Acute interstitial nephritis and PR3-ANCA following reintroduction of pembrolizumab: a case report

Immunotherapy ◽  
2021 ◽  
Author(s):  
Matthew Mulroy ◽  
Sanaz Ghafouri ◽  
Anthony Sisk ◽  
Antoni Ribas ◽  
Ray Goshtaseb ◽  
...  
Keyword(s):  
Interstitial Nephritis ◽  
Renal Toxicity ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Acute Interstitial Nephritis ◽  
Patients With Cancer ◽  
Previously Treated ◽  
Grade 3 ◽  
Timing Of Onset

Renal toxicity from immune checkpoint inhibitors (ICIs) is an increasingly recognized cause of acute kidney injury among patients with cancer. ICI-associated acute kidney injuries typically present as acute interstitial nephritis and the timing of onset is highly variable. Herein, we present a case of a patient with relapsed metastatic melanoma previously treated with pembrolizumab who developed grade 3 immune-related renal toxicity after reintroduction of the same ICI, secondary to acute interstitial nephritis with accompanying high PR3-antineutrophil cytoplasmic antibody titer. The patient improved after steroid treatment and discontinuation of pembrolizumab. This case highlights the importance of not excluding ICI-related nephrotoxicity as a possible cause of renal failure, including in those who previously tolerated ICI treatment, since it is a treatable entity.

scholarly journals A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation

2019 ◽  
Vol 13 (1) ◽  
pp. 42-45
Author(s):  
Xavier Charmetant ◽  
Cécile Teuma ◽  
Jennifer Lake ◽  
Frédérique Dijoud ◽  
Vincent Frochot ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Renal Toxicity ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Tubular Dysfunction ◽  
Distal Tubular Acidosis

Abstract The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.

scholarly journals Acute Interstitial Nephritis With Karyomegalic Epithelial Cells After Nivolumab Treatment—Two Case Reports

2019 ◽  
Vol 12 ◽  
pp. 117954761985364 ◽  
Author(s):  
Masaki Ryuzaki ◽  
Hirobumi Tokuyama ◽  
Kiyotaka Uchiyama ◽  
Hideaki Nakaya ◽  
Kazuhiro Hasegawa ◽  
...  
Keyword(s):  
Renal Function ◽  
Epithelial Cells ◽  
Interstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Kidney Injury ◽  
Corticosteroid Treatment ◽  
Acute Interstitial Nephritis ◽  
Tubular Epithelial Cells ◽  
Ki 67

Clinical application of immune checkpoint inhibitors (CPIs) including nivolumab is expanding in the field of oncology treatment. Nivolumab is an anti-programmed death 1 protein (PD-1) antibody designed to augment an immunologic reaction against cancer cells. On the contrary, CPIs are known to cause a unique variety of side effects termed as immune-related adverse events, which can affect any organ including kidney. However, the characteristics of renal disorders by nivolumab treatment are poorly described. We describe two cases of acute kidney injury that were treated with nivolumab. Two patients, one with renal-cell carcinoma and the other with lung cancer, exhibited progressive renal dysfunction after the initiation of nivolumab treatment. By kidney biopsy, each case was diagnosed as acute interstitial nephritis (AIN). Of note, tubular epithelial cells enlarged with hyperchromatic nuclei were focally observed, and this finding was consistent with karyomegalic tubular epithelial cells. In immunostaining, most of the enlarged tubular epithelial cells were positive for Ki-67, which suggested regeneration of tubular epithelial cells. Clinically, in one case, renal function was partially recovered with the discontinuation of nivolumab, while in another case renal function was fully recovered with additional corticosteroid treatment. We presented nivolumab-induced AIN with karyomegalic changes of tubular epithelia. We propose that immunosuppressive therapy may be necessary for the full recovery from renal impairment.

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

2020 ◽  
Author(s):  
Diana Oleas ◽  
Mónica Bolufer ◽  
Irene Agraz ◽  
Enriqueta Felip ◽  
Eva Muñoz ◽  
...  
Keyword(s):  
Interstitial Nephritis ◽  
Kidney Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
University Hospital ◽  
Solid Organ ◽  
First Line Therapy ◽  
Proliferation And Metastasis

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.

scholarly journals Acute interstitial nephritis and drug-induced systemic lupus erythematosus due to chlorthalidone and amiodarone: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2091002 ◽  
Author(s):  
Umut Selamet ◽  
Ramy M Hanna ◽  
Anthony Sisk ◽  
Lama Abdelnour ◽  
Lena Ghobry ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Interstitial Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Systemic Lupus ◽  
Drug Induced ◽  
Systemic Manifestations

Drug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s). Acute interstitial nephritis occurs due to DNA–drug or protein–drug complexes that trigger an allergic immune response. We report a patient who developed acute kidney injury, rash, and drug-induced systemic lupus diagnosed by serologies after starting chlorthalidone and amiodarone. A renal biopsy showed acute interstitial nephritis and not lupus-induced glomerulonephritis. It is important to note that systemic lupus erythematosus and acute interstitial nephritis can occur together, and this report highlights the role of the kidney biopsy in ascertaining the pathological diagnosis and outlining therapy in drug-induced lupus erythematosus.

scholarly journals The mechanisms of acute interstitial nephritis in the era of immune checkpoint inhibitors in melanoma

2019 ◽  
Vol 11 ◽  
pp. 175883591987554 ◽  
Author(s):  
Marco Tucci ◽  
Anna Passarelli ◽  
Annalisa Todisco ◽  
Francesco Mannavola ◽  
Luigia Stefania Stucci ◽  
...  
Keyword(s):  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acute Interstitial Nephritis ◽  
Clinical State ◽  
High Dose ◽  
Systemic Symptoms ◽  
The Impact

Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of patients with a number of types of cancer, but the frequent development of immune-related adverse effects (irAEs) can worsen the outcome. The most common irAEs involve the gastrointestinal, cutaneous, and endocrine systems, but nephrotoxicity, resulting from damage to the tubule-interstitial compartment, may occur in some patients. The early phases of acute interstitial nephritis (AIN) are characterized by systemic symptoms that indicate a poor clinical state as well as a mild deterioration of renal function. Tubular injury is due to a direct effect mediated by cytotoxic CD8+ T cells, which sustain the local production of pro-inflammatory cytokines that progressively impair renal function. The treatment of AIN is mainly based on high-dose steroids, which in most instances leads to the recovery of renal function. However, the premature discontinuation of ICI therapy may prevent the impact of treatment on the clinical progression of the malignancy. Adequately addressing irAEs requires a standardized therapy that is based on the results of large clinical trials.

scholarly journals Rifampicin Induced Acute Interstitial Nephritis in a Patient with Tubercular Lymphadenitis: A Case Report

2018 ◽  
Vol 8 (3) ◽  
pp. 257-259
Author(s):  
Hafsa Hassan Khan ◽  
Muhammad Abdur Rahim ◽  
Mehruba Alam Ananna ◽  
Tufayel Ahmed Chowdhury ◽  
Sarwar Iqbal
Keyword(s):  
Acute Kidney Injury ◽  
Case Report ◽  
Adverse Effects ◽  
Interstitial Nephritis ◽  
Case History ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
History Of ◽  
Tubercular Lymphadenitis ◽  
Prompt Diagnosis

Rifampicin is one of the most effective anti-tubercular agents. Among its rare adverse effects, acute interstitial nephritis (AIN) is noteworthy. Here, we describe the case history of a 55-year-old female with tubercular lymphadenitis who developed rifampicin induced AIN upon re-exposure and recovered satisfactorily without requiring steroids. Rifampicin induced AIN should be kept in mind when patients present with acute kidney injury as prompt diagnosis and discontinuation of the drug has excellent prognosis.Birdem Med J 2018; 8(3): 257-259

scholarly journals Time to Acute Kidney Injury in β-Lactam−Induced Acute Interstitial Nephritis

2020 ◽  
Vol 5 (7) ◽  
pp. 1068-1070 ◽  
Author(s):  
Benjamin Lazarus ◽  
Matthew R.P. Davies ◽  
Jason A. Trubiano ◽  
Rebecca Pellicano
Keyword(s):  
Acute Kidney Injury ◽  
Interstitial Nephritis ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis

Immune-related adverse events associated with immune checkpoint inhibitors in patients with cancer

2020 ◽  
pp. 030089162095346
Author(s):  
Nilay Sengul Samanci ◽  
Duygu Ilke Cikman ◽  
Kerem Oruc ◽  
Sahin Bedir ◽  
Emir Çelik ◽  
...  
Keyword(s):  
Adverse Events ◽  
Health Care Providers ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Care Providers ◽  
Patients With Cancer ◽  
Combination Treatments ◽  
Grade 3

Introduction: With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs. Methods: Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes. Results: A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti–programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti–programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments. Conclusion: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.

scholarly journals P0306ACUTE KIDNEY INJURY AFTER CHECKPOINT INHIBITOR TREATMENT: FACING THE FUTURE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Clara Garcã­a Carro ◽  
Mónica Bolufer ◽  
Diana Oleas ◽  
María A Azancot ◽  
Irene Agraz ◽  
...  
Keyword(s):  
Kidney Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Acute Interstitial Nephritis ◽  
University Hospital ◽  
Induction Treatment ◽  
Renal Lesion ◽  
Solid Organ

Abstract Background and Aims Checkpoint inhibitors (CPI) are used to treat solid organ metastatic malignancies. They act on by triggering a vigorous immune response against tumoral cells, preventing their proliferation. CPIs reinvigorate antitumor immune responses by interrupting co-inhibitory signaling pathways and promote immune-mediated elimination of tumor cells.This is not a selective response, deriving in immune related adverse events (irAEs). The kidney can potentially be damaged with an incidence of 13-29%. The most frequent type of toxicity is acute interstitial nephritis (AIN). Method We evaluated all the patients with solid organ metastatic malignancies treated with immunotherapy that developed acute renal injury (AKI) and underwent to kidney biopsy from March 2018 to November 2019 at Vall d’Hebron University Hospital. Results 11 patients with solid organ metastatic malignancies treated with immunotherapy developed AKI and underwent to kidney biopsy during the study period. The most frequent malignancy was lung cancer - in 6 patients-, followed by 3 patients with melanoma. 8 patients (72%) had already received previous oncological therapy, and for the remaining 3 patients (27%), CPI was the first line therapy. 8 patients (72%) were treated with anti-PD1 (programmed cell death protein 1), 4 patients (36 %) received anti PDL-1 (programmed death-ligand 1) 1 of these patients in combination with an anti CTLA-4 (cytotoxic T-lymphocyte antigen 4) and another patient received both anti PD1 and anti PDL-1. The time between the start of CPI and the onset of the AKI ranged between 2-11 months. The most frequent urine findings were subnephrotic range proteinuria with a mean protein/creatinine (mg/g creatinine) 503.6 ± 190.5 and leukocyturia in 9 of 11 patients. Mean creatinine (mg/dl) at diagnosis was 3.4 ± 1.3. 10 out of the 11 patients were diagnosed of AIN after performing a kidney biopsy. The remaining patient presented chronic changes (IFTA and glomerulosclerosis) in the biopsy, performed after receiving steroids for a month. 3 patients who presented AIN received pulses of methylprednisolone 250-500mg as induction treatment and 7 patients received prednisone 1mg/kg/day. Mean prednisone accumulated dose (mg) during the first month of treatment was 1387.5 ± 540. 9 patients experienced complete recovery of kidney function and two patients progressed to CKD. Conclusion We reported 11 patients who presented AKI associated to CPI treatment and underwent to kidney biopsy in the last 20 months at our center. 10 out of 11 presented biopsy confirmed CPI related AIN. In our experience, CPI related AIN is the most frequent renal lesion associated to the novel immunotherapy treatments. This entity seems to have good renal prognosis as long as steroid treatment is early started.

scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

Sign in / Sign up

Export Citation Format

Share Document