Adjunctive pentoxifylline in refractory nephrotic-range proteinuria due to paraproteinemia

Persistent nephrotic-range proteinuria in cancer patients can compromise ongoing cancer therapy and prognosis. Although renin-angiotensin-aldosterone system (RAAS) blockade and sodium–glucose cotransporter 2 (SGLT2) inhibitors are mainstays of therapeutic management, proteinuria often persists. Patients who present with this clinical picture require a unique therapeutic approach. Pentoxifylline, a non-selective phosphodiesterase inhibitor with anti-inflammatory and anti-fibrotic properties, has shown proteinuria-lowering potential, but is not widely utilized in the United States for proteinuria management. We present a case of persistent proteinuria despite maximum-dose losartan and empagliflozin in a patient with AL amyloidosis and multiple myeloma not in remission. This patient demonstrated a reduction in proteinuria to modest levels (<1 g/g) following the addition of pentoxifylline 400 mg twice daily, allowing uninterrupted cancer treatment. Notably, there was an 86% decrease in urine protein/creatinine ratio (UPCR). This case illustrates the potential role of pentoxifylline as an adjunctive agent for refractory proteinuria in the onconephrology setting. Wider awareness and consideration of this inexpensive oral therapy may help optimize renal and oncologic outcomes in this vulnerable population.