A 33-year-old man was referred to our rheumatology department in 2003 because of low back pain accompanied by tenderness of the knees and small joints of the wrists. Since the axial pattern of affection dominated the clinical presentation at that time and the patient was HLA B27 positive, he was diagnosed with ankylosing spondylitis with accompanying peripheral arthritis. Low-dose glucocorticoids and methotrexate (15 mg weekly) were introduced, leading to significant improvement of signs and symptoms, as well as decline in the number of swollen and tender peripheral joints within the following months. Basal blood pressure values were normal (128/76 mmHg) while the estimated glomerular filtration rate (eGFR) was 99.8 mL/min/1.73 m2.
Despite initial improvement, the following time course was marked by aggravation of signs and symptoms consistent with peripheral polyarthritis, leading to a diagnosis of seronegative RA in 2005, fulfilling the 1987 classification criteria. Methotrexate was continued, now in combination with sulfasalazine (2 grams daily) being replaced with leflunomide (20 mg daily) after several months. Despite combined treatment with conventional disease-modifying agents (DMARDs) and concomitant use of low-dose glucocorticoids, the patient suffered from a persistently active disease with a 28-joint disease activity score calculated using the erythrocyte sedimentation rate, ESR (DAS28-ESR) of 5.52. This prompted the initiation of adalimumab (40 mg subcutaneous every other week), while methotrexate was continued at a lower dose (10 mg weekly). This treatment strategy led to a satisfactory clinical response and reduction of DAS28-ESR to 2.66.
In 2006, the patient developed a psoriatic rash of the palms and soles, which was successfully treated with topical therapy. In the same year, the patient developed arterial hypertension (175/94 mmHg), for which an ACE inhibitor was introduced.
In 2011, the patient was still in stabile remission of his rheumatic condition (s) while continuously taking the biological drug; however, routine urinalysis unexpectedly revealed microscopic hematuria (urine sediment E 20-30 erythrocytes and 66-73% dysmorphic erythrocytes), accompanied by non-nephrotic proteinuria (2.25 g in daily urine, dU) with eGFR of 56 mL/min/1.73 m2. Urine cytology revealed no urothelial atypia, and urine was negative for M. tuberculosis. The erythrocyte sedimentation rate (ESR) was increased (64 mm/h) as well as the C-reactive protein (CRP) level (18.3 mg/L). The complete blood count was unremarkable, as well as blood urea nitrogen (BUN) (5.0 mg/dl) and serum electrolytes. Serum creatinine was increased (137 mumol/l), as well as total cholesterol (5.7 mmol/L), LDL-cholesterol (3.52 mmol/L), and triglycerides (2.78 mmol/L). Antinuclear, anti-neutrophil cytoplasmic, and anti-glomerular basement membrane antibodies (ANA, ANCA, and GBM, respectively) were negative. Serum protein electrophoresis, immunoelectrophoresis, and immunofixation were normal as well as serum complement levels (C3 and C4). Screening for hepatitis B, hepatitis C, and HIV (human immunodeficiency virus) were negative. On ultrasonography, both kidneys were of normal size with hyperechogenic parenchyma.
Percutaneous kidney biopsy was performed, and its results are shown in Figures 1(a) and 1(b).
On light microscopy, diffuse mesangial hypercellularity was observed in all glomeruli, whereas global sclerosis was established in 1 of 15 glomeruli (6.66%). The tubules demonstrated degenerative changes while there were no changes on arteries. A moderate mononuclear infiltrate and mild fibrosis was noted in the interstitium. Immunofluorescence microscopy revealed mild mesangioproliferative changes. Electronic microscopy showed eosinophil infiltrates mostly in the mesangium, while several subendothelial and subepithelial eosinophil deposits were seen in the capillaries. In some glomeruli, there were signs of podocyte loss. Electronic microscopy also revealed glomerulonephritis with diffuse mesangial deposits and several subendothelial and subepithelial deposits compliant with glomerulonephritis caused by circulating immune complexes. The findings were in concert with the diagnosis of IgAN. There were no elements of diabetic nephropathy. The patient's MEST-C score was M1, E0, S1, T2, and C0.
Treatment with adalimumab and medium-dose glucocorticoids (prednisone 20 mg) was continued as well as an ACE inhibitor. Over the next two years, the patient was in a state of low disease activity (DAS28 3.08) of his RA, with progression of chronic kidney disease (eGFR 35.3 mL/min/1.73 m2) and persistent proteinuria (2.26 g/dU). This prompted discontinuation of adalimumab and a further increase in the dose of glucocorticoids (prednisone 60 mg), with the intention to control the renal disease.
Due to the increased prednisone dose, the patient gradually developed cushingoid features including type 2 diabetes mellitus; he was diagnosed in 2014. A slight improvement in kidney function (eGFR 44.1 mL/min/1.73 m2) and proteinuria (1.60 g/dU) allowed for a reduction of the prednisone dose to 40 mg. Of note, the patient's blood pressure was unremarkable, often being 120/80 mmHg or even less.
In 2015, the patient's kidney function was without further deterioration (eGFR 42.2 mL/min/1.73 m2) and without progression of proteinuria. Diabetes was not adequately controlled, and the patient also experienced a relapse of his RA; so, rituximab was introduced in 2016. Unfortunately, the drug had to be discontinued after three cycles due to lacking efficacy and an increase in proteinuria from 0.78 to 2.04 g/dU. After discontinuation of rituximab, a decision was made to commence treatment with baricitinib, an oral selective JAK inhibitor. This finally led to the achievement of a low disease activity state of RA. However, the patient still continued to have persistent proteinuria of 1.9 g/dU, with no further decline in the eGFR.