A 51-year-old Caucasian woman with an unremarkable medical history developed cloudy and subsequently brown-colored urine on 25th September 2021. The patient received ciprofloxacin treatment for a suspected urinary tract infection.
Subsequently, she developed oliguria, edema, resting dyspnea, vomiting, and diarrhea. In light of these emerging symptoms, she was admitted to a secondary care hospital. Initial laboratory evaluation showed anemia, high C-reactive protein (CRP) without procalcitonin (PCT) elevation, and mild leukocytosis (Fig. 1).
Urine dipstick testing found hematuria and proteinuria; automated sediment revealed leukocytes and erythrocytes but no bacteria. Arterial blood gas analysis showed mixed respiratory and metabolic acidosis. Blood and urine cultures were negative. Ultrasonographic findings showed bilateral renal enlargement and increased parenchymal echogenicity.
The suspected diagnosis was acute kidney injury due to possible septicemia; hence initial treatment with empirical intravenous amoxicillin/clavulanic acid was initiated. Nevertheless, soon she became anuric, and laboratory abnormalities also worsened, hence hemodialysis was commenced. At this point, the patient was transferred to a nephrology unit department for further evaluation.
Post-infectious glomerulonephritis, vasculitis, renal arterial or venous thrombosis was suspected as differential diagnoses. Due to the high CRP, empirical imipenem/cilastatin, and intravenous methylprednisolone (125 mg), were initiated. Anti-nuclear antibody screening test, anti-neutrophil cytoplasmic antibodies, and anti-streptolysin O serology were negative. Complement levels were normal. Hepatitis A, B, C, E, and HIV infections were ruled out. Thrombosis could not be proved either. Chest X-ray demonstrated pleural effusion and basilar pulmonary edema, which also was confirmed by non-enhanced chest CT.
In order to perform a renal biopsy, the patient was transferred to our nephrology division at the Department of Internal Medicine and Oncology.
Upon admission to our department, we could not reveal any nephrotoxic medication or substance use. Zoonotic infection was not probable. She lived a physically active lifestyle but did not exert herself beyond normal. Nonetheless, two weeks before her urinary discoloration, she had had an upper respiratory tract infection.
Laboratory findings on admission showed anemia, leukocytosis, and secondary hyperparathyreosis. Immunologic testing revealed circulating anti-GBM antibody level of 2822 CU, and anti-PLA2R titer of 1:320 (Fig. 1).
This rare serologic constellation prompted a renal biopsy. The total number of obtained glomeruli was 16, of which one was globally sclerosed, and 14 showed cellular crescent formation some with fibrinoid necrosis and capillary wall rupture. In some other glomeruli, Bowman’s capsule integrity was also disrupted. Advanced interstitial fibrosis/tubular atrophy could also be observed. Immunofluorescence microscopy demonstrated both linear and granular depositions of immunoglobulin G, kappa and lambda light chains, and C3. Staining with PLA2R appeared as granular signal. One non-crescentic glomerulus was available for electron microscopy that showed Ehrenreich-Churg III-IV stage subepithelial immunocomplex deposits (Fig. 2).
Based on the clinical and histological findings, the patient was diagnosed with anti-GBM glomerulonephritis and concomitant PLA2-R positive membranous nephropathy.
Based on these findings we initiated prompt plasmapheresis and induction therapy with intravenous methylprednisolone. From day three, she continued to receive pulse cyclophosphamide fortnightly.
During her inpatient stay, she underwent six plasmapheresis sessions and received in total of 4.5 g intravenous methylprednisolone, and 1250 mg cyclophosphamide. Steroid was continued and tapered orally. Subsequently, anti-GBM antibody titer decreased to 424 CU, and anti-PLA2R became negative. Despite all this aggressive treatment, her renal function did not improve, and she remained dialysis-dependent. At present living-donor kidney transplantation is planned after her immunological remission.