Lesson for the clinical nephrologist: thrombospondin type-1 domain-containing protein 7A-associated membranous nephropathy and Fanconi syndrome in a patient with a squamous cell lung cancer

Excerpt

A 58-year-old male with a previous history of hypertension, type 2 diabetes and obesity was referred to our renal department with acute onset nephrotic syndrome and impaired kidney function. Four years prior to this presentation, kidney function was normal (estimated glomerular filtration rate [eGFR] Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 103 ml/min/1.73 m²) without known proteinuria. He was concurrently referred to the pulmonology department for the work-up of a suspicious lung lesion. Initial clinical and laboratory examination revealed peripheral edema, blood pressure 149/91 mmHg, eGFR 30 ml/min/1.73 m², serum albumin 6.8 g/l and proteinuria of about 23 g per day; anti-phospholipase A2 receptor 1 antibodies were negative. Kidney biopsy revealed minimal glomerular changes in the form of focal spikes seen in Jones Silver stain and faint deposition of IgG and C3 in a granular fashion along the glomerular basement membrane. Transmission electron microscopy showed subepithelial immune complex deposits compatible with membranous nephropathy (MN). The tubulointerstitial compartment was unremarkable except for mild interstitial fibrosis and tubular atrophy (10–15%) (Fig. 1). At the same time, squamous cell cancer of the left lung with mediastinal infiltration and lymph node metastases was diagnosed. Neoadjuvant chemotherapy with Carboplatin and Paclitaxel was initiated 1 week after diagnosis, and resection of the left upper lobe, mediastinal pleura and lymph node dissection was carried out after 4 months. Supportive therapy for nephrotic syndrome using RAAS blockade, diuretics, and therapeutic anticoagulation was also established. Despite curative treatment of the lung cancer, severe nephrotic syndrome persisted 7 months after the diagnosis, and the diagnostic work-up was extended by measuring anti-thrombospondin type 1 domain-containing protein 7A (THSD7A) antibody in the preserved and current sera. Antibody titer was > 1:1000 in the serum of the initial presentation and 1:100 in the serum two months after the completion of anti-cancer therapy. We also detected THSD7A in the tissues of lung cancer specimen, lymph nodes and glomeruli by immunohistochemistry (Fig. 1). Six months after the anti-cancer therapy, the patient received two courses of rituximab at a dose of 1 g on days 1 and 15 due to severe nephrotic syndrome, deteriorating kidney function and persistent anti-THSD7A antibodies. Six months after rituximab treatment, anti-THSD7A antibody was not detectable. During further follow-up, nephrotic syndrome and kidney function improved and anti-THSD7A antibody remained below detection level (Fig. 2).

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