4 h and mean potassium requirement was 190 ± 45 mEq intravenously. The most common signs and symptoms and laboratory investigations were given in [Table 1]. Hypertension was seen in one and renal calculi in 4. Only five patients underwent renal biopsy of which two showed acute interstitial nephritis (AIN) [Figure 1], one had chronic interstitial nephritis (CIN) [Figure 2], one had membranoproliferative glomerulonephritis, and one had an acute tubular injury.
|Table 1: Clinical and laboratory parameters of primary sjogren's syndrome patients (n=27)|
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|Figure 2: Renal biopsy showing chronic interstitial nephritis (PAS stain)|
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| Discussion|| |
PSS is a systemic autoimmune disease with a population prevalence of about 0.5% and female preponderance (female: male ratio of 9:1). Extraglandular manifestations include cutaneous, musculoskeletal, pulmonary, renal, hematological, and neurological involvement. Antibodies against SSA are found in 50% and SSB in 40%–50% of patients with PSS, and these antibodies do not reflect the disease activity., The pathogenesis of PSS is not well understood but increased activation of B-cells followed by immune complex formation, and autoantibody production is thought to play important roles. The predominant infiltrating cells are CD4+ T-cells followed by CD8+ T-cells, B-cells, and macrophages.,, Katsifis et al. demonstrated increased levels of the cytokines required for Th17 proliferation and the predominant cytokine interleukin-17 levels seemed to correlate with the severity of the histological lesion.
Renal involvement in PSS was first described in the 1960s with typical tubular defects. Two distinct pathophysiological processes were found as follows: epithelial disease with a predominantly mononuclear lymphocytic infiltration resulting in tubulointerstitial nephritis and nonepithelial disease with a secondary immune complex-mediated process resulting in glomerulonephritis., Pokorny et al. reported renal involvement of 15 of the 65 PSS patients. Tubulointerstitial nephritis was the most common presentation and was characterized by distal RTA in 91% followed by proximal RTA. Severe hypokalaemia, nephrolithiasis, nephrocalcinosis, and chronic kidney disease (CKD) were among SS-associated distal RTA complications. Takemoto et al. found that patient with Sjogren's syndrome with distal RTA had high levels of anti-carbonic anhydrase antibodies against carbonic anhydrase in cortical collecting ducts.
Glomerulonephritis associated with PSS is a rare occurrence that tends to develop late in the course of the disease. The proposed mechanism includes deposition of immune complexes formed by cryoprecipitating monoclonal immunoglobulin M (IgM) along with polyclonal IgG and IgA, but the glomerular disease may also occur in the absence of circulating cryoglobulins leading to membranous or membranoproliferative lesions., Skopouli et al. indicated that palpable purpura, decreased C4 complement concentration, and mixed monoclonal cryoglobulinemia were significant predictors for the development of glomerulonephritis with PSS.
In a study by Maripuri et al., 17 of 24 had tubulointerstitial nephritis (CIN in 11 and AIN in 6). Two had cryoglobulinemic glomerulonephritis, and two had focal segmental glomerulosclerosis. Sixteen were followed after biopsy for more than 12 months and 14 patients maintained or improved renal function through follow-up. Of the seven patients presenting in Stage IV CKD, none progressed to Stage V with treatment. In other study, 35 patients with PSS (4.9%) had clinically significant renal involvement. Thirteen patients (37.1%) had interstitial nephritis alone, 17 patients (48.6%) had glomerulonephritis alone, and 5 patients (14.3%) had both. Nine patients died (25.7%), 11 patients developed CKD (31.4%), and 9 patients developed lymphoma (25.7%). Patients with PSS with renal involvement compared to those without renal involvement (P < 0.0001) had increased mortality.
Patients with PSS should be managed by a multidisciplinary team including rheumatologist, ophthalmologist, dentist, and nephrologist. Xerophthalmia can be usually managed with teardrops and ocular lubricating ointments, and in severe refractory dryness, cyclosporine 0.05% ointment can be used. Patients with dry mouth can be managed by doing gustatory stimulation (chewing gum) and moisture replacement.
Treatment for renal involvement depends on the clinical manifestations. Correction of hypokalemia and alkaline replacement to keep the serum K+ levels normal and serum HCO3 levels at >18 mEq/L are the standard therapy of RTA. Daily life-long alkali replacement in a dose of 1–2 mEq/kg prevents acute hypokalemia as well as the chronic complications of osteomalacia and nephrolithiasis.,, Methotrexate is the mainstay of uncomplicated PSS, steroids, antiproliferative agents, calcineurin inhibitors, and biologic agents (e.g., rituximab (RTX), secukinumab, an anti-IL17 antibody) which has been used to manage resistant cases. In CryoVas study which included 242 cases of noninfectious vasculitis (25% due to PSS), treatment with RTX and corticosteroids was superior to either corticosteroids alone or corticosteroids in combination with an alkylating agent.,
The renal prognosis in patients with PSS and TIN or glomerular disease is usually favorable, but the risk of CKD remains high in patients with TIN. Regular screening is advocated in patients with PSS to facilitate the early detection of renal involvement and prevent its complications. This study validates the observation that hypokalemic paralysis in Sjogren's syndrome may precede classical clinical description and can serve as the clinical marker for the diagnosis. In case of significant proteinuria or deteriorating renal function, a kidney biopsy should be considered before prescribing corticosteroids or other immunosuppressive drugs.
| Conclusion|| |
Our study validates that distal RTA as a common feature of Sjogren's syndrome presenting predominantly as hypokalemic paralysis.
We would like to thank Dr. Anila Abraham Kurien Renopath, Chennai, for her help in evaluating renal biopsy
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]