Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases

Abstract

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary “lupus-like” membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with “lupus-like” nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition.