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 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 Acute interstitial nephritis with immunotherapy; a growing entity?

2020 ◽  
Vol 9 (4) ◽  
pp. e35-e35
Author(s):  
John David Chetwood ◽  
Lin Lin Myat ◽  
Helen Lammi ◽  
Mani Panat ◽  
James Hughes
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Interstitial Nephritis ◽  
Cancer Survival ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Response To Treatment ◽  
Immune Mediated ◽  
Life Threatening ◽  
Potential Impact

We report a case of acute kidney injury (AKI) secondary to immune-mediated acute interstitial nephritis (AIN), with supporting diagnostic results and a successful response to treatment. This entity is gaining increasing recognition with the burgeoning use of immunotherapy agents in oncology. The timeline for the development of AIN from the initiation of immunotherapy varies, and may range in severity from asymptomatic to severe, organ-threatening and with life threatening consequences. Renal biopsy should be performed to confirm the diagnosis due to the potential impact of discontinuation of immunotherapy on cancer survival. Re-challenge with immunotherapy is reasonable once renal function recovers.

scholarly journals Acute interstitial nephritis due to sodium-glucose co-transporter 2 inhibitor empagliflozin

2020 ◽  
Author(s):  
Rebecca Ryan ◽  
Stephanie Choo ◽  
Jamie Willows ◽  
Julie Walker ◽  
Kolanu Prasad ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Interstitial Nephritis ◽  
Clinical Observation ◽  
Kidney Injury ◽  
Corticosteroid Treatment ◽  
Acute Interstitial Nephritis ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Randomized Controlled

Abstract Biopsy-proven acute interstitial nephritis (AIN) secondary to sodium-glucose co-transporter 2 (SGLT2) inhibitors has not been described previously. Here, we report on the management of a patient with severe acute kidney injury that developed 6 weeks after starting empagliflozin. The cause was confirmed as AIN on renal biopsy. Our patient recovered, without the need for dialysis, with discontinuation of empagliflozin and corticosteroid treatment. This novel clinical observation is likely to occur more frequently as these drugs are increasingly being prescribed, given that recent randomized controlled trials including EMPA-REG (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) showed SGLT2 inhibitors can decrease cardiovascular mortality, among other benefits, in high-risk diabetic populations.

scholarly journals Clinical Manifestations and Outcome of Fluoroquinolone Associated Acute Interstitial Nephritis

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S297-S297
Author(s):  
Saira Farid ◽  
Omar AbuSaleh ◽  
Maryam Mahmood ◽  
Zerelda Esquer Garrigos ◽  
Abdurrahman Hamadah ◽  
...  
Keyword(s):  
Renal Function ◽  
Interstitial Nephritis ◽  
Treatment Duration ◽  
Case Reports ◽  
Clinical Manifestations ◽  
Acute Interstitial Nephritis ◽  
Flank Pain ◽  
High Index Of Suspicion ◽  
Baseline Renal Function ◽  
Antibiotic Treatment Duration

Abstract Background Fluoroquinolones (FQ) are among the most commonly prescribed antibiotics. Nephrotoxicity related to FQ use is infrequently reported and the mechanism of renal injury is incompletely elucidated. We describe clinical manifestations and outcome of patients with biopsy proven acute interstitial nephritis (AIN) associated with FQ use at our institution. Methods We conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic Rochester from 1993 to 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy proven AIN that were attributed to FQ use. Results We identified 24 patients with FQ-related biopsy-proven AIN. The most commonly used FQ was ciprofloxacin (71%) with median antibiotic treatment duration of 7 days (Figure 1). The median duration between starting FQ and the diagnosis of AIN was 8.5 (IQR: 17). Common clinical manifestations included fever (50%), flank pain (8%), and skin rash (21%). However, 17% of the patients were asymptomatic at the time of diagnosis (Figure 2). Majority (58%) of the patients recovered following discontinuation of antibiotics and returned to baseline renal function at a median of 20.5 (IQR: 15.5). Six patients required temporary hemodialysis and 9 patients received steroids. Conclusion Onset of FQ-related AIN can be delayed and a high index of suspicion is needed by physicians prescribing these agents. Overall outcomes are favorable with recovery to baseline renal function within 3 weeks of discontinuing the offending drug. Disclosures All authors: No reported disclosures.

MO404ACUTE KIDNEY INJURY DUE TO IMMUNE CHECKPOINT INHIBITORS (CPIS) NEPHROTOXICITY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Fausta Catapano ◽  
Elisa Persici ◽  
Giulia Ubaldi ◽  
Francesca Romani ◽  
Elena Mancini
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Long Term Follow Up

Abstract Background and Aims The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding; however the immune-related toxicities associated with CPIs can limit its efficacy. Case Report. A 52 year-old female diagnosed with left ocular melanoma and treated for 14 months with nivolumab developed non-oliguric, stage 3 (KDIGO), Acute Kidney Injury (AKI) and mixed proteinuria (0.6 g/day), then was transferred in our Unit. As known causes of AKI were excluded, kidney biopsy was performed. By Optical Microscopy, there were 33 normal glomeruli; arteries and arterioles were normal. The main damage was interstitial and characterized by tubulitis, tubular necrosis, non-isometric citoplasmatic vacuolization and diffuse, acute and chronic, CD4+, inflammatory infiltrate (Figure 1, 2). By Immunofluorescence, 27 glomeruli were negative for all eight tested antibodies (IgA, IgM, IgG, F, C3, C1q, kappa and lambda light chains). On the basis of these histological findings, Nivolumab-induced Acute Tubulo-Interstitial Nephritis was diagnosed. Nivolumab was discontinuated. Patient was treated by steroids and she achieved almost complete renal function recovery (Figure 3). Conclusions. CPIs can induce a long-term Acute Kidney Injury. Histological features are characterized by Acute Tubulo-Interstitial Nephritis. Steroids can improve renal outcome. In patients treated with CPIs a multidisciplinary management between oncologists and nephrologists is desirable for monitoring renal function at basal, after drug administration and in the long-term follow-up.

P0573CLINICAL PRESENTATION AND OUTCOMES OF ACUTE INTERSTITIAL NEPHRITIS: A TEN YEARS' EXPERIENCE FROM A TERTIARY CARE HOSPITAL IN KARACHI, PAKISTAN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sonia Yaqub ◽  
Ayesha Aziz Rehman ◽  
Safia Awan
Keyword(s):  
Renal Function ◽  
Interstitial Nephritis ◽  
Initial Period ◽  
Tertiary Care ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Acute Interstitial Nephritis ◽  
Care Hospital ◽  
Steroid Use ◽  
Baseline Creatinine

Abstract Background and Aims Acute interstitial nephritis (AIN) is a potentially reversible, but relatively under-diagnosed cause of acute kidney injury. The effectiveness of steroids for treatment of AIN is debated. Data is scarce regarding the clinical presentation, use of steroids and its impacts on outcomes in AIN in our part of the world. The objective of our study was to study the clinical features, causes and outcomes of AIN and to evaluate the role of steroids in the management. Method We performed a retrospective study of 48 patients with biopsy proven AIN. Exposure was defined as the use of steroids. The main outcomes were recovery of renal function (Early (≤3 weeks) or Late (>3 weeks)) and hemodialysis dependence at 12 weeks Results 48 (4.9%) AIN cases were found among 978 renal biopsies performed from 2007-2018. Mean age was 47.6 ± 12.1 years. 56.3% were males. The offending agent was identified in 45.8% cases with NSAIDs (45.4%) being the most common, followed by antibiotics (22.7%), diuretics (9%), and PPI (4.5%). 75% presented with eGFR <15 ml/min/1.73m2 (n=36) out of which 58.3 % (n=21) needed hemodialysis. Mean proteinuria was 2.28 ± 0.99 g/day. 81.3% (n=39) patients received steroids out of which 39.6% were started on steroids after an initial period of observation after stopping the offending agent. Mean dose of prednisone was 0.8 ± 0.2 mg/kg per day. Mean time to steroid commencement was 14 ± 17.39 days. Early use of steroids (≤11 days after presentation) was significantly associated with earlier recovery (p= 0.009) as compared to late steroids (>11 days). A non-significant trend towards complete recovery (within 25% of baseline Creatinine) was noted in early steroid group (52.9%, n=17) vs “no steroid” (33.3%, n=9) or “late steroids” (10.5%, n=19) groups (p=0.208). 47.4% remained dialysis dependent on follow up with no difference made by steroid use (p=0.971). Conclusion Our data showed the benefit of earlier use of steroids in achieving rapid and complete renal recovery. Late steroid use was not associated with any further recovery of renal function at an additional risk of exposing patients to undue adverse effects. This is the first report from Pakistan documenting the tendency of nephrologists towards use of steroids for AIN.

scholarly journals Nilotinib-Induced Acute Interstitial Nephritis during the Treatment of Chronic Myeloid Leukemia

2021 ◽  
Vol 36 (2) ◽  
pp. 153-160.
Author(s):  
Min Jeong Kim
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Interstitial Nephritis ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
History Of

Tyrosine kinase inhibitors (TKIs) are targeted therapy drugs that selectively inhibit protein kinases. Nephrotoxicity associated with TKIs is uncommon. We report a case of a 39-year-old man with acute kidney injury that developed after nilotinib treatment for chronic myeloid leukemia (CML). The renal function of the patient decreased during treatment with nilotinib but improved when treatment was discontinued due to neutropenia. However, the renal function of the patient deteriorated again with the reintroduction of nilotinib for treatment. A renal biopsy revealed acute interstitial nephritis (AIN). The patient had no history of comorbidities and medication causing renal injury. Finally, we diagnosed the patient with nilotinib-induced AIN. After switching to imatinib mesylate, the renal function of the patient stabilized without further deterioration. Our case indicates that nilotinib can be a potential cause of renal dysfunction by inducing AIN when renal function deteriorates in patients treated with nilotinib.

Acute interstitial nephritis

2020 ◽  
pp. 4951-4956
Author(s):  
Simon D. Roger
Keyword(s):  
Renal Function ◽  
Interstitial Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Sudden Onset ◽  
Rapid Decline ◽  
Drug Induced ◽  
Chronic Renal Impairment ◽  
Loin Pain

Acute interstitial nephritis (AIN) is an inflammation of the tubules and interstitium within the kidney, associated with a relatively sudden onset and rapid decline in renal function. It is usually secondary to drugs (antibiotics, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors being most commonly incriminated), with other causes being infections (classically streptococcal, but this is now less common) and immune disorders (systemic lupus erythematosus, sarcoidosis, and tubulointerstitial nephritis with uveitis). Clinical features—the diagnosis of AIN should be considered in any patient with unexplained acute kidney injury. Drug-induced AIN may present with a classic allergic response, including arthralgias, fever, rash, loin pain, and eosinophilia/eosinophiluria, but these are not invariable and their absence does not exclude the diagnosis. The urine typically shows low-grade proteinuria (<1 g/day). Renal biopsy is the only way to confirm or exclude the diagnosis. Management and prognosis—treatment is by ceasing the offending agent, treating the concurrent infectious cause, or managing the immune aetiology with steroids (typically prednisolone 1 mg/kg per day, tapered to zero over 6–8 weeks). Most patients with drug-induced AIN recover renal function, but some are left with chronic renal impairment and a small proportion progress to endstage chronic kidney disease.

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 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.

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