A 49-year-old man was diagnosed as having esophageal carcinoma (PT3N3M0, Stage IV) in December 2020. Radical resection of midpiece esophageal carcinoma was performed, and chemotherapy with "paclitaxel (albumin-bound) + oxaliplatin" was given for four courses. In November 2021, chemotherapy combination with immunotherapy (tislelizumab 200 mg on day 1 + docetaxel 100 mg on day 2 + nedaplatin 100 mg on day 3) was given due to multiple lymph node metastasis in the mediastinum and posterior peritoneum. The date of the last chemotherapy was 28 June 2022. He did not have a medical history of hypertension, diabetes, or kidney disease.
He complained of gross hematuria, pollakiuria, painful micturition, and low back pain after six courses of tislelizumab (PD-1 mAb). Physical examination: T (Temperature) 36.4 C, P(Pulse) 85 bpm(beats per minute), R (Respiration) 16 bpm(breaths per minute), BP (Blood pressure) 125/75 mmHg. The abdomen was soft, no tenderness and rebound. His bilateral renal percussive pain was positive. There was no edema in the lower limbs.
Urinalysis showed red blood cells (RBCs) of 4,932/microl, white blood cells (WBCs) of 9,375/microl, and proteinuria 3+. Biomarkers of renal tubular injury showed urinary N-acetyl-beta-d glycosaminidase (NAG) 74.9 U/L (normal range 0.3-12 U/L), urinary neutrophil gelatinase-associated lipocalin (NGAL) 537.6 U/L (normal range 0.9-82 U/L), urinary albumin/creatinine 1,731.5 mg/g, urinary transferrin 1.74 mg/dl (normal range 0-0.2 mg/dl), and alpha1-microglobulin 0.95 mg/dl (normal range 0-1.25 mg/dl). Blood routine test showed that transient eosinophilia increased. Blood tests showed WBCs of 4,500/microl (neutrophils 35.6%, eosinophils 17%), lactate dehydrogenase 218 U/L, serum creatinine (sCr) 167 micromol/l (baseline sCr 81.7 micromol/l), erythrocyte sedimentation rate (ESR) 41 mm/h, and C-reactive protein <0.5 mg/L. The autoimmune antibody profile, immunoglobulin profile, and complement level were within normal range. Serum IgG4 was 0.497 g/l (normal range 0.03-2.01g/l). Fungal D-glucan test was negative. Serum procalcitonin was negative. Serum T-spot and urinary Mycobacterium tuberculosis were negative. Antibiotics were given, yet urinary symptoms were not relieved. His sCr level was significantly elevated to 211 micromol/l (baseline sCr 81.7 micromol/l). Blood tests showed that C-reactive protein was 41.7 mg/L; ESR was 120 mm/h. Repeated urine cultures were negative. Bilateral ureteral stenting was performed, and cystoscopy revealed diffused redness of the bladder mucosa, no sign of carcinoma infiltration. The pathologic change of the bladder tissue showed effacement of the bladder urothelium, hyperplastic granulation tissue, and infiltration of monocytes, lymphocytes, plasmacytes, and neutrophils in the bladder tissue. Immunohistochemistry staining of the bladder tissue showed positive staining of CD3, CD8, CD20, and CD117, yet negative staining of CD68, TIA-1, and PD-L1 in focal lesions ( Figures 1A-F ). The metagenomic next-generation sequencing (mNGS) of urine and ureter-bladder tissues was negative. Urinary ultrasonography and computed tomography showed mild hydronephrosis, dilated ureter, and thickened bladder wall ( Figures 2A-C ). Bladder residual urine was negative. The patient was eventually diagnosed as having immune-related ureteritis and cystitis on the 13th week after the occurrence of urinary symptoms. Methylprednisolone was administered at 60 mg (body weight 50 kg, equivalent to 1.5 mg/kg/day of prednisone) intravenously, and urinary irritation symptoms were relieved quickly after 3 days of treatment. After 2 weeks of methylprednisolone, sCr returned to the baseline level, and urinary WBC/RBC turned negative after 3 weeks of glucocorticoid therapy. Methylprednisolone was tapered gradually. Since the patient had a recurrence of urinary irritation symptoms, gross hematuria, and sterile pyuria on 16 September, methylprednisolone was increased to 40 mg intravenously, and the urinary irritation symptoms were alleviated quickly and urinary analysis improved. Bilateral ureteral stents were removed on 10 October 2022. The current dose of prednisone tablets is 25 mg. His urinary analysis showed that WBC was 145/mul, RBC was 5/mul, and sCr was 89.7mumol/l on 17 October 2022. The timeline of the treatment course was summarized in  Figure 3 .