Immune-related ureteritis and cystitis induced by immune checkpoint inhibitors: Case report and literature review

Abstract

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) and anti-programmed death cell protein 1 (anti-PD-1), are increasingly prescribed in metastatic carcinoma therapy. ICI-related kidney injury is gradually recognized by clinicians. However, immune-related ureteritis and cystitis easily go undiagnosed. We report three cases of PD-1 monoclonal antibody (mAb)-related ureteritis and cystitis. We further carried out a review of the literature about ICI-related ureteritis and cystitis. The cases in our reports manifest urinary irritation, sterile pyuria, gross hematuria, hydronephrosis, dilation of the ureters, and acute kidney injury. Urinary irritation improved effectively; urinalysis and renal function returned to normal after glucocorticoid therapy. During ICI therapy, urinalysis and renal function and urinary imaging examination are recommended to be monitored regularly. It contributes to identify immune-related ureteritis/cystitis earlier to efficiently alleviate urinary symptoms and immunologic urinary tract injury through glucocorticoid therapy while avoiding the abuse of antibiotics.

A single-cell transcriptomic atlas characterizes molecular features in ureteritis/cystitis induced by immune checkpoint inhibitors

“…IrAEs usually affect epithelial tissues (including those of the skin, lung, and gut) because these environmental interfaces are prone to large in ltrations of tissue-resident memory T cells (1,24). In ltration of T cells into the urothelial barrier have been observed in ICI-induced ureteritis/cystitis (3)(4)(5)10). We considered two molecular mechanisms as opportunities for therapeutic intervention and the prevention of irAE: (1) the recruitment of T cells to epithelial tissues; and (2) T cell activation.…”

“…Histopathologic analysis has revealed the presence of CD8 + T cell expansions in multiple organs affected by ICI toxicity (1,4,10,18,29,30). Moreover, the expansion and activation of T cells also play a role in ICIinduced ureteritis/cystitis (3,4).…”

“…Histopathologic analysis has revealed the presence of CD8 + T cell expansions in multiple organs affected by ICI toxicity (1,4,10,18,29,30). Moreover, the expansion and activation of T cells also play a role in ICIinduced ureteritis/cystitis (3,4). The results of the present study were consistent with these ndings as our IHC analyses con rmed in ltrates of CD8 + lymphocytes in the bladder tissue of the ureteritis/cystitis patient but not in those of the control subject (Fig.…”

“…However, irAEs involving the urinary tract and bladder are rarely reported and often ignored by oncologists. To date, approximately ten cases with ICIinduced ureteritis/cystitis have been reported (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The symptoms of ICI-induced ureteritis/cystitis mainly include hematuria, pollakiuria, painful micturition, and sometimes acute kidney injury complications (4).…”

“…To date, approximately ten cases with ICIinduced ureteritis/cystitis have been reported (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The symptoms of ICI-induced ureteritis/cystitis mainly include hematuria, pollakiuria, painful micturition, and sometimes acute kidney injury complications (4). The diagnosis poses a challenge because the differential diagnoses of bacterial cystitis, metastasis, and radiation-or other drugs-induced cystitis have to be excluded.…”