Diagnosis Of Acute Interstitial Nephritis Research Articles

B-243 Validating a highly automated, rapid turnaround urine biomarker assay for diagnosis of acute interstitial nephritis

Abstract Background Urinary tumor necrosis factor alpha (TNF-α) and chemokine C-X-C motif ligand 9 (CXCL9) have been identified as potential diagnostic biomarkers for acute interstitial nephritis (AIN). Although validated on standard methods like ELISA and mesoscale discovery (MSD), these platforms have a turnaround time of greater than 4hr. Ella, is a new platform which takes around 90 minutes and is more suited to be used for diagnosis of AIN in hospital setting. However, validation data for urine TNF-α and CXCL-9 in Ella assays are currently unavailable. Methods Five samples were selected for dilution-linearity and spike-recovery analysis. At the time of collection, samples were centrifuged at 2,000xg and 4°C for 10 min and the supernatant was aliquoted and stored at -80°C until assayed. We investigated dilution linearity by performing serial dilutions at three levels (Neat, 1:2, 1:4) assayed in duplicate. We performed spike and recovery experiment at three different concentration levels (high, medium, and assay diluent) by adding 5% spike volume of mixed TNF-α and CXCL-9 calibrator or assay diluent to the samples. We defined acceptance when recovery was between 80% - 120%. Intraassay %CV was calculated by averaging %CV of duplicate runs across all experiments. Inter-assay %CV was calculated by averaging %CV three levels of QC over three days. Samples were analyzed on MSD for method comparison and correlation coefficients (Pearson and Spearman) were calculated between the two measurements. Results Average recoveries and MSD comparison for TNF-α and CXCL9 are in the table below. Diluting the urine samples 4-fold yielded acceptable recoveries between 80% - 120%. Comparison between MSD and Ella yielded strong correlation for CXCL9 and moderate correlation for TNF-α. Conclusions The Ella platform can be used to measure urinary TNF-α and CXCL9 with good precision and acceptable recoveries at 1:4 dilution. Ella measurements compare favorably with those of MSD.

Urinary Biomarkers for Non-Invasive Diagnosis of Acute Interstitial Nephritis.

Urinary Biomarkers for Non-Invasive Diagnosis of Acute Interstitial Nephritis.

Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.

Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.

The diagnosis of acute interstitial nephritis caused by infection versus antibiotic-induced interstitial nephritis: a narrative review.

Acute interstitial nephritis (AIN) is a significant contributor to acute kidney injury and can be attributed to a variety of factors, including but not limited to allergens or drugs, infections, autoimmune or systemic diseases, and idiopathic forms of the disease. In some cases, AIN requires a therapeutic action according to a single specific etiology by handling the offending agent and applying an immunosuppressant. Although AIN can be diagnosed through renal biopsy, it is not able to pinpoint the precise cause when multiple causes are suspected to be present simultaneously. Such situations arise when a patient suffering from infection develops AIN during antibiotic therapy, the exact causative factor of which becomes a challenge for the clinicians to determine. This is attributed to the different approaches employed in different etiologies, wherein clinicians are required to maintain the current antibiotic therapy or augment the dose in cases of infection as AIN etiology, without resorting to immunosuppressant therapy as the primary objective is infection killing. In contrast, antibiotics as an etiology for AIN require an alternative drug from the antibiotics group, along with an immunosuppressant. In the interim, delaying the identification of the precise cause may result in interstitial fibrosis and chronic kidney disease. This narrative review highlights certain findings that can be typical of infection-associated ATIN compared with antibiotic-associated ATIN based on clinical history and physical examination, clinical presentation of different antibiotic drug classes, histopathological features, classical and novel biomarkers, serum and urine cytokines and chemokines, cellular biomarkers, and genetic biomarkers. Although these findings cannot provide conclusive and clear recommendations that can be useful in the clinical practice, they can entice researchers to conduct original research on these features to discover clear recommendations.

Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.

BackgroundAcute tubulointerstitial nephritis (AIN) is one of the few causes of acute kidney injury with diagnosis-specific treatment options. However, due to the need to obtain a kidney biopsy for histological confirmation, AIN diagnosis can be delayed, missed, or incorrectly assumed. Here, we identify and validate urinary CXCL9, an IFN-γ-induced chemokine involved in lymphocyte chemotaxis, as a diagnostic biomarker for AIN.MethodsIn a prospectively enrolled cohort with pathologist-adjudicated histological diagnoses, termed the discovery cohort, we tested the association of 180 immune proteins measured by an aptamer-based assay with AIN and validated the top protein, CXCL9, using sandwich immunoassay. We externally validated these findings in 2 cohorts with biopsy-confirmed diagnoses, termed the validation cohorts, and examined mRNA expression differences in kidney tissue from patients with AIN and individuals in the control group.ResultsIn aptamer-based assay, urinary CXCL9 was 7.6-fold higher in patients with AIN than in individuals in the control group (P = 1.23 × 10-5). Urinary CXCL9 measured by sandwich immunoassay was associated with AIN in the discovery cohort (n = 204; 15% AIN) independently of currently available clinical tests for AIN (adjusted odds ratio for highest versus lowest quartile: 6.0 [1.8-20]). Similar findings were noted in external validation cohorts, where CXCL9 had an AUC of 0.94 (0.86-1.00) for AIN diagnosis. CXCL9 mRNA expression was 3.9-fold higher in kidney tissue from patients with AIN (n = 19) compared with individuals in the control group (n = 52; P = 5.8 × 10-6).ConclusionWe identified CXCL9 as a diagnostic biomarker for AIN using aptamer-based urine proteomics, confirmed this association using sandwich immunoassays in discovery and external validation cohorts, and observed higher expression of this protein in kidney biopsies from patients with AIN.FundingThis study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awards K23DK117065 (DGM), K08DK113281 (KM), R01DK128087 (DGM), R01DK126815 (DGM and LGC), R01DK126477 (KNC), UH3DK114866 (CRP, DGM, and FPW), R01DK130839 (MES), and P30DK079310 (the Yale O'Brien Center). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Alectinib - induced acute renal failure.

Introduction: Alectinib is a potent and selective orally active tyrosine kinase inhibitor used for anaplastic lymphoma kinase-positive non-small cell lung cancer, which has a better safety profile than other inhibitors of anaplastic lymphoma kinase. We report a case of a mixed pattern of acute interstitial nephritis and acute tubular necrosis proven by renal biopsy upon starting alectinib therapy. Case report: A 68-year-old man with diabetes, hypertension, and dyslipidaemia, diagnosed with anaplastic lymphoma kinase-positive non-small cell lung cancer stage IV, had 27 days previously started alectinib 600 mg twice daily. He presented at the emergency room due to vomiting, nausea, and more dyspnoea than usual. A high creatinine level and metabolic imbalances were detected in laboratory tests. Management and outcomes: After a diagnosis of acute renal failure, the patient was admitted to hospital. Nephrotoxic drugs were suspended, and haemodialysis was required. After dismissing other causes, a probable diagnosis of acute interstitial nephritis due to alectinib was established. Corticotherapy was initiated and renal function returned to baseline levels. Renal biopsy showed a mixed pattern of acute interstitial nephritis and acute tubular necrosis. The patient was discharged, and alectinib therapy was modified to lorlatinib. No polymorphisms were found in a pharmacogenetic test. After 10 months with lorlatinib, renal function remains stable. Discussion: The relationship between acute renal failure and alectinib initiation is considered probable in this patient. Although it is an adverse effect reported in less than 1% of cases, it would be advisable to monitor renal function in this kind of patient.

Randomized control trial of prednisolone and doxycycline in patients with acute interstitial nephritis of unknown aetiology

BackgroundPatients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology.MethodA randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology (n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients’ presenting renal function to eGFR categories: 61–90 ml/min/1.73m2 (complete remission– CR) to 31–60 ml/min/1.73m2 (partial remission– PR) and 0–30 ml/min/1.73m2 no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching < 30 ml/min/1.73m2 eGFR), by 6–36 months. Analysis was by intention to treat.ResultsSeventy patients compatible with a clinical diagnosis of AIN were biopsied for eligibility; 59 AIN of unknown aetiology were enrolled, A = 15, B = 15, C = 14 and D = 15 randomly allocated to each group. Baseline characteristics were similar between groups. The number of patients with CR, PR and NR, respectively, by 6 months, in group A 3:8:2, group B 2:8:3 and group C 8:5:0 was compared with group D 8:6:1. There were no significant differences found between groups A vs. D (p = 0.2), B vs. D (p = 0.1) and C vs. D (p = 0.4).In an exploratory analysis, progression-free survival in prednisolone-treated (A + C) arms was 0/29 (100%) in comparison to 25/30 (83%) in those not so treated (B + D) arms, and the log-rank test was p = 0.02, whereas no such difference found (p = 0.60) between doxycycline-treated (B + C) arms 27/29 (93%) vs those not so treated (A + D) arms 27/30 (90%).ConclusionPrednisolone and doxycycline were not beneficial for the earliest presentation of CKDu at 6 months. However, there is a potential benefit of prednisolone on the long-term outcome of CKDu. An adequately powered steroid trial using patients reaching < 30 ml/min/1.73m2 eGFR by 3 years, as an outcome is warranted for AIN of unknown aetiology.Trial registrationSri Lanka Clinical Trial Registry SLCTR/2014/007, Registered on the 31st of March 2014.

Acute Interstitial Nephritis in the Pediatric Population: A Review of Etiologic Associations, Histologic Findings, and Clinical Outcome.

Acute interstitial nephritis (AIN) is an infrequent cause of acute kidney injury in the pediatric population with a broad range of etiologies. This retrospective review attempts to characterize AIN in the pediatric population, delineate etiologic factors, histologic features, and clinical outcome. Institutional pathology reports were queried for a diagnosis of AIN between 1/2010 and 10/2021. Archived slides and reports and clinical records were reviewed. Twenty-four patients were identified whose ages ranged from 5 to 20 years. A 8 cases (37.5%) were characterized as tubulointerstitial nephritis and uveitis (TINU), 4 cases (16.7%) were associated with an autoimmune disease, 4 cases (16.7%) were likely drug induced, and 8 cases (37.5%) had unclear etiology. Although all cases of drug induced interstitial nephritis contained eosinophils they were not exclusive to drug induced interstitial nephritis. A prominent plasma cell infiltrate was seen in both cases of Sjögren's associated interstitial nephritis. The vast majority (n = 18, 75%) showed an improved serum creatinine (<1 mg/dL) 1 year post diagnosis/at last follow-up. In this pediatric series of AIN, TINU contributed to a large subset of cases with known etiologies. On follow up, majority of the cases demonstrated recovery of renal function.

MO325: Renal Glycosuria in Acute Kidney Injury Predicts the Diagnosis of Acute Interstitial Nephritis

Abstract BACKGROUND AND AIMS Acute interstitial nephritis (AIN) is one of the most frequent causes of acute kidney injury (AKI). Interstitial inflammation can lead to tubular epithelial infiltration producing tubular dysfunction, which could be clinically detected by glycosuria (with or without Fanconi syndrome), leukocyturia, microscopic haematuria or tubular proteinuria. The aim of this study was to determine the predictive value of renal glycosuria in AKI for the diagnosis of AIN. METHOD We conducted a retrospective study of kidney biopsies performed at out centre between May 1998 and December 2021, and included patients whose kidney biopsy was performed while presenting with AKI. We excluded patients with other indications for kidney biopsy, patients with diabetes mellitus and patients who presented a serum glucose level of &amp;gt; 120 mg/dL at presentation. We registered demographic, clinical and laboratory variables at presentation of AKI, and compared patients with a final diagnosis of AIN to patients with other causes of AKI. RESULTS The study included 211 patients; 39 patients (18.5%) with a diagnosis of AIN and 172 patients (81.5%) with other diagnoses for AKI. Eight patients with AIN presented with renal glycosuria (20.5%) compared with seven patients with other causes of AKI (4.1%) (P &amp;lt; .001). Patients with AIN presented less frequently haematuria (46.2% versus 86%; P &amp;lt; .001), lower albuminuria [86 (35–151) mg/g versus 694 (136–1414) mg/g; P &amp;lt; .001], proteinuria [0.43 (0.22–0.92) g/24 h versus 1.43 (0.76–2.97) g/24 h; P &amp;lt; .001], serum glucose (89.5 ± 12 versus 94.7 ± 12.5 mg/dL; P = .019) and uric acid (6.5 ± 2.5 versus 7.8 ± 2.3 mg/dL; P = .003), and more frequently metabolic acidosis (68.6% versus 33.3%; P &amp;lt; .001) and eosinophilia (17.9% versus 5.2%; P = .007) than in patients with other causes of AKI. There were no differences in age, sex, extrarenal manifestations, serum creatinine, potassium or phosphorus levels at presentation. The presence of at least traces (≥50 mg/dL) of glycosuria had a specificity of 96.5% (92.6–98.7) for the diagnosis of AIN, with a positive predictive value of 57.1% (32.9–78.3) and a negative predictive value of 84.3% (82%–86.3%). The positive likelihood ratio was 5.9 (2.2–16) and the negative likelihood ratio was 0.82 (0.7–0.97). The presence of &amp;gt; 100 mg/dL of glycosuria had a specificity of 99.4% for the diagnosis of AIN, with a positive predictive value of 75% (24.3–96.6) and a positive likelihood ratio of 13.2 (1.4–123.8). CONCLUSION AIN can lead to proximal tubular dysfunction, which can be clinically expressed as renal glycosuria. The presence of renal glycosuria in patients with AKI guides towards the diagnosis of AIN, with an excellent specificity when glycosuria &amp;gt; 100 mg/dL.

47-Year-Old Woman With Bilateral Flank Pain

47-Year-Old Woman With Bilateral Flank Pain

Skin Biopsy in Diagnosis of Acute Interstitial Nephritis

Skin Biopsy in Diagnosis of Acute Interstitial Nephritis

S1341 Risk of Acute Interstitial Nephritis in Patients on Acute Proton Pump Inhibitor Therapy

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly prescribed medications. Studies suggest a link between PPI and acute interstitial nephritis (AIN), however data is limited. Our primary aim was to evaluate the prevalence of AIN in patients on short-term PPI therapy. Our secondary aim was to compare the risk of AIN in patients on PPI compared to H2-receptor blockers and compare adverse events (AE) . METHODS: We performed a retrospective analysis in the IBM Explorys database 5 (1999-2020), a pooled, national, de-identified clinical database of over 72 million unique patients from 26 health care networks and 300 hospitals across the United States. Patient populations were identified using SNOMED and ICD codes. PPI included were esomeprazole, omeprazole, pantoprazole and lansoprazole. The development of AIN was evaluated within 8 weeks of PPI initiation. Patients on medications commonly implicated in AIN which included NSAIDs, antibiotics, loops diuretic, H2-blockers, rifampin, and allopurinol were excluded from the study if prescribed within 30 days of initiation of PPI. Additionally, patients with systemic lupus erythematous, sarcoidosis, granulomatosis with polyangiitis, and Sjogren’s disease were also excluded from the study. The control group was defined as patients on H2 blockers with the above exclusion criteria. AE were defined as ICU admission within 7 days, hemodialysis within 2 weeks, new chronic kidney disease within 6 months of diagnosis of AIN, and new end stage renal disease within 1 year for PPI group and control group. Prevalence was reported for each PPI. Odds ratio with 95% CI were calculated for risk of AIN for each PPI compared to control group. Chi-squared test was used to compare the risk of AEs in the combined PPI group vs H2-blockers. RESULTS: Acute PPI-induced AIN comprised 0.56% (n = 1410) of total AIN patients. Prevalence of AIN in esomeprazole and omeprazole was 6 (per 10,000), pantoprazole was 18 (per 10,000) and lansoprazole was 4 (per 10,000). Pantoprazole was the only PPI associated with an increased risk of AIN (OR 1.66, 95% CI 1.51-1.84). There was no difference between risk of CKD and ESRD between PPI and control. Patients in PPI group were more likely to be senior, female, have Medicare insurance, hypertension, hyperlipidemia and heart failure. CONCLUSION: Our study shows that AIN is a rare side effect of acute PPI therapy. Pantoprazole should be used with caution perhaps in patients with underlying CKD however this needs to be validated in future studies.Figure 1Figure 2Table 1

Acute interstitial nephritis following treatment with direct-acting antiviral agents in hepatitis C virus-infected patients: A case series.

Hepatitis C virus (HCV) infection has been associated with several extrahepatic adverse clinical outcomes, including an accelerated rate of loss of kidney function in patients with chronic kidney disease (CKD) and an increased mortality in patients with CKD and kidney failure on hemodialysis. Clinical trials using direct-acting antiviral (DAA) agents have uniformly achieved sustained viral response at 12weeks (SVR12) rates of >90% in the general population as well as in patients with CKD/kidney failure on hemodialysis. Sofosbuvir is a DAA prodrug that is phosphorylated into the active metabolite GS-461203, with subsequent dephosphorylation into the inactive metabolite GS-331007. The kidneys clear both sofosbuvir and GS-331007, and its use has been associated with worsening kidney function in some studies. In the HCV-TARGET study, patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min at the initiation of sofosbuvir-based therapy had higher rates of deterioration of kidney function compared to patients with higher eGFR [1]. However, based on recent data demonstrating safety in patients with advanced CKD, the US Food and Drug Administration (FDA) approved the use of sofosbuvir-containing regimens in patients with CKD 4/5 (eGFR of less than 30 mL/min/1.73m2) and end-stage renal disease (ESRD) in late 2019. The current report describes 8 HCV-infected patients who developed acute kidney injury (AKI) with biopsy-proven acute interstitial nephritis (AIN) temporally associated with the use of DAAs. The mean age of the group was 61.3 (±6 years). The most common HCV genotype (GT) was 1a (n=7). The DAA formulations were sofosbuvir/ledipasvir (n=5), elbasvir/grazoprevir (n=2), and sofosbuvir/simeprevir (n=1). All patients achieved an SVR12. The mean serum creatinine at the initiation of DAA treatment was 1.5 mg/dL (± 0.6) and increased to 2.03 mg/dL (± 0.7) by the last day of DAA administration. The kidney biopsies were performed at a mean of 320 days (± 247) after achieving an SVR12, at which point the mean creatinine had increased to 2.3 mg/dL (± 1.4). All patients received a course of high-dose corticosteroids after the diagnosis of AIN was confirmed by biopsy. Serum creatinine levels at 3 and 6months following the completion of steroid therapy were 2.8 (±1.2) and 3.1mg/dL (±1.5), respectively. Three patients had worsening CKD and progressed to kidney failure requiring hemodialysis. These results are consistent with earlier studies demonstrating the efficacy of the DAAs in HCV-infected CKD patients. Of note, the demonstration of AIN in these patients may explain some of the AKI events reported with the use of DAAs in patients with CKD.

Renal injury in the setting of immune checkpoint inhibitor: Report of a case of hypothyroidism and the role of positron emission tomography

The use of immune checkpoint inhibitors has been increasing rapidly. Numerous untoward immune-related adverse events due to immune checkpoint inhibitors have been reported. Acute interstitial nephritis due to immune checkpoint inhibitors is one of these immune-related adverse events. Although gold standard, it is not always straightforward to perform a kidney biopsy in oncological patients. Helpful diagnostic methods are lacking. In this case report, we discuss the potential role of positron emission tomography–computed tomography on supporting the diagnosis of acute interstitial nephritis or ruling it out in the setting of acute kidney injury following treatment with immune checkpoint inhibitors. Studies are needed to assess the possible role of positron emission tomography–computed tomography for the diagnosis of acute interstitial nephritis in these subjects.

Predicting outcome in acute interstitial nephritis: a case-series examining the importance of histological parameters.

The clinical significance of common histological parameters in acute interstitial nephritis (AIN) is uncertain. We aimed to evaluate the utility of histology in predicting clinical outcomes in patients with AIN. Adult renal biopsies yielding a diagnosis of AIN between 2000 and 2015 were re-examined. Patients were divided into groups based on: (i) the percentage of non-fibrotic cortex containing inflammation (NFI score) (NFI-1=0-24%; NFI-2=25-74%; NFI-3=75-100%) and (ii) the percentage of cortex containing tubular atrophy (TA score) (TA1=0-9%; TA2=10-24%; TA3=25-100%). The primary outcome was a composite of ≥50% reduction in serum creatinine (sCr) or an estimated glomerular filtration rate (eGFR)>60ml/min/1.73m2 1year post-biopsy. From a total of 2817 native renal biopsies, there were 120 patients with AIN and adequate data for analysis. Of these, 66 (56%) achieved the primary outcome. On univariable logistic regression, NFI-3 was associated with a 16 times increased likelihood of achieving the primary outcome compared to NFI-1 [odds ratio (OR)=16, 95% confidence interval (CI)=5.2-50)]. In contrast, TA3 was associated with a 90% reduced likelihood of achieving the primary outcome compared to TA1 (OR=0.10, 95% CI=0.0-0.3). Maximal clinical utility was achieved by combining TA and NFI into a single prognostic 'TANFI' score, which had an independent predictive effect on the primary outcome in a multivariable regression model consisting of age, sex, baseline sCr and identified drug cause. In patients with biopsy-proven AIN, a lower percentage of cortical tubular atrophy and, paradoxically, a higher percentage of inflammation in non-fibrosed cortex were associated with an increased likelihood of a positive clinical outcome.

Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor-associated acute interstitial nephritis

BackgroundAcute interstitial nephritis is an immune-related adverse event that can occur in patients receiving immune checkpoint inhibitor therapy. Differentiating checkpoint inhibitor-associated acute interstitial nephritis from other causes of acute kidney injury in patients with cancer is challenging and can lead to diagnostic delays and/or unwarranted immunosuppression. In this case report, we assess the use of 18F-flourodeoxyglucose positron-emission tomography imaging as an alternative diagnostic modality in the evaluation of potential acute interstitial nephritis.Case presentationA 55-year-old woman with metastatic vulvar melanoma underwent treatment with two cycles of ipilimumab plus nivolumab, followed by seven cycles of nivolumab combined with radiation therapy. During her treatment, she developed non-oliguric acute kidney injury to a creatinine of 4.5 mg/dL from a baseline of 0.5 mg/dL. A clinical diagnosis of acute interstitial nephritis was made, and steroids were initiated, with rapid improvement of her acute kidney injury. Retrospectively, four positron-emission tomography scans obtained for cancer staging purposes were reviewed. We found a markedly increased 18F-flourodeoxyglucose uptake in the renal cortex at the time acute interstitial nephritis was diagnosed compared to baseline. In three cases of acute kidney injury due to alternative causes there was no increase in 18F-flourodeoxyglucose uptake from baseline.ConclusionsTo our knowledge, this is the first report describing increased 18F-flourodeoxyglucose uptake in the renal cortex in a patient with checkpoint inhibitor-associated acute interstitial nephritis. Our findings suggest that 18F-flourodeoxyglucose positron-emission tomography may be a valuable test for diagnosing immune-mediated nephritis, particularly in patients where timely kidney biopsy is not feasible.

Acute kidney injury in interstitial nephritis.

The purpose of this review is to describe the most common causes of acute interstitial nephritis (AIN), the diagnostic work-up and the therapeutic management. Several case series and registries have found an increasing incidence of AIN, especially among older patients. Drug-induced AIN still represents the most common cause. Early withdrawal of the culprit drug together with corticosteroid therapy remain the mainstay of treatment, although recent studies have shown that prolonged treatment beyond 8 weeks does not further improve kidney function recovery. AIN is a common cause of acute kidney injury, and therefore, physicians should suspect this entity especially in patients exposed to multiple medications. While immune-allergic reaction to numerous drugs is the most common cause of AIN, other underlying systemic diseases may also be involved, and therefore, every patient should undergo a complete diagnostic evaluation. Kidney biopsy provides the definitive diagnosis of AIN, and certain histologic features may help to identify the underlying condition. In drug-induced AIN, an early discontinuation of the culprit drug is the mainstay of therapy, and unless a rapid recovery of kidney function is observed, a course of glucocorticoid therapy should be initiated.

Overuse of Urine Eosinophils in the Diagnosis of Acute Interstitial Nephritis

Overuse of Urine Eosinophils in the Diagnosis of Acute Interstitial Nephritis

Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis.

BACKGROUNDClinical diagnosis of acute interstitial nephritis (AIN) is challenging because of lack of a diagnostic biomarker and requires a kidney biopsy. We hypothesized that AIN is mediated by specific T cell subsets such that specific T cell cytokine levels could serve as biomarkers to distinguish AIN from other causes of acute kidney disease (AKD).METHODSWe enrolled consecutive sampling participants who underwent a kidney biopsy for AKD evaluation at 2 centers between 2015 and 2018. Three pathologists independently established AIN diagnosis through review of kidney biopsies. Through univariable and multivariable analysis of 12 selected urine and plasma cytokines, we identified 2 that were diagnostic of AIN.RESULTSOf the 218 participants, 32 (15%) were diagnosed with AIN by all 3 pathologists. Participants with AIN had consistently higher levels of urine TNF-α and IL-9 than those with other diagnoses, including acute tubular injury, glomerular diseases, and diabetic kidney disease, and those without any kidney disease. As compared with participants in the lowest quartile, we noted higher odds of AIN in participants in the highest quartiles of TNF-α levels (adjusted odds ratio, 10.9 [1.8, 65.9]) and IL-9 levels (7.5 [1.2, 45.7]) when controlling for blood eosinophils, leukocyturia, and proteinuria. Addition of biomarkers improved area under receiver operating characteristic curve over clinicians' prebiopsy diagnosis (0.84 [0.78, 0.91]) vs. 0.62 [(0.53, 0.71]) and a model of current tests (0.84 [0.76, 0.91] vs. 0.69 [0.58, 0.80]).CONCLUSIONSInclusion of urinary TNF-α and IL-9 improves discrimination over clinicians' prebiopsy diagnosis and currently available tests for AIN diagnosis.FUNDINGSupported by NIH awards K23DK117065, T32DK007276, K24DK090203, K23DK097201, R01DK113191, UG3-DK114866, P30DK079310; the Robert E. Leet and Clara Guthrie Patterson Trust; and American Heart Association award 18CDA34060118.

Steroid therapy in drug induced acute interstitial nephritis- Retrospective analysis of 83 cases

Drug-induced acute interstitial nephritis (DIAIN) is a common cause of acute deterioration of renal function. Early diagnosis and discontinuation of the offending drug usually lead to recovery of renal function. Steroid administration further hastens the recovery. However, the outcome of steroid-treated DIAIN is not well studied in the Indian scenario. We aimed to study the clinical profile and one-year renal outcome of DIAIN patients treated with steroids. We performed a retrospective study in biopsy-proven acute interstitial nephritis (AIN) and presumptive DIAIN patients who did not respond to discontinuation of the offending drug after five days of the diagnosis of AIN. Eighty-three DIAIN patients were included who were treated with 500 mg of methylprednisolone for three consecutive days followed by prednisolone of 0.5-1 mg/kg tapered over four to six weeks. We evaluated clinical profile, serum creatinine (SCr), and need of renal replacement therapy at the end of one year. We divided the patients into two groups: 1st as complete responders group (CR) when SCr is <1.5 mg/dL at the end of one year and 2nd as incomplete responders (IR) when it is ≥1.5 mg/dL and evaluated the outcome between two groups. In total, there were 39 (47%) CR and 44 (53%) were IR. Diabetes mellitus, present in a significant number of cases 27 (33%) was associated with poor response to steroids. Most common offending agents recognized were antibiotics (34%), nonsteroidal anti-inflammatory drugs (25%), herbal medications (13%), proton pump inhibitors (10%), and miscellaneous drugs (18%). There was no correlation between drug category and response to steroids. Interstitial fibrosis in renal biopsy was associated with poor response to steroids (4 cases in CR and 35 cases in IR, P ≤0.0001). Neutrophilic predominance in biopsy was associated with favorable response to steroids. Initial SCr and initial the requirement of dialysis support was not helpful in predicting the response to steroids and final recovery.