Anti-Glomerular Basement Membrane Disease in Association with Pembrolizumab Treated with Rituximab in Addition to...

Immune checkpoint inhibitors have significantly improved the prognosis of patients with certain malignancies; however, they can also be associated with diverse autoimmune organ toxicities, including those affecting the kidney.

A 75-year-old man was referred to the nephrology team with a progressive decline in kidney function over a 3-month period. His medical history included a diagnosis of non-small cell lung cancer for which he had been treated with pembrolizumab immunotherapy for the past 18 months (15 cycles). At referral, serum creatinine had risen from a baseline of 140 µmol/L to 208 µmol/L. Urinalysis showed blood and protein, and his urine protein creatinine ratio was 457 mg/mmol. An autoimmune screen yielded a positive anti-glomerular basement membrane (anti-GBM) antibody result (23 IU/L, normal range <7). He underwent a kidney biopsy. Light microscopy demonstrated focal and necrotising crescentic glomerulonephritis and eosinophilic tubulointerstitial nephritis. Immunofluorescence revealed linear IgG deposition along glomerular basement membranes. The patient did not have any clinical or radiographic evidence of pulmonary haemorrhage. A diagnosis of anti-GBM glomerulonephritis was made, and the patient received treatment with corticosteroids, seven cycles of plasma exchange, oral cyclophosphamide (total dose 3.3 g) and two intravenous doses of 1 g rituximab. The patient achieved a negative anti-GBM status within 1 week of presentation. Despite treatment for anti-GBM disease and cessation of pembrolizumab, his kidney function continued to decline, and his cancer progressed. Six months after diagnosis, he presented unwell to the hospital and received treatment for a presumed chest infection. Unfortunately, his condition deteriorated during this inpatient stay, and he passed away peacefully (6.7 months after induction treatment).

This case demonstrates a rare but important diagnosis of anti-GBM disease during pembrolizumab therapy. It highlights the challenges of managing immunosuppression and chemotherapy options in patients who are frail and with impaired kidney function.