Effect of anti-tumor necrosis factor alpha treatment of rheumatoid arthritis and chronic kidney disease

Abstract

Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by elevated inflammatory mediators such as tumor necrosis factor alpha (TNF-α), the impact of anti-TNF-α therapy on progression of CKD in patients with rheumatoid arthritis (RA) is unclear. Seventy patients with RA and CKD were retrospectively analyzed. Outcomes were evaluated using the difference in the annual change of estimated glomerular filtration rate (eGFR) between patients treated with anti-TNF-α or without. Anti-TNF-α therapy significantly decreased disease activity score (DAS) 28 from 5.32 ± 0.78 to 3.59 ± 0.85 (p < 0.001). There was a tendency toward stabilization of eGFR after a mean of 2.9 ± 1.1 years from 50.3 ± 8.4 ml/min/1.73 m(2) to 54.5 ± 16.0 ml/min/1.73 m(2) in patients received anti-TNF-α therapy along with decreased DAS28 (p = 0.084). Conversely, eGFR decreased significantly in patients not receiving anti-TNF-α therapy after a mean of 2.8 ± 1.7 years from 52.6 ± 7.5 ml/min/1.73 m(2) to 46.5 ± 11.5 ml/min/1.73 m(2) (p = 0.041) without significant DAS28 change (p = 0.078). The annual change of eGFR was significantly different between patients treated with anti-TNF-α drugs and without (2.0 ± 7.0 ml/min/1.73 m(2)/year vs. -1.9 ± 4.0 ml/min/1.73 m(2)/year; difference in mean vs. -3.9 ± 7.3 ml/min/1.73 m(2)/year; p = 0.006). Use of anti-TNF-α drugs was significantly associated with positive annual change of eGFR in multivariate logistic regression analysis (p = 0.019). Among patients with RA and CKD, treatment with anti-TNF-α drugs was associated with less renal function decline. Anti-TNF-α drugs may be beneficial for managing RA combined with CKD.

Increased Risk of Chronic Kidney Disease in Rheumatoid Arthritis Associated with Cardiovascular Complications – A National Population-Based Cohort Study

“…Accumulating data reveal that CKD is more prevalent in patients with chronic inflammatory disorders, such as psoriasis [ 17 , 18 ] and ankylosing spondylitis [ 19 ], compared to the general population. Systemic inflammation may contribute to progressive loss of kidney function and anti-inflammatory drugs, such as TNF-α antagonists, have therapeutic potential in preventing CKD progression in RA [ 20 , 21 , 22 ]. Concerning comorbidities in CKD, Daoussis and coworkers showed renal dysfunction to be strongly associated with classic CV risk factors [ 13 ].…”

Inflammatory Cytokines as Uremic Toxins: “Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son”

“…Agents include anti-TNFα monoclonal antibodies (infliximab, adalimumab, golimumab), antigen-binding fragment (Fab’: certolizumab) and a soluble TNFα receptor (sTNFR: etanercept) [40]. Interestingly, in patients with rheumatoid arthritis and CKD the use of anti-TNF therapies was associated with slower loss of GFR, although it is unclear whether this is the result of interfering with rheumatoid arthritis disease activity or with CKD-associated progression of kidney injury [41]. In CKD, circulating levels of TNFα are well within the range found in rheumatoid arthritis patients treated with infliximab [42].…”

YB-1 Interferes with TNFα–TNFR Binding and Modulates Progranulin-Mediated Inhibition of TNFα Signaling

“…Tumor necrosis factor α (TNFα) promotes inflammation and tissue-destruction in a number of inflammatory diseases, including glomerulopathies [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. TNFα acts through two distinct receptors.…”

“…Treatment of rheumatoid arthritis patients with TNFα-blocking drugs improved clinical symptoms. Patients who also suffered from chronic kidney disease demonstrated a beneficial effect on kidney function [ 24 ]. Although all anti-TNFα therapies have well-demonstrated efficacy, the increased risk of lymphomas or reactivation of latent infection remains a drawback [ 32 , 33 , 34 , 35 , 36 ].…”