scholarly journals Efficacy of Plasmapheresis in Nivolumab-Associated ANCA Glomerulonephritis: A Case Report and Pathophysiology Discussion

2021 ◽  
pp. 376-383
Author(s):  
Reda Laamech ◽  
Florian Terrec ◽  
Camille Emprou ◽  
Anne Claire Toffart ◽  
Thomas Pierret ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Exceptional Case ◽  
Solid Organ ◽  
Glomerular Injury ◽  
Cancer Treatments ◽  
Drug Induced ◽  
Hematologic Cancer ◽  
Lung Hemorrhage

Immune checkpoint inhibitors (ICIs) have revolutionized solid organ and hematologic cancer treatments by improving overall prognoses. However, they can lead to overactivation of the immune system and several immune-related adverse events and sometimes affecting the renal system. Although acute interstitial nephritis is well described, we know little about ICI-associated glomerular injury. Herein, we report an exceptional case of renal ANCA positive-associated vasculitis (AAV) after nivolumab therapy. Three weeks after the last nivolumab injection, the patient presented with proteinuria at 1.73 g/g of creatininuria, hematuria, and acute kidney injury needing dialysis associated with lung hemorrhage; anti-neutrophil cytoplasmic antibody (ANCA titer ≥1,280 with myeloperoxidase specificity of 780 U/mL) was positive, and kidney biopsy confirmed glomerular injury with crescents. The patient underwent treatment with steroid pulses, rituximab, and plasmapheresis, resulting in an improvement of the renal function and lung hemorrhage and produced a negative ANCA titer. Despite the results of the PEXIVAS study and the absence of clear benefit of plasmapheresis demonstrated in idiopathic AAV, we suggest that drug-induced AAV may be effectively treated by plasmapheresis, steroids, and rituximab.

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 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 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.

scholarly journals Development of Nivolumab/Ipilimumab-Associated Autoimmune Nephritis during Steroid Therapy

2021 ◽  
pp. 270-274
Author(s):  
Ellen Gebauer ◽  
Wibke Bechtel-Walz ◽  
Christoph Schell ◽  
Michelle Erbel ◽  
Gerd Walz ◽  
...  
Keyword(s):  
Steroid Therapy ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Oral Steroid ◽  
High Dose ◽  
Immune Mediated

Immunotherapy using immune checkpoint inhibitors revolutionized therapies for a variety of malignancies. Nivolumab, an antibody blocking programmed cell death 1 protein, and ipilimumab that blocks cytotoxic T-lymphocyte-associated protein 4 effectively target tumor cells by disinhibiting the endogenous immune response. At the same time, unrestrained T-cell activation may trigger a range of immune-mediated side effects including kidney injury. Steroid therapy constitutes the mainstay of treatment of these adverse events, but dosage, route of administration, and approach to nivolumab re-exposure remain unclear. Here, we report the case of a 72-year-old male patient who developed severe nivolumab/ipilimumab-associated acute kidney injury while on oral steroid therapy for immune-mediated colitis. Acute interstitial nephritis was confirmed by renal biopsy. Administration of high-dose intravenous steroid doses was required to revert declining renal function.

A case of immune-complex mediated glomerulonephritis associated with pembrolizumab

2021 ◽  
pp. 239936932110646
Author(s):  
Marco Bonilla ◽  
Vanesa Bijol ◽  
Antonio Gabriel De Leon Corona ◽  
Kevin M. Sullivan ◽  
Kenar D. Jhaveri
Keyword(s):  
Acute Kidney Injury ◽  
Immune Complex ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
High Dose ◽  
Dramatic Improvement ◽  
Pathologic Finding ◽  
Glomerular Injury ◽  
Metastatic Lung ◽  
Dose Prednisone

Introduction: Immune checkpoint inhibitors (ICI) are changing the way we treat cancer. However, these novel agents have various systemic adverse events that may preclude its use and cause poor patient outcomes. ICI-associated acute kidney injury is an emerging complication of this treatment. While tubulointerstitial disease is the most common pathologic finding of patients with ICI-associated AKI, there is sparse data in medical literature describing its association with glomerular disease. Case report: Here, we present a patient with metastatic lung adenocarcinoma who developed acute kidney injury and significant proteinuria after receiving pembrolizumab. The kidney biopsy revealed a membranoproliferative and diffuse segmental endocapillary proliferative pattern of glomerular injury. Management and outcome: Pembrolizumab was then held and high-dose prednisone was initiated, resulting in a rapid and dramatic improvement in kidney function and proteinuria. Discussion: We highlight a report of a patient diagnosed with immune-complex mediated glomerulonephritis associated with the use of pembrolizumab, who was successfully treated with drug withdrawal and corticosteroids.

scholarly journals Investigation of novel biomarkers of drug-induced kidney injury in renal transplant recipients undergoing graft biopsy

2019 ◽  
Author(s):  
Arthur Michon ◽  
Antoine Durrbach ◽  
Jean-Charles Gautier ◽  
Xavier Benain ◽  
Catherine Lunven ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Serum Creatinine ◽  
Diagnostic Performance ◽  
Kidney Injury ◽  
Renal Transplant Recipients ◽  
Urinary Ngal ◽  
Urinary Proteins ◽  
Glomerular Injury ◽  
Drug Induced ◽  
Neutrophil Gelatinase Associated Lipocalin

Abstract Urinary and blood kidney biomarkers (BM) remain insufficient to detect early kidney injury. Our aim was to compare new kidney BM with histopathological data in kidney allograft recipients. Blood and urine samples of consecutive adult patients were collected just prior graft biopsy. All kidney samples were classified according to Banff 2007. The diagnostic performance (area under ROC curve, AUROC) of 16 new BM was compared to those of urinary proteins, blood urea nitrogen, eGFR and serum creatinine to identify histopathological groups. 223 patients were analyzed. Versus slightly modified renal parenchyma (SMRP), microalbuminuria and urinary proteins had the highest diagnostic performance toward glomerular injury. Urinary neutrophil gelatinase associated lipocalin (NGAL) had the best performance values for acute tubular necrosis (ATN) versus SMRP (AUROC 0.93). Others BM reached slightly lower AUROC reaching 0.89. When comparing ATN to acute rejection several new urinary BM (NGAL, cystatin C, and MCP1) and classical BM (eGFR, serum creatinine) reached similar AUROC values ranging from 0.80 to 0.85. Values of urinary NGAL were 10-fold higher in ATN compared to acute rejection (p = 0.0004). New BM did not outperform classical BM during renal transplantation. Urinary NGAL might be helpful to discriminate ATN and acute rejection.

scholarly journals Traditional Renal Biomarkers and New Approaches to Diagnostics

2018 ◽  
Vol 46 (8) ◽  
pp. 999-1001 ◽  
Author(s):  
Mary B. Nabity
Keyword(s):  
Kidney Injury ◽  
Small Rna Sequencing ◽  
Successful Implementation ◽  
Preclinical Studies ◽  
Glomerular Injury ◽  
Drug Induced ◽  
Irreversible Damage ◽  
Urine Biomarkers ◽  
Renal Biomarkers ◽  
Highly Sensitive

Traditional biomarkers of renal disease have a number of limitations, whether evaluating veterinary patients or performing preclinical toxicity studies. Serum creatinine and urea nitrogen are affected by nonrenal influences that limit their usefulness for detecting small but significant decreases in glomerular filtration rate (GFR) in veterinary patients. These nonrenal influences can be more controlled in preclinical studies than in clinical patients; however, because of its high functional reserve, these estimates of GFR are insensitive for detecting kidney injury prior to loss of a substantial proportion of functioning nephrons. Urine biomarkers can be highly sensitive for tubular or glomerular injury that might lead to irreversible damage to the nephron. Several proteins are qualified by the Food and Drug Administration for nonclinical application as urinary biomarkers of drug-induced nephrotoxicity, and many of these also have preliminary data supporting their usefulness for kidney injury in dogs and cats. In addition to these relatively recently identified biomarkers, efforts are underway to discover new renal biomarkers using a variety of techniques including liquid chromatography–mass spectrometry and small RNA sequencing. Ultimately, the interplay between preclinical studies and clinical patients in discovery and validation of renal biomarkers is critical to their successful implementation.

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.

A case of relapsing immunoglobulin A nephropathy secondary to immunotherapy

2020 ◽  
Vol 4 (3) ◽  
pp. 87-91
Author(s):  
Omar Mamlouk ◽  
Biruh Workeneh
Keyword(s):  
Minimal Change Disease ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Immunoglobulin A ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Minimal Change ◽  
Immunoglobulin A Nephropathy ◽  
First Case ◽  
Immunosuppression Therapy

An estimated 3% of patients treated with immune checkpoint inhibitors develop acute kidney injury during the treatment course. The majority of biopsy-proven checkpoint inhibitor–associated nephropathy is related to acute interstitial nephritis, but various glomerulonephritides have been reported, including immunoglobulin A nephropathy and minimal change disease. Secondary immunoglobulin A nephropathy can be associated with autoimmune and infectious disease, but, unlike minimal change disease, rarely as a result of medications. To date, there are no clear evidences that treating secondary immunoglobulin A nephropathy or minimal change disease with immunosuppression therapy provides resolution for glomerulonephritis. We report the first case of remission of checkpoint inhibitor–induced overlap immunoglobulin A/minimal change disease nephropathy treated with repository corticotrophin therapy.

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