Drug-induced Acute Interstitial Nephritis Research Articles

A Unique Case of Benralizumab Treatment for Drug-Induced Acute Interstitial Nephritis

A Unique Case of Benralizumab Treatment for Drug-Induced Acute Interstitial Nephritis

#1347 Development and validation of a nomogram for predicting complete kidney function recovery after drug-induced acute interstitial nephritis

Abstract Background and Aims Drug-induced acute interstitial nephritis (DI-AIN) represents a common cause of acute kidney injury. Early withdrawal of the culprit drug along with corticosteroid therapy (CS) remains the mainstay of treatment. Despite this, up to 50% of patients may not fully recover kidney function after DI-AIN. The aims of this study were to develop and externally validate a predictive nomogram to assess the probability of complete recovery (CR) of kidney function at 6 months after treatment. Method Multicenter, retrospective, observational study in 13 nephrology departments belonging to the GLOSEN group. Patients with biopsy proven DI-AIN treated with CS between 1996-2023 were included. Other potential causes of AIN such as infections or systemic diseases were carefully ruled out. Dataset was randomly divided into training group (n = 164) and validation group (n = 60). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of CR (serum creatinine value <25% of the last value before DI-AIN), and used to build the nomogram. Accuracy of the nomogram was assessed by discrimination and risk calibration, in the training and validation sets. Results The study group comprised 224 patients with DI-AIN, of whom: 51 (31%) in the training group and 19 (32%) in the validation set, achieved CR at 6 months after treatment with CS. Median age was 70 (IQR 57–76), and 115 (51%) were males. The clinical characteristics were well balanced between the training and validation data sets. The selected variables by LASSO were age (under/above 65 years), gender, degree of interstitial fibrosis and time to CS initiation (under/above 7 days). Based on multivariable logistic regression model, a nomogram was developed for assessing the probability of CR (Fig. 1). The area under the curve (AUC) of the nomogram was 0.809 (95% CI 0.721–0.880) indicating a good discriminative power. Bootstrap self- sampling was performed 1000 times for validation of the nomogram model. The AUC was 0.837 (95 % CI: 0.705–0.931), indicating good predictive stability. Calibration plot revealed that the predicted outcomes aligned well with the observations. Decision curve analysis (DCA), and clinical impact curve analysis (CICA) suggested that the model had clinical benefit. Conclusion We constructed and validated a practical nomogram with good discrimination and calibration, to predict the probability of CR of kidney function at 6 months in DI-AIN treated with corticosteroids. This clinical tool can provide clinicians with an estimate of kidney prognosis and can potentially assist them in titrating the intensity and duration of corticosteroid therapy.

WCN24-1040 Drug-Induced Acute Interstitial Nephritis

WCN24-1040 Drug-Induced Acute Interstitial Nephritis

23 Navigating Drug-Induced Acute Interstitial Nephritis and Renal Papillary Necrosis in a Renal Transplant Recipient

23 Navigating Drug-Induced Acute Interstitial Nephritis and Renal Papillary Necrosis in a Renal Transplant Recipient

A rare case of alirocumab (PCSK9 inhibitor)-associated acute interstitial nephritis.

Acute interstitial nephritis (AIN) is a common cause of hospital-acquired acute kidney injury (AKI) [1]. The most common cause of AIN is drug-induced AIN, which accounts for 60 - 70% of cases [2]. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9 inhibitor) is a monoclonal antibody that lowers low-density lipoprotein-C levels by inhibiting the PCSK9 protein [3]. Common adverse events reported with alirocumab include injection-site reactions, myalgia, neurocognitive disorders, and ophthalmologic disorders [4]. There is paucity of data, with few reported cases of AKI, mostly in the form of acute tubular necrosis (ATN) associated with alirocumab [5]. In this article, we present a novel case of AIN associated with the use of alirocumab.

#5781 DRUG-INDUCED ACUTE INTERSTITIAL NEPHRITIS (D-AIN): HOW TO IDENTIFY THE RESPONSIBLE DRUG?

Abstract Background and Aims The mainstay of D-AIN treatment is the removal of the responsible drug. However, it is not always easy to identify the culprit drug as this entity mainly affects elderly patients on multiple medications, they rarely associate systemic symptoms (rash, fever), and the timeline regarding the diagnosis and the associated drug is not always clear. Therefore, the diagnosis and treatment are delayed, making full renal function recovery less likely. The lymphocyte transformation test (LTT) has demonstrated to be useful in the identification of the involved drug in other hypersensitivity-mediated lymphocyte T diseases such as Stevens-Johnson Syndrome or Dress Syndrome. For this reason, we wonder if this test could be relevant in identifying the responsible drug in D-AIN. The aim of this study is to test LTT in patients with clinical and histological diagnosis of D-AIN. Method We have conducted a retrospective observational study in which we have collected data from 2019 to 2022 from our electronic databases. Results: We have registered 9 cases of D-AIN diagnosed with histological confirmation in whom the LTT had been performed. 22.2% of these patients were men. The mean age was 48.1 years (standard deviation of 15.8). None of them had previous chronic kidney disease (CKD). Mean peak creatinine at diagnosis was 4.66 mg/dl (standard deviation of 1.95). Regarding the typical symptoms of the D-AIN, three patients (33%) presented with fever and none of them suffered from rash. 6 patients had sterile pyuria (66%). All of them received steroid treatment. Concerning the LTT results, 7 cases were positive for one of the drugs the patient was taking, and 2 were negative. Among the positive cases, the identified drugs were 1 case of beta lactams (piperacillin), 1 case of PPIs (omeprazole), 1 case of metamizole, 1 case of paracetamol, 1 case of eslicarbazepine and 2 cases of NSAIDs (dexketoprofen), while the negative cases have not been suspected of taking any culprit drug. Conclusion LTT may be a useful test to identify the responsible drug for D-AIN, especially in patients taking multiple medications in which may be included some of great importance like immunotherapy (typical cause of D-AIN) in oncological treatments. In negative cases, it could be expected that the patient had taken medications difficult to be identified in the clinical history or, in some situations, the drug hapten responsible for kidney damage might be a drug metabolite and not the drug itself, which cannot be detected by the test.

Drug-Induced Acute Interstitial Nephritis with Surprise Final: A Concealed Suicide

Drug-Induced Acute Interstitial Nephritis with Surprise Final: A Concealed Suicide

Renal infiltration of peripheral T-cell lymphoma, not otherwise specified, mimicking drug-induced acute interstitial nephritis.

Renal invasion of T-cell lymphoma does not usually occur. The renal infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is rare. Therefore, the detailed pathology, clinical features, and effective therapy of this type of extranodal disease remain uncovered. Here, we report the rare case of acute kidney injury (AKI) caused by the renal infiltration of PTCL-NOS with no evidence of lymphadenopathy and extranodal lesions, except for the kidney. We mistakenly diagnosed our patient with drug-induced acute interstitial nephritis (AIN) at first, because his clinical features were similar to those of drug-induced AIN; however, we reached the correct diagnosis by detecting atypical T-cells in his urine. After the introduction of cyclophosphamide, doxorubicin, vincristine, and prednisone therapy his general condition improved rapidly. When suspecting drug-induced AIN as the cause of AKI, PTCL-NOS should also be recognized as one of the causes, and urine cytology may be useful to noninvasively distinguish between the two diseases.

Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: CON.

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0006642021 and the COMMENTARY: 10.34067/KID.0008342021

Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: PRO.

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007042021 and COMMENTARY: 10.34067/KID.0008342021

159 Diagnostic overlap of drug-induced acute interstitial nephritis with cutaneous involvement and drug-induced hypersensitivity syndrome

A common clinical dilemma is distinguishing maculopapular exanthem (MPE) with systemic symptoms from severe cutaneous drug reactions, such as drug-induced hypersensitivity syndrome (DIHS). Drug-induced acute interstitial nephritis (DI-AIN) with MPE can be especially challenging to differentiate from DIHS with renal involvement. It is crucial to distinguish DI-AIN from DIHS as the prognosis and treatment differ. Our goal was to estimate the percentage of published DI-AIN cases meeting RegiSCAR criteria for DIHS and characterize the outcomes.

Vonoprazan-associated nephrotoxicity: extensive real-world evidence from spontaneous adverse drug reaction reports

Vonoprazan-associated nephrotoxicity: extensive real-world evidence from spontaneous adverse drug reaction reports

AIN and role of steroids

BACKGROUND:
 Acute interstitial nephritis (AIN) is a potentially reversible, but under-diagnosed cause of acute kidney injury. The role of steroids in the management of drug-induced AIN is debatable. There is scarcity of data on clinical characteristics of drug induced AIN, and role of steroids and its impact on renal outcomes from the developing countries.
 METHODS:
 We performed a retrospective study of patients with biopsy proven AIN over a period of 11 years. The main outcomes were recovery of renal function (Early (≤3 weeks) or Late (>3 weeks) and hemodialysis (HD) dependence at 12 weeks.

Clinicopathological Characteristics of Drug-Induced Acute Interstitial Nephritis and Role of Steroids in Management: A Single-Center Observational Study

Background: Acute interstitial nephritis (AIN) is a potentially reversible, but underdiagnosed cause of acute kidney injury. The role of steroids in the management of drug-induced AIN is debatable. There is scarcity of data on clinical characteristics of drug-induced AIN, management approach and effect of steroids on renal outcomes from the low-middle-income countries. Methods: We performed a retrospective study of patients with biopsy-proven AIN over a period of 12 years. The main outcomes were recovery of renal function (early (? 3 weeks) or late (> 3 weeks)) and hemodialysis (HD) dependence at 12 weeks. Results: A total of 48 (4.9%) AIN cases were found among 978 renal biopsies. Mean age was 47.6 ± 12.1 years and 56.3% were males. The offending agent could be identified in half of the patients (non-steroidal anti-inflammatory drugs (NSAIDs) most commonly followed by antibiotics, diuretics and proton pump inhibitor (PPI)). Three quarters of patients presented with estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 (n = 36), out of which 58.3% (n = 21) required HD. Thirty-nine (81.3%) patients ended up receiving steroids. Mean dose of prednisone was 0.8 ± 0.2 mg/kg per day. Early use of steroids (? 11 days) was significantly associated with earlier (? 21 days) onset of recovery (P = 0.003) as compared to late use of steroids (> 11 days). Conclusion: Our data showed the benefit of earlier use of steroids in achieving rapid and complete renal recovery in drug-induced AIN in a low-middle-income country with frequent use of over-the-counter drugs. Late steroid use (? 3 weeks) was not associated with any further recovery at an additional risk of exposing patients to undue adverse effects. World J Nephrol Urol. 2022;11(1):24-30 doi: https://doi.org/10.14740/wjnu427

MO054: Histological Findings in Drug-Induced Acute Interstitial Nephritis

Abstract BACKGROUND AND AIMS Acute interstitial nephritis (AIN) represents an important cause of acute kidney injury. The most common etiology of AIN is drug-induced disease. Definitive diagnosis of AIN requires renal biopsy. Despite this, there is a lack of consensus regarding precise histological diagnostic criteria, and the clinical significance of common histological findings is uncertain. The aim of this study was to explore the histological characteristics of drug-induced AIN and to evaluate their impact on the renal outcome. METHOD We conducted a retrospective study that included patients with biopsy proven drug-induced AIN, followed in the department of nephrology of Charles Nicolle hospital in Tunis during the period between 1990 and 2019. Histological diagnosis of AIN was based on the presence of an interstitial inflammatory cell infiltrate with or without fibrosis. RESULTS During the period of the study, we collected 69 cases of biopsy proven AIN. The diagnosis of drug-induced AIN was performed in 23 patients (33%), with a medium age of 35 years. In eight patients (35%), nonsteroidal anti-inflammatory drugs were the culprit, followed by antibiotics in six patients (26%) and other drugs in three cases (13%). In six patients (26%), no single drug could be identified as the culprit, and these were classified as multidrug causes. The presence of acute kidney disease was the main indication for the kidney biopsy. All cases were characterized by a prominent tubulointerstitial inflammatory cell infiltrate. Interstitial infiltration was mild in three cases (13%), moderate in five cases (17%) and severe in 15 cases (65%). The interstitial infiltrate consisted predominantly of lymphocytes. The presence of eosinophils has been noted in 10 cases (43%). Interstitial granulomas were noted in two patients (8%). Interstitial edema and tubulitis were observed in 13 (56%) and 6 cases (26%), respectively. In seven patients (30%) interstitial fibrosis was present, and four patients (17%) had mild-to-moderate tubular atrophy, whereas tubular necrosis was present in seven cases (30%). After a mean follow up of 24 months, eight patients (35%) progressed to chronic kidney disease. Histological factors associated with poor renal outcome, were interstitial fibrosis (P ˂ 0.001) and tubular atrophy (P = 0.01). Patients with interstitial edema (P ˂ 0.001) or tubulitis (P = 0.005) had a better renal prognosis. CONCLUSION Renal biopsy is required to establish a definitive diagnosis of drug-induced AIN. Nevertheless, it is not carried out in a systematic way. The composition of cells in the interstitial infiltrate may at times be helpful in determining the etiology of AIN. In particular, the presence of a considerable proportion of eosinophils favors a diagnosis of drug-induced AIN. Moreover, during drug-induced AIN, histological data have a great prognostic value. In our study, the main histological prognostic factors were interstitial fibrosis, tubular atrophy, interstitial edema and tubulits. Further studies are needed to validate these results and establish a score based on histological data in order to predict renal outcome during drug-induced AIN.

"Double whammy" to the kidneys: an unusual etiology of acute kidney disease

Severe rhabdomyolysis could lead to myoglobinuria and acute kidney injury (AKI). Acute interstitial nephritis (AIN) is commonly caused by drugs. AIN per se can cause ‘severe’ AKI. Renal recovery is delayed when several factors are involved in the pathogenesis of AKI. Survivors of AKI require long-term follow-up. Here, we report a case where both severe rhabdomyolysis and drug-induced AIN contributed to ‘severe’ dialysis-requiring AKI. Renal biopsy was diagnostic and showed characteristic features. Steroid therapy for AIN resulted in partial recovery.

Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor-Associated Adverse Events.

Immune checkpoint inhibitors are increasingly used to treat various malignancies, but their application in patients with kidney transplants is complicated by high allograft rejection rates. Immune checkpoint inhibitor-associated rejection is a novel, poorly understood entity demonstrating overlapping histopathologic features with immune checkpoint inhibitor-associated acute interstitial nephritis, which poses a challenge for diagnosis and clinical management. We sought to improve the understanding of these entities through biopsy-based gene expression analysis. NanoString was used to measure and compare the expression of 725 immune-related genes in 75 archival kidney biopsies, including a 25-sample discovery cohort comprising pure T cell-mediated rejection and immune checkpoint inhibitor-associated acute interstitial nephritis and an independent 50-sample validation cohort comprising immune checkpoint inhibitor-associated acute interstitial nephritis, immune checkpoint inhibitor-associated T cell-mediated rejection, immune checkpoint inhibitor-associated crescentic GN, drug-induced acute interstitial nephritis, BK virus nephropathy, and normal biopsies. Significant molecular overlap was observed between immune checkpoint inhibitor-associated acute interstitial nephritis and T cell-mediated rejection. Nevertheless, IFI27, an IFN-α-induced transcript, was identified and validated as a novel biomarker for differentiating immune checkpoint inhibitor-associated T cell-mediated rejection from immune checkpoint inhibitor-associated acute interstitial nephritis (validation cohort: P<0.001, area under the receiver operating characteristic curve =100%, accuracy =86%). Principal component analysis revealed heterogeneity in inflammatory gene expression patterns within sample groups; however, immune checkpoint inhibitor-associated T cell-mediated rejection and immune checkpoint inhibitor-associated acute interstitial nephritis both demonstrated relatively more molecular overlap with drug-induced acute interstitial nephritis than T cell-mediated rejection, suggesting potential dominance of hypersensitivity mechanisms in these entities. These results indicate that, although there is significant molecular similarity between immune checkpoint inhibitor-associated rejection and acute interstitial nephritis, biopsy-based measurement of IFI27 gene expression represents a potential biomarker for differentiating these entities.

Spontaneous Perinephric Urinoma Secondary to Drug Induced Acute Interstitial Nephritis: A Case Report

AbstractUrinoma is defined as the extravasation of urine from any part of the urinary collecting system, which causes lipolysis of the surrounding fat, resulting in an encapsulated collection. The most common cause of urinoma is the direct obstruction of the urinary system. The other etiologies include trauma and postinstrumentation/surgery. Parenchymal cause for spontaneous urinoma is exceedingly rare. We present a case of a 30-year-old gentleman who presented with lower abdominal pain and was treated with a Diclofenac injection. The pain got better temporarily, but he presented again with right loin pain after 3 days. His computed tomography scan images revealed bilateral perinephric urinoma. As there was significant deterioration of renal function, he underwent a renal biopsy. The histopathology was reported as acute interstitial nephritis (AIN). Drug-induced AIN is very rarely presented with acute loin or abdominal pain due to spontaneous perinephric urinoma, as it was seen in our case.

Лекарственно-индуцированный острый интерcтициальный нефрит

Among the causes of acute interstitial nephritis, drug-induced acute interstitial nephritis accounts for 50 to 78 % of all cases. Th e review summarizes the literature data on drugs that cause acute interstitial nephritis. Search in eLibrary databases.RU, PubMed®, MEDLINE, EMBASE, manuals and guidelines, materials of adverse drug reactions databases, instructions for the medical use of drugs. it was held until October 2020. Th e most probable mechanisms of its development are considered. Most attention is paid to non-steroidal anti-infl ammatory drugs, anticoagulants, antibiotics, antitumor drugs (immune checkpoint inhibitors), which are widely used in clinical practice. Th e symptoms of drug-induced acute interstitial nephritis are variable and oft en non-specific; therefore, a kidney biopsy is required for an accurate diagnosis. The main direction of treatment of drug-induced acute interstitial nephritis is the cancellation of nephrotoxic drugs, if this condition is not feasible and/or the duration of acute interstitial nephritis is less than 3 weeks, the biopsy has minimal interstitial fibrosis and there are no serious contraindications, then the possibility of using it should be considered.

Prognosis of severe drug-induced acute interstitial nephritis requiring renal replacement therapy

Objective Drug-induced acute interstitial nephritis (DAIN) is often associated with improved outcomes, whereas some patients may still progress to chronic kidney disease (CKD). The aim of this study was to evaluate the prognosis of patients with severe DAIN requiring renal replacement therapy (RRT) at baseline, and to explore the risk factors of progression to CKD. Methods We performed a retrospective study of patients with severe DAIN confirmed by renal biopsies in our center over a 10 years period, all the patients received RRT at presentation. The clinical and pathological characteristics at baseline were recorded, and the outcomes (renal function recovered or progressed to CKD) during follow-ups were also evaluated. Univariate and multivariate logistic regression analysis were performed to identify the independent risk factors of progression to CKD. Results Seventy-two patients who met the inclusion criteria were enrolled, 13 patients (18.0%) progressed to CKD (GFR < 60 ml/min/1.73 m2) after at least 6 months of follow-up, the remaining 59 patients achieved a favorable renal function recovery. Compared with patients who achieved renal function recovery (recovery group), the patients progressed to CKD (progression group) were older and had longer interval from symptom onset to treatment with steroids. The peak serum cystatin C concentration was higher in progression group than recovery group. Higher score of interstitial fibrosis/tubular atrophy (IFTA) and more interstitial inflammatory cells infiltration were detected in renal tissue in progression group. According to multivariable analysis, higher peak cystatin C concentration (OR = 2.443, 95% CI 1.257, 4.746, p = 0.008), longer interval to treatment with corticosteroids (OR = 1.183, 95% CI 1.035, 1.352, p = 0.014) were independent risk factors of progression to CKD. The cutoff value of cystatin C concentration was 4.34 mg/L, at which the sensitivity and specificity were 76.9% and 89.3%, respectively; the cutoff value of interval to treatment with corticosteroids was 22.5 days, at which the sensitivity and specificity were 81.8% and 79.5%, respectively. Conclusion Renal function was reversible in majority of patients with severe DAIN requiring RRT when early identification and treatment. Higher peak cystatin C concentration and longer interval to treatment with corticosteroids associated with worse renal prognosis.