This patient was a 71-year-old male who was receiving nivolumab infusions for treatment of urothelial carcinoma who presents with acute kidney injury. The patient's initial cancer diagnosis was 20 months' prior, and bladder biopsy had revealed high grade carcinoma with lymphovascular invasion. The patient was initially treated with gemcitabine and cisplatin for 4 cycles, followed by radical cystectomy with an ileal conduit. The patient was then initiated on nivolumab infusions which was administered every 28 days. The patient had been responding well with near resolution of hypermetabolic abnormalities on positron emission tomography (PET) scans.
The patient was due for his 16th cycle but experienced night sweats, fatigue, and decreased appetite for 2-3 weeks. The patient's infusion was postponed and was found to have acute kidney injury. Laboratory studies showed a blood urea nitrogen (BUN) of 68 mg/dL, serum creatinine 4.4 mg/dL (from a baseline of 1.2 mg/dL with a baseline glomerular filtration rate (GFR) of 60 mL/min), in addition to new-onset leukocytosis with a WBC of 11.8 K/ul. The patient was sent to the emergency department the following day after repeat labs confirmed these abnormalities.
The patient's evaluation in the emergency department revealed a further decline in his renal function with a serum creatinine now up to 5.4 mg/dL; continued mild leukocytosis and computerized tomography of the abdomen and pelvis without intravenous or oral contrast (CT) revealed perinephric stranding without hydronephrosis or apparent ileostomy malfunction. A urine sample was obtained from the patient's urostomy bag revealing 554 WBCs/hpf, 16 RBCs/hpf, many bacteria, rare WBC clump, and 1+ protein. Urine eosinophil stain was negative. The patient was hemodynamically stable, afebrile, and not particularly ill-appearing. The patient was admitted to the hospital and intravenous normal saline for hydration were initiated and the patient received intravenous Ceftriaxone after blood cultures and urine cultures were obtained.
The patient's home medications were benazepril 10 mg daily, apixaban 5 mg twice a day for atrial fibrillation, and simvastatin 20 mg daily. Urine culture was positive for pan sensitive E. coli. Blood cultures were negative. Despite hydration and intravenous antibiotics, the patient's renal function continued to decline. The patient developed volume overload with small bilateral pleural effusions and hyponatremia. The patient continued to make a fair amount of clear yellow urine throughout his stay but developed oliguria on hospital day 4. Dialysis was initiated on hospital day 5 at which point the patient's BUN and creatinine had risen to 82 mg/dL and 9.6 mg/dL, respectively.
A kidney biopsy was performed to identify the etiology of the patient's acute kidney injury. The biopsy had 17 glomeruli, of which 3 were globally sclerotic. The glomeruli had an unremarkable appearance, without mesangial expansion, mesangial hypercellularity, endocapillary hypercellularity, fibrinoid necrosis, karyorrhexis, or crescent formation. There was moderate interstitial fibrosis and tubular atrophy with a dense interstitial infiltrate of mixed interstitial inflammation, comprised of eosinophils, neutrophils, lymphocytes, plasma cells, and histiocytes within both intact and atrophic kidney parenchyma. There was patchy, but dense neutrophil-rich interstitial inflammation accompanied by neutrophilic rimming along the tubules and white blood cell casts (Figure 1). Both neutrophilic and lymphocytic tubulitis was identified. Immunofluorescence microscopy demonstrated strong linear IgG and C3 staining (3+ each) along the proximal tubular basement membranes without associated glomerular or distal tubular epithelial staining (Figure 2). IgG subclass staining revealed staining for all IgG subclasses along the TBMs (3+ each for IgG1, IgG2, IgG3, and IgG4). Electron microscopy did not reveal tubular basement membrane deposits.
This patient had a neutral urine except for urinary tract infection, especially when cultures grew E. coli. The CT scan of the abdomen and pelvis without contrast was suggestive of pyelonephritis, as it had stranding in the perinephric space (Figure 2). Serological studies for antinuclear antibodies, ANA, and antineutrophilic cytoplasmic antibodies, ANCA, were negative. Antiglomerular basement membrane antibodies were negative. Serologic testing for anti-TBM antibodies is not a routine clinical laboratory test, and therefore, was not tested initially. Even if this test was available and was positive, it is unclear whether there is an association between antibody titers and disease activity, as there is insufficient data available and no validated clinical assays.
The patient was initiated on intravenous methylprednisolone 40 mg every 8 hr but continued to require hemodialysis. A permcath was placed and the patient was eventually discharged home on prednisone 60 mg orally, daily, and continued intravenous Ceftriaxone 2 gram daily for an additional 2 weeks and scheduled for 3 times weekly hemodialysis.
After discontinuation of nivolumab, intravenous antibiotic therapy, and continued steroid therapy (prednisone 60 mg/day), and during that time, the patient was being supported by hemodialysis, the patient's kidney function gradually improved and prednisone dose was slowly tapered. The patient's renal function improved and hemodialysis was no longer required.
Serologic testing for anti-TBM antibodies by indirect immunofluorescence was performed and was negative, suggestive of serologic remission. The patient was 6 weeks of being on steroids, nivolumab discontinued, and intravenous antibiotics. Baseline titers were not available for comparison.