A 42-year-old patient was admitted to the university hospital of Göttingen, Germany, because of an increase in serum creatinine level to 2.85 mg/dL (251.94 µmol/L) 18 months after initiation of adalimumab therapy. Estimated glomerular filtration rate (eGFR) was 26 mL/min/1.73 m2
(0.43 mL/s/1.73 m2
) calculated using the 4-variable isotope-dilution mass spectrometry–traceable Modification of Diet in Renal Disease (MDRD) Study equation.5
Ankylosing spondylitis had been diagnosed 6 years before the patient’s admission. His symptoms had included recurring bilateral iritis and bilateral pain of the sacroiliac joints. HLA-B27 assay results had been positive. Radiographic studies at that time had shown signs of sacroiliitis. He had been treated initially with oral ibuprofen at a dose of 600 mg once daily and sulfasalazine, 500 mg, twice daily. Sulfasalazine was stopped after 3 months because of gastrointestinal adverse events. Disease flares with pain in both ankles, cervical spine, or shoulders occurred every 5 to 6 months, during which he reported intake of up to 600 mg of ibuprofen 3 times daily. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, a subjective measurement of disease activity with a score of 0–10, in which 10 represents the highest activity) score was calculated, with a score of 8.05 at initial presentation to his rheumatologist. Adalimumab therapy was started at a dose of 40 mg every other week 18 months before admission to our hospital because of lack of improvement with conventional therapy. Adalimumab treatment was well tolerated and resulted in a significant improvement in lower-back pain. BASDAI score improved from 8.05 to 2. Ibuprofen was taken about every 4 weeks after switching to adalimumab therapy.
At the time of admission, the patient’s symptoms included mild lower-back pain and pain in the wrists and knees that occurred mainly in the early morning hours and lasted for less than 1 hour. Adalimumab therapy was discontinued at the time of admission, and the patient was advised not to use ibuprofen any longer.
Physical examination showed blood pressure of 150/90 mm Hg. There was no evidence of lymphadenopathy or lacrimal gland enlargement. The parotid glands were slightly tender to palpation without enlargement. Ophthalmic examination showed bilateral uveitis with bilateral periphlebitis.
Initial laboratory studies showed the following values: increased creatinine level, 2.85 mg/dL (251.9 µmol/L; reference range, 0.55–1.02 mg/dL [48.6–90.2 µmol/L]), which had been 0.86 mg/dL (76.0 µmol/L) 3 months before admission; serum urea nitrogen, 23 mg/dL (8.21 mmol/L; reference range, 6–25 mg/dL [2.14–8.93 mmol/L]); eGFR, 25 mL/min/1.73 m2 (0.41 mL/s/1.73 m2); angiotensin-converting enzyme, 21.9 IU/L (reference range, 8.3–21.4 IU/L); antinuclear antibody, positive at a titer of 1:320 (reference range, < 1:80; antinuclear antibody had not been present before the initiation of adalimumab treatment); double-stranded DNA and anti–glomerular basement membrane antibodies, negative; and C3, within the reference range. Urine examination showed no eosinophils, casts, or proteinuria.
Chest radiograph showed new bilateral hilar adenopathy (Fig S1
, provided as online supplementary material) compared with the radiograph before the initiation of adalimumab therapy. Renal ultrasonography showed normal-sized kidneys with normal parenchyma.
Treatment with prednisone was initiated at a dose of 0.5 mg/kg of body weight because the diagnosis of sarcoidosis/sarcoid-like illness was suspected based on clinical grounds. The dosage gradually was decreased to a maintenance dose of 15 mg once daily. Ramipril was added at a dose of 10 mg/d because of persistently increased blood pressure.
A left kidney biopsy () was performed after 2 months because of deterioration in kidney function. The biopsy specimen of the renal cortex with 7 glomeruli showed normal glomerular architecture. In the interstitium, compact infiltration with mononuclear cells was seen, consisting of mostly lymphocytes and epithelioid macrophages focally organized in small well-delineated noncaseating granulomata. Within these interstitial areas, tubuli often were collapsed. In other less inflamed areas, tubules showed regular segmental differentiation. The interstitium was slightly edematous and showed a small matrix increase. Staining for acid-fast bacilli and fungi was negative.
Figure 1 Kidney biopsy of the patient. (A) Dense infiltration of the interstitium with mononuclear cells consisting in part of lymphocytes and epithelioid macrophages that are organized in small granulomata (arrowheads). Tubules are compressed by the interstitial (more ...)
Immunohistochemistry of glomeruli showed slight mesangial positivity for C1q and immunoglobulin M (IgM); C3, fibrinogen, IgA, and IgG were negative. Electron microscopy showed a glomerulus with normal basement membranes and regular foot processes of podocytes; there were no dense or immune deposits in the mesangium or along the glomerular basement membranes.
At 1 year of follow-up, kidney function had improved (), creatinine level was 1.44 mg/dL (127.3 µmol/L), serum urea nitrogen level was 16 mg/dL (5.71 mmol/L), and eGFR was calculated as 57 mL/min/1.73 m2 (0.95 mL/s/ 1.73 m2). Lower-back pain and pain of the wrists and ankles flared under isolated therapy with prednisone. Finally, treatment of ankylosing spondylitis with infliximab at a dose of 5 mg/kg of body weight was initiated, and at present, kidney function remains stable after 3 infusions of infliximab, with creatinine level of 1.67 mg/dL (147.63 µmol/L) and eGFR of 48 mL/min/1.73 m2 (0.80 mL/s/1.73 m2).
Figure 2 The patient’s creatinine levels, urinary protein concentration, and sequence of events during 16 months of follow-up. Prednisone treatment was begun 3 days after admission to the hospital. Kidney biopsy was performed 2 months after initial presentation. (more ...)