In 2018, a 67-year-old Chinese man was admitted to our hospital with dryness of mouth for 6 years and elevated serum creatinine for 2 years. Six years ago, he felt dryness of mouth. Enlargement of salivary gland were discovered, and resection of bilateral submandibular gland was performed. The pathologic examination revealed severe chronic inflammation. Two years ago, the patient felt fatigue. The serum creatinine was 164 mumol/L (corresponding to estimated glomerular filtration rate of 40.2 ml/min/1.73 m2 as calculated by the CKD-EPI equation) with benign urinary analysis. Half a year later, his serum creatinine elevated to 175 mumol/L (corresponding to estimated glomerular filtration rate of 37.5 ml/min/1.73 m2 as calculated by the CKD-EPI equation). Positive antinuclear antibody (ANA) with titer of 1:3,200 was discovered. Oral methyprednisolone was prescribed as 32 mg per day and tapered quickly because of deteriorating dry mouth. After that, his serum creatinine suddenly elevated to 517 mumol/L within 3 months. And he had intermittent facial rash when exposed to the sun.
The patient had tuberculous pleurisy 50 years ago and fully recovered. Family history was of no significance.
On admission, physical examination revealed blood pressure of 125/70 mmHg, temperature of 36.3 C, pulse of 75 beats/min, and respiratory rate of 15/min. His tongue was dry, and dental caries could be found.
Laboratory data were as follows. Urinary analysis showed proteinuria+, glucose+ with normal blood glucose. Urine sediment analysis revealed red blood cell 0-2 cells per high power field (HPF) with white blood cell 0-1/HPF. Urinary protein excretion was 1.00 g/24 h (urine volume 2,700 ml). The urinary alpha 1 microglobulin was 343 mg/L (normal range: 0.00-12.00 mg/L) and N-Acetyl-D-Glucosaminidase 22 IU/L (normal range: 0-21 IU/L). Urine osmotic pressure was 314 mOsm/kg with normal blood osmotic pressure. Urine protein electrophoresis showed 58.90% of small molecule protein, 32.9% of albumin, and 8.20% of large molecule protein. Blood routine test showed mild anemia (hemoglobin 95 g/L). Blood chemistry tests showed increased levels of blood urea nitrogen and serum creatinine (16.91 mmol/L and 456.00 mumol/L, respectively). Serological studies revealed a high titer of ANA (1:10,000) and an increased level of anti-dsDNA antibody (>800 IU/ml) with negative ENA. Decreased serum levels of C3 (0.240 g/L) and C4 (<0.017 g/L) were detected. Total IgG was elevated to 33.80 g/L, and IgG subtypes were IgG1 19.8 g/L, IgG2 3.84 g/L, IgG3 2.24 g/L, and IgG4 2.43 g/L. Coombs test was positive.
Tear break-up time (BUT) indicated dryness of eye (<10 s). Labial gland biopsy did not indicate the diagnosis of Sjogren's Syndrome. Submandibular gland pathology revealed severe chronic inflammation of the left submandibular gland. Immunochemistry staining of immunoglobulin showed IgG3 positive.
Percutaneous renal biopsy was performed. Light microscopy examination showed that 3/14 glomeruli were globally sclerosed and 6/14 glomeruli showed ischemic sclerosis. Other glomeruli showed minor shrinkage of glomerular capillary wall, but no significant glomerular change. Tubular epithelial cells exhibited focal vacuolization and eosinophilic granules in the cytoplasm and focal loss of brush border. There were profound interstitial infiltration with lymphocytes, plasma cells, and a few eosinophils. "Storiform" fibrosis with tubular atrophy can be seen in the tubulointerstitium (Figures 1A-C). Immunofluorescence microscopy revealed one out of seven glomeruli with crescent and granular mesangial staining for IgG and C3, and granular staining for IgG, kappa, lambda, IgG1, IgG2, IgG3, IgG4, and C1q along TBM and interstitium and linear staining for lambda also along TBM (Figure 1D). Electron microscopy revealed one glomerulus with numerous electronic dense deposits along tubular basement membrane with focal mesangial deposits (Figure 1E). Immunohistochemistry revealed that IgG1-positive plasma cells were 35-45/HPF, IgG2-positive plasma cells 40-50/HPF, IgG3-positive plasma cells 90-100/HPF, and IgG4-positive plasma cells 10-15/HP (Figures 1F-I). Taken together with the diagnosis of SLE, these findings indicated the renal lesion as predominant acute and chronic tubulointerstitial nephritis with dominant IgG3 positive plasma cell infiltration.
Oral prednisone 30 mg was prescribed immediately. Hydroxychloroquine 0.2 g and mycophenolate mofetil 1.0 g were given later. The serum creatinine was gradually reduced from 456 mumol/L to 210 mumol/L. The urinary protein was reduced to 0.17 g/24 h in 8 months. The patient was stable for the last 31 months during follow-up.