Combination Cyclophosphamide/Glucocorticoids Provide Better Tolerability and Outcomes versus Glucocorticoids Alone in Patients with Sjogren’s Associated Chronic Interstitial Nephritis

Abstract

Background: Steroid therapy has become an effective option for patients with primary Sjogren’s syndrome with tubulointerstitial nephritis (TIN), while the use of cytotoxic agents is still debated. Our study aimed to compare the clinical outcomes of patients treated with cyclophosphamide (CTX) combined with glucocorticoids with those of patients treated with glucocorticoids alone. Methods: All patients with primary Sjogren’s syndrome with chronic TIN admitted to the Division of Nephrology, Ruijin Hospital, from January 1, 2002, to April 30, 2016, and treated with steroids alone or combined with CTX were included. The immunological prognosis, improvements of renal function, and acquired tubular defects of the patients were retrospectively compared between the 2 therapeutic groups. Results: A total of 70 cases were included. Of these, 36 were diagnosed by renal biopsy. A total of 56 patients were treated with glucocorticoids alone, while 14 patients received glucocorticoids combined with CTX. There were no significant differences in clinical characteristics and laboratory parameters between the 2 therapeutic groups at baseline. Compared with patients in the steroid group, patients in the CTX group showed better estimated glomerular filtration rate (eGFR) improvement (21.35 ± 19.63 vs. 2.72 ± 19.11 mL/min/1.73 m², p = 0.006) but a similar decline in immunoglobulin G (IgG; 450 [interquartile range, IQR 910] vs.176 [IQR 1,910] mg/dL, p = 0.93) at 12 months of follow-up. CTX therapy was associated with better eGFR improvement (β = 12.96 [2.95–22.97]) even after adjusting for dry mouth, anti-Sjögren’s-syndrome-related antigen A and anti-Sjögren’s-syndrome-related antigen B positivity, hemoglobin, initial steroid dose, and baseline eGFR by linear regression analyses. Subgroup analyses revealed that the beneficial effects of CTX therapy on renal function were only observed in patients with baseline IgG ≥1,560 mg/dL or eGFR <90 mL/min/1.73 m². The urine α1-microglobulin improvement was better in the CTX group than in the steroid group at 12 months of follow-up (β = 1.29, 95% CI 0.56–2.02, p = 0.001). Conclusions: CTX therapy is suggested for primary Sjogren’s syndrome patients with chronic TIN, especially those with higher IgG levels and abnormal renal function at baseline.

Efficacy and safety of topical and systemic medications: a systematic literature review informing the EULAR recommendations for the management of Sjögren’s syndrome

“…However, a prospective study of 60 patients followed for a mean of nearly 4 years found that corticosteroids did not influence the progressive decrease in salivary flow rates 53. No controlled studies are published in primary-2002 patients, and only retrospective studies have reported the use of GCs for systemic disease,54 with a high rate of GC-related adverse events, including increased appetite and weight gain,52 a two-fold higher frequency of diabetes mellitus55 56 and Cushing in up to 80% of patients 56…”

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

“…119 Tubular interstitial nephritis (TIN) is the most common histological feature in patients with pSS-associated renal disease. 121 In this context, renal biopsies demonstrate marked infiltration by B lymphocytes and plasma cells, 122 similar to that seen in salivary glands. Typically, TIN in pSS is associated with distal renal tubular acidosis (RTA), 118,119,[123][124][125] and may lead to electrolyte imbalance (acidosis, hypokalemia, hypophosphatemia) 122 and rarely periodic paralysis.…”

“…115 Although randomized controlled trials (RCTs) are lacking, corticosteroids and/or immunosuppressive/cytotoxic agents have been used, with anecdotal responses to treat renal disease complicating SS. 121…”

“…199,299 However, anecdotal responses to these agents have been noted in patients with systemic or serious complications of SS; these data are gleaned from retrospective studies and small case series. 121 In CTD-associated ILD, data regarding CS or other IA are limited. 295,[300][301][302] The only RCTs evaluating therapy in CTD have included scleroderma-associated ILD (SAILD).…”

Primary Sjögren syndrome-associated acute interstitial nephritis and type 3 renal tubular acidosis in a patient with thin basement membrane nephropathy

“…The 2 patients had stable eGFR in 5-year follow-up. Shen et al [ 12 ] divided 70 pSS patients with chronic TIN into the corticosteroids (≥15 mg/day) and CTX (0.6–0.8 g/month) combination group (n = 14) and corticosteroids (≥15 mg/day) alone group (n = 56). After 12-month follow-up, the group with combination treatment had better eGFR improvement (21.35 ± 19.63 vs 2.72 ± 19.11 mL/min/1.73m 2 , P = .006).…”