Reversible proteinuria after adalimumab discontinuation in a patient with Crohn's disease.

Sir,

Renal complications are not infrequent in patients with inflammatory bowel diseases and seem to be more prevalent in patients with Crohn's disease. The spectrum of renal complications in Crohn's disease patients involves nephrolithiasis, amyloidosis, renal hypertension, glomerulonephritis (from minimal change nephropathy to rapidly progressive crescentic), tubulointerstitial abnormalities and iatrogenic complications related to medications such as aminosalicylates and cyclosporine.

Anti-tumour necrosis factor (anti-TNFa) agents, including adalimumab, constitute a new generation of biological agents used in the treatment of a variety of autoimmune diseases such as rheumatoid and psoriatic arthritis, ankylosing spondylitis and Crohn's disease. We report herein a Crohn's disease patient diagnosed with proteinuria that was totally reversed after discontinuation of adalimumab.

A 38-year-old male with terminal ileum Crohn's disease diagnosed 6 months previously was admitted to our hospital due to a relapse. Before admission, the patient was administered methylprednisolone 32 mg/day with sub-optimal response. On admission, the patient underwent routine screening to exclude underlying infection prior to prescription of anti-TNF-α agents. Subsequently, the patient was started on adalimumab induction scheme (160 mg subcutaneously). Two weeks afterwards, the patient complained of lower limb oedema, and laboratory screening revealed proteinuria of 1600 mg/day without any evidence of other extraintestinal comorbidity. Adalimumab was discontinued and patient was followed up. Proteinuria resolved completely 4 weeks after adalimumab discontinuation, but we decided no adalimumab rechallenge and no renal biopsy. The patient was started on therapy with azathioprine 150 mg/day and is currently in excellent clinical status.

To the best of our knowledge, this is the first report of a patient with Crohn's disease and adalimumab-associated proteinuria. Treatment with adalimumab may lead to antibody formation, but renal complications are rare and have so far been reported only in 11 patients with rheumatoid arthritis [1-5] but not in patients with inflammatory bowel disease. Of interest, in rheumatoid arthritis patients, proteinuria has also been reported during therapy with other than adalimumab biological agents such as infliximab and etanercept [3].

Renal histology, when performed in rheumatoid arthritis patients with adalimumab-related renal dysfunction, showed patterns of systemic lupus erythematosus-like syndrome [1], necrotizing and crescenting glomerulonephritis [3,5], minimal lesion glomerulopathy [2], extracapillary glomerulonephritis with IgA deposits or active follicular necrosis against a background of glomerular sclerosis [4].

It is noteworthy that, as with this Crohn's disease case, favourable outcomes have been reported in all other rheumatoid arthritis cases. After adalimumab discontinuation and glucocorticoid [4] and/or immunosuppressive therapy [3,5], renal function recovered within a few weeks. Of interest, in one case proteinuria relapsed after adalimumab rechallenge [2].

In this case, the relative contributions of adalimumab and of the underlying Crohn's disease to the development of proteinuria cannot be exactly determined. However, it is questionable whether in this particular patient adalimumab induction scheme was the only factor able to induce proteinuria. We believe that the complete reversibility of proteinuria after adalimumab discontinuation points towards adalimumab as a triggering factor to a strongly predisposed for a renal dysfunction individual.

As there have been some concerns regarding safety issues during administration of anti-TNF-α agents, it is of importance to understand the mechanism(s) of their interference in the normal kidney function. By this way, we may able to properly screen and possibly identify high-risk groups before initiation of anti-TNF-α therapies. For the moment, careful patient selection for biological agents as well as regular follow-up can promptly diagnose and completely reverse rare or unexpected episodes.

Conflict of interest statement. None declared.