Kidney Issues Should be Considered While Using TNF-Alpha Inhibitors

Despite being rare, kidney complications should be considered in patients with ankylosing spondylitis treated with inhibitors of tumor necrosis factor-alpha (TNF-alpha), such as Remicade (infliximab), according to a case report.

The study, “Infliximab-associated focal segmental glomerulosclerosis in a patient with ankylosing spondylitis,” was published in Rheumatology International.

Ankylosing spondylitis (AS) is a debilitating type of arthritis that mainly affects the joints of the spine, causing chronic pain and lifelong physical disability.

One of the treatment options currently available is the use of inhibitors that block the activity of TNF-alpha, a signaling molecule involved in immune and inflammatory responses that is produced in excessive amounts in AS patients.

“Infliximab [Remicade] is a monoclonal antibody to human tumor necrosis factor-alpha that has potent anti-inflammatory activity and is approved in the therapy of rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriasis, and inflammatory bowel disease (IBD),” the researchers said.

“Although there are known common TNF inhibitor (TNFi)-associated complications including infection and increased risk of lymphoma, very rare complications attributed to these drugs have begun to be recognized with their increased use, including … renal complications,” they added.

In this case report study, researchers from the Dokuz Eylul University School of Medicine (Turkey) described the case of a patient with AS who developed focal segmental glomerulosclerosis (FSGS; a disease in which the filtering units of the kidney are damaged) associated with Remicade treatment.

At admission, the 40-year old woman complained of groin and back pain, especially during the night, and morning stiffness for the past two months. After undergoing physical examination and imaging tests with X-rays and magnetic resonance imaging (MRI), she was diagnosed with AS.

Biochemical analyses revealed the levels of C-reactive protein (CRP, a protein involved in inflammation) were abnormally high (16.4 mg/L, while normal levels range between 0.2–5 mg/L); no abnormalities were found in her urine.

After unsuccessful treatment with diclofenac, Azulfidine (sulphasalazine), methotrexate (MTX), methylprednisolone, indomethacin and etanercept, she was started on Remicade. After three months of treatment she started showing signs of improvement. However, six months after starting treatment with Remicade, a spot urine test detected the presence of microscopic amounts of protein (proteinuria) and blood (hematuria) in her urine.

“When asymptomatic proteinuria and microscopic hematuria were diagnosed, [infliximab, non-steroidal anti-inflammatory drugs, and sulphasalazine] were stopped and the patient subsequently underwent a percutaneous (needle puncture of the skin) renal biopsy,” the researchers said.

Biopsy results showed a series of kidney abnormalities that were consistent with focal segmental glomerulosclerosis. After conducting a systematic review of the literature between 1990 and 2018, researchers found that although previous studies had already reported the occurrence of kidney complications associated with Remicade in AS patients, this was the second reported case of FSGS linked to Remicade.

“In conclusion, TNFi-induced adverse events should be considered when physicians come across unexpected conditions in patients taking TNFi therapy. Although renal complications of TNFi are uncommon … spot urine evaluation may be recommended in the follow-up of patients treated with TNFi. Kidney biopsy should not be delayed if necessary. When renal pathology is diagnosed, or even suspected, the TNFi should be stopped and the patient should be treated according to the clinical manifestations and biopsy findings,” they concluded.