Acute interstitial nephritis associated with immune checkpoint inhibitors: a single-centre experience

Abstract

Background Checkpoint inhibitors (CPIs) are used to treat solid organ metastatic malignancies. They act by triggering a vigorous immune response against tumoural cells, preventing their proliferation and metastasis. However, this is not a selective response and can cause immune-related adverse events (irAEs). The kidney can potentially be damaged, with an incidence of irAEs of 1–4%. The most frequent type of toxicity described is acute interstitial nephritis (AIN). Methods We conducted a study of patients with solid organ metastatic malignancies treated with immunotherapy who developed acute renal injury and underwent kidney biopsy in the last 14 months at the Vall d’Hebron University Hospital. Results In all, 826 solid organ malignancies were treated with immunotherapy in our centre, 125 of them (15.1%) developed acute kidney injury (AKI), 23 (18.4% of AKI) visited the nephrology department and 8 underwent kidney biopsy. The most frequent malignancy was lung cancer, in five patients (62%), followed by two patients (25%) with melanoma and one patient (12%) with pancreatic cancer. Four patients (50%) had already received previous oncological therapy, and for the remaining four patients (50%), CPI was the first-line therapy. Five patients (62%) were treated with anti-programmed cell death protein 1, three patients (37%) received anti-programmed death ligand 1 and two (25%) patients were treated in combination with anti-cytotoxic T-lymphocyte antigen 4. The time between the start of CPI and the onset of the AKI ranged from 2 to 11 months. The most frequent urine findings were subnephrotic-range proteinuria, with a mean protein:creatinine ratio of 544 mg/g (standard deviation 147) and eosinophiluria. All patients were biopsied after being diagnosed with AIN. Three patients (37%) received treatment with pulses of methylprednisolone 250–500 mg/day and five patients (62%) received prednisone 1 mg/kg/day. Seven patients (87%) experienced recovery of kidney function and one patient (12%) progressed to chronic kidney disease. Conclusions We report on eight patients with CPI-related AIN diagnosed in the last 14 months at our centre. The novel immunotherapy treatment of metastatic solid organ malignancies carries a higher risk of irAEs. The kidney is one of the most commonly affected organs, frequently presenting as an AIN and exhibiting a favourable response to steroid treatment.

Biomarkers, Clinical Features, and Rechallenge for Immune Checkpoint Inhibitor Renal Immune-Related Adverse Events

“…As previously reported, subnephrotic proteinuria and pyuria were present in patients with ICI-AKI 26 , 27 and they had greater number of urinary white blood cells, red blood cells, and blood leucocyte count as compared with non–ICI-AKI. Hansel stain was not performed or was negative in most of the patients, as it is well known that its sensitivity/specificity is quite low for AIN diagnosis.…”

Checkpoint inhibitor therapy-associated acute kidney injury: time to move on to evidence-based recommendations

“…In a study published in this issue, Oleas et al [ 16 ] report a single-center study of patients with nonhematologic malignancies who received ICI treatment during a 14-month period, experienced AKI (based on the Acute Kidney Injury Network criteria) and underwent a kidney biopsy at the Vall d’Hebron University Hospital, Barcelona, Spain. During this period, 826 patients with nonhematologic organ malignancies received ICI treatment and AKI occurred in 125 patients (15.1%).…”

“…In this study, the median time from ICI initiation to AKI was 14 weeks (range 6–37) [ 18 ]. In this study, the time between the start of ICI and the onset of AKI was a mean of 5.8 months (range 2–11) [ 16 ]. In the study by Isik et al [ 17 ], AKI was found to develop earlier in the ICI-AKI patients compared with the non-ICI-AKI patients {median 4 months [95% condfidence interval (CI) 1.2–11.4] versus 8.5 months [95% CI 5.3–10.4], respectively; P = 0.026}.…”

“…Although corticosteroid treatment may not affect oncologic outcomes, they are still associated with an increased incidence of sepsis, venous thromboembolism and fractures in population-based cohort studies, even in patients with short and moderate corticosteroid exposure [ 23 ]. In the study by Oleas et al [ 16 ], three patients (37%) received treatment with pulses of methylprednisolone 250–500 mg/day and five patients (62%) received prednisone 1 mg/kg/day. Seven of eight patients (87%) experienced recovery of kidney function and one patient (12%) progressed to chronic kidney disease.…”

Renal tubular acidosis and acute kidney injury secondary to cemiplimab

“…This has been seen in about 2%-5% of the patients. [1][2][3][4]5 Less commonly, immune checkpoint inhibitors can lead to glomerulonephritis. 3,6,7 Renal tubular acidosis is a very rare presentation of immunerelated kidney side effects.…”