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<p>Therapeutic monoclonal antibodies (mAbs) have revolutionized the treatment landscape of various diseases, offering targeted therapy options with high specificity. Under normal physiological conditions, their size prevents renal excretion. However, there is limited information about mAbs pharmacokinetics in patients with massive proteinuria, a condition often associated with a nephrotic syndrome. In this case report, we describe a 68-year-old man with non-small-cell lung carcinoma (NSCLC) and a paraneoplastic nephrotic syndrome, who was treated with pembrolizumab 200&#xa0;mg every 3&#xa0;weeks. Since there is limited data on pembrolizumab disposition in patients with nephrotic syndrome, we monitored pembrolizumab serum and urine concentrations to ensure adequate systemic exposure. Therapeutic drug monitoring results showed no renal excretion of pembrolizumab and therapeutic drug exposure. Treatment of the NSCLC led to an amelioration of the paraneoplastic nephrotic syndrome. We conducted a literature review on the various types of proteinuria and their effects on the excretion of mAbs. Existing literature shows that increased renal clearance of monoclonal antibodies in patients with glomerular proteinuria is possible, but it probably depends on the amount of glomerular proteinuria. Based on literature findings and our own, we suggest that in cases of severe glomerular proteinuria, like nephrotic range proteinuria, the likelihood of renal loss of monoclonal antibodies is higher than in other cases.</p>

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Proteinuria and influence on monoclonal antibody excretion: a pembrolizumab case report and literature review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月2日

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  • T. S. S. Teuntje van Es,
  • B. J. M. Bas Peters,
  • G. Gurbey Ocak,
  • E. A. Elisabeth Kastelijn,
  • S. L. Sabine Croonen,
  • F. C. Floris Loeff,
  • M. P. H. Marcel van den Broek

摘要

Therapeutic monoclonal antibodies (mAbs) have revolutionized the treatment landscape of various diseases, offering targeted therapy options with high specificity. Under normal physiological conditions, their size prevents renal excretion. However, there is limited information about mAbs pharmacokinetics in patients with massive proteinuria, a condition often associated with a nephrotic syndrome. In this case report, we describe a 68-year-old man with non-small-cell lung carcinoma (NSCLC) and a paraneoplastic nephrotic syndrome, who was treated with pembrolizumab 200 mg every 3 weeks. Since there is limited data on pembrolizumab disposition in patients with nephrotic syndrome, we monitored pembrolizumab serum and urine concentrations to ensure adequate systemic exposure. Therapeutic drug monitoring results showed no renal excretion of pembrolizumab and therapeutic drug exposure. Treatment of the NSCLC led to an amelioration of the paraneoplastic nephrotic syndrome. We conducted a literature review on the various types of proteinuria and their effects on the excretion of mAbs. Existing literature shows that increased renal clearance of monoclonal antibodies in patients with glomerular proteinuria is possible, but it probably depends on the amount of glomerular proteinuria. Based on literature findings and our own, we suggest that in cases of severe glomerular proteinuria, like nephrotic range proteinuria, the likelihood of renal loss of monoclonal antibodies is higher than in other cases.