Biopsy-proven Acute Interstitial Nephritis Research Articles

#2858 Immunohistochemical study reveals increased GLUT1 expression in proximal tubules of patients with acute interstitial nephritis

Abstract Background and Aims Interstitial inflammation in acute interstitial nephritis can advance into tubular epithelial cells and produce proximal tubular dysfunction, which may be clinically expressed as renal glycosuria. Previous studies have shown that the presence of renal glycosuria in acute kidney injury is a diagnostic clue for acute interstitial nephritis (AIN) with an excellent specificity. Sodium-independent glucose transporter 1 (GLUT1) is localized in the basolateral membrane of epithelial cells along the entire length of the proximal tubule, mainly in the S3 segment, and it is involved in the transcellular glucose transport. The aim of this study was to examine renal expression of GLUT1 in the proximal tubules of patients with biopsy-proven AIN. Method We identified patients with biopsy-proven AIN. After excluding patients with diabetes mellitus and patients who had received steroid treatment previous to the kidney biopsy, we selected 10 patients with biopsy-proven AIN, and we selected 10 patients with acute tubular necrosis (ATN) matched for age, proteinuria and glomerular filtration rate as the control group. An immunohistochemical study for GLUT1 was performed on the biopsies of patients with AIN and ATN. Staining intensity was graded as 0 (negative), 1+ (weak), 2+ (moderate), and 3+ (strong). GLUT1 expression was defined as focal when <50% of epithelial cells stained positive, and diffuse when >50% of the tissue showed strong staining. Results Renal glycosuria was present in 60% of the selected patients with AIN, with a median glycosuria of 150 mg/dl (IQR 0-162 mg/dl), while only 1 patient (10%) with ATN presented glycosuria (p = 0.037). All patients with AIN showed moderate or strong cytoplasmic GLUT1 staining in the epithelial cells of proximal tubules, which was significantly more intense (2+; 20% vs 11%, 3+; 80% vs 33.3%, p = 0.008) and diffuse (80% vs 22.2%, p = 0.002) than in patients with ATN. There was a tendency for positive correlation between the concentration of glycosuria and the extension of GLUT1 staining (r = 0.316, p = 0.078). Conclusion We found higher expression of GLUT1 in the cytoplasm of proximal tubular cells in patients with AIN in comparison to ATN. These findings suggest that proximal tubular injury plays a key role in the pathogenesis of AIN, leading to renal glycosuria in some cases. We hypothesize that the localization of strong GLUT1 staining in the cytoplasm of proximal tubular cells may indicate a misallocation of GLUT1 from plasma membrane where it is functional and a reversed cell polarity which might account for the observed renal glycosuria.

Tough Decision Making in Pembrolizumab-Associated Acute Interstitial Nephritis: A Case Report

Pembrolizumab is an immune checkpoint inhibitor used as a cancer therapy. The incidence of immune related adverse events in patients receiving immune checkpoint inhibitors can be as high as 59%–85%. Renal adverse effects are uncommon, but the incidence of kidney toxicity related to pembrolizumab is rising as the use of this agent becomes more frequent. We present an uncommon case of biopsy-proven acute interstitial nephritis secondary to pembrolizumab in a patient with metastatic squamous cell carcinoma at the time of his fourth scheduled cycle. Despite the good initial tumor response, pembrolizumab had to be suspended and the patient started on corticosteroids with an initial good response. On his own initiative, the patient stopped prednisolone early, leading to a rebound acute kidney injury. Pembrolizumab was not reintroduced for the risk of further renal function worsening. His clinical status declined due to the progression of the neoplastic disease, and he was referred for palliative care. This case illustrates the importance of systematizing some key points in the approach to acute interstitial nephritis secondary to pembrolizumab: the role of the differential diagnosis of acute kidney injury in a patient under an immune checkpoint inhibitor, the role of glucocorticoids and the controversy about rechallenging this drug after a related acute interstitial nephritis.

Changing Tides of Acute Interstitial Nephritis: A Retrospective Observational Study from South India.

The incidence of acute interstitial nephritis (AIN) has been increasing in recent years. The causes and outcomes of AIN have been changing with time and vary widely based on geographical region. A retrospective observational study was conducted in a tertiary care center. All (n = 6234) native kidney biopsies were reviewed from January 2016 to December 2021. All biopsy-proven AIN cases were included in the study. AIN associated with systemic diseases (such as SLE, Sjogren's, sarcoidosis, plasma cell dyscrasias), proliferative glomerulonephritis, and allograft biopsies were excluded. Among 6234 biopsies analyzed, there were 156 biopsy-proven AIN cases. The majority were in the 6th decade of life (24.4%) and males (80.8%). 50% of the patients had a history of drug intake, the most common being tenofovir (12.3%) followed by alternate forms of medications (10.3%). The majority (96.2%) presented with acute kidney injury (AKI). At the end of six months, 79.5% recovered completely, 19.2% progressed to chronic kidney disease. The presence of nephrotic range proteinuria at presentation was associated with progression to chronic kidney disease. AIN is an important cause of AKI, especially in the elderly population. Drugs are the most common cause, especially HAART follwed by alternate forms of medication. The presence of nephrotic range proteinuria was associated with increased risk of progression to chronic kidney disease.

Biopsy-proven acute interstitial nephritis after SARS-CoV-2 mRNA vaccination-adverse vaccine side effect or unrelated complication from self-medication? Lessons for the clinical nephrologist.

Biopsy-proven acute interstitial nephritis after SARS-CoV-2 mRNA vaccination-adverse vaccine side effect or unrelated complication from self-medication? Lessons for the clinical nephrologist.

Truth or dare: switching BRAF/MEK inhibitors after acute interstitial nephritis in a patient with metastatic melanoma – A case report and review of the literature

ABSTRACT Introduction The introduction of BRAF/MEK inhibitors has significantly improved overall survival of patients with BRAF V600-mutant advanced or metastatic melanoma. Most patients treated with BRAF/MEK inhibitors will experience adverse events during the course of their treatment. Kidney impairment, however, was rarely reported in the pivotal trials. To date, there are only three cases of biopsy-proven acute interstitial nephritis associated with dabrafenib and trametinib reported in the literature. Case report A 50-year-old man diagnosed with metastatic melanoma was hospitalized in August 2021, 5 months after treatment initiation with dabrafenib and trametinib. He presented with acute kidney injury, with serum creatinine of 3.34 mg/dL and eGFR of 20.3 mL/min/m². Kidney biopsy revealed acute interstitial nephritis. Management & Outcome He was treated with methylprednisolone 16 mg qd, and both dabrafenib and trametinib were permanently discontinued, with recuperation of his kidney function. Another BRAF/MEK inhibitor combination, encorafenib and binimetinib, was introduced, with preserved kidney function and excellent disease control. Discussion We report the first case of biopsy-proven interstitial nephritis in a patient treated with dabrafenib and trametinib, with successful introduction of another BRAF/MEK inhibitor combination. Although rare, clinicians should be aware of the risk of renal adverse events associated with BRAF/MEK inhibitors. Renal biopsy is mandatory in the absence of a clear explanation or rapid recovery of renal failure. In case of proven interstitial nephritis, corticosteroids should be initiated. Switching to another BRAF/MEK inhibitor combination can be considered for patients with complete recovery of renal function and limited treatment options.

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

Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy

BackgroundIn patients receiving immune checkpoint inhibitor (ICI) therapy, acute kidney injury (AKI) is common, and can occur either from kidney injury unrelated to ICI use or from immune activation resulting...

POS-034 RETROSPECTIVE STUDY OF CLINICAL PROFILE OF PATIENTS WITH BIOPSY PROVEN ACUTE INTERSTITIAL NEPHRITIS – 3 YEAR REVIEW

The incidence of biopsy-proven acute interstitial nephritis (AIN) has increased dramatically over the past decade. It is the third most common cause of acute kidney disease in hospitalized patients. It is associated with a variety of infections, drugs, and with unknown causes. The classic presentation of AIN includes fever, rash, arthralgias, eosinophilia, and acute kidney injury. Renal biopsy is considered the gold standard for diagnosis. Clinical data on AIN are very few in south India . Hence this study was done to analyse the clinical profile of the patients with biopsy proven acute interstitial nephritis.

Development and external validation of a diagnostic model for biopsy-proven acute interstitial nephritis using electronic health record data.

Patients with acute interstitial nephritis (AIN) can present without typical clinical features, leading to a delay in diagnosis and treatment. We therefore developed and validated a diagnostic model to identify patients at risk of AIN using variables from the electronic health record. In patients who underwent a kidney biopsy at Yale University between 2013 and 2018, we tested the association of >150 variables with AIN, including demographics, comorbidities, vital signs and laboratory tests (training set 70%). We used least absolute shrinkage and selection operator methodology to select prebiopsy features associated with AIN. We performed area under the receiver operating characteristics curve (AUC) analysis with internal (held-out test set 30%) and external validation (Biopsy Biobank Cohort of Indiana). We tested the change in model performance after the addition of urine biomarkers in the Yale AIN study. We included 393 patients (AIN 22%) in the training set, 158 patients (AIN 27%) in the test set, 1118 patients (AIN 11%) in the validation set and 265 patients (AIN 11%) in the Yale AIN study. Variables in the selected model included serum creatinine {adjusted odds ratio [aOR] 2.31 [95% confidence interval (CI) 1.42-3.76]}, blood urea nitrogen:creatinine ratio [aOR 0.40 (95% CI 0.20-0.78)] and urine dipstick specific gravity [aOR 0.95 (95% CI 0.91-0.99)] and protein [aOR 0.39 (95% CI 0.23-0.68)]. This model showed an AUC of 0.73 (95% CI 0.64-0.81) in the test set, which was similar to the AUC in the external validation cohort [0.74 (95% CI 0.69-0.79)]. The AUC improved to 0.84 (95% CI 0.76-0.91) upon the addition of urine interleukin-9 and tumor necrosis factor-α. We developed and validated a statistical model that showed a modest AUC for AIN diagnosis, which improved upon the addition of urine biomarkers. Future studies could evaluate this model and biomarkers to identify unrecognized cases of AIN.

Étiologies et facteurs pronostiques des néphropathies interstitielles aiguës

IntroductionAcute interstitial nephritis represents a clinically and etiologically heterogeneous group of kidney diseases. The aim of our study was to explore the main causes of biopsy-proven acute interstitial nephritis and to identify predictive factors of renal outcome. MethodsWe conducted a retrospective monocentric study which included patients with biopsy proven AIN, followed in our department during the period between 1980 and 2018. The non-recovery of kidney function or an estimated glomerular filtration rate˂60 mL/min/1.73 m2 were considered as a worse renal outcome. ResultsA total of 65 acute interstitial nephritis patients were enrolled. The mean age of patients was 41.3±16 years with a female predominance (78%). Drug-induced etiology was the most common (29%). The most frequent culprit drugs in our study were NSAID followed by antibiotics. The renal prognosis was unfavorable in 21 cases (32%). The independent predictive factors for renal outcome were : a percentage of sclerotic glomeruli greater than 15% (P=0.004), absence of interstitial edema (P˂0.001), non-use to corticosteroid therapy (P=0.02) and a delay in initiating corticosteroid therapy greater than 21 days (P=0.02). ConclusionDrugs currently represent the most common cause of acute interstitial nephritis. The renal prognosis is often favorable, but the progression can be towards chronic renal failure in the event of diagnostic and therapeutic delay. Our data suggest a beneficial influence of steroids on the outcome of acute interstitial nephritis.

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.

P0580ACUTE INTERSTITIAL NEPHRITIS RELATED TO EMPAGLIFLOZIN

Abstract Background and Aims SGLT-2 inhibitors are effective anti-hyperglycemic agents with proved cardiovascular and renal benefits. However, there have been post marketing reports of episodes of acute kidney injury (AKI), some requiring hospitalization and even dialysis in patients receiving SGLT2 inhibitors. This phenomenon may be related to volume contraction and hemodynamic changes, particularly in patients with other risk factors (such as patients on RAAS blocking agents or NSAIDS, patients with CKD). We present a case of acute interstitial nephritis (AIN) and acute tubular necrosis related to an SGLT2-inhibitor. Method Case report description. Results A 67-year-old women was admitted with weakness, dizziness and abdominal pain. Her medical history was remarkable for hypertension, diabetes mellitus, ischemic heart disease and peripheral vascular disease. Her medications included bisoprolol, losartan, amlodipine, sitagliptin and aspirin. Two months prior the current presentation, empagliflozin was prescribed by her primary physician for her diabetes mellitus. However, several days after initiation of empgliflozin she felt weak and dizzy and empagliflozin was discontinued. A week before the current presentation, empagliflozin was re-initiated by her cardiologist. The patient reported no recent illness, fevers, rash, arthralgias, respiratory symptoms or bone pain. She denied exposure to other new medications (including NSAIDS and antibiotics). On admission, blood pressure was 165/76 mm Hg. The rest of the physical examination was unremarkable. Laboratory studies revealed acute kidney injury (creatinine 3.19 mg/dL, BUN 28 mg/dL, baseline creatinine 0.9 mg/dL). Complete blood count demonstrated no eosinophilia or thrombocytopenia. Urinalysis showed a few leukocytes but no red cells or casts. The urine protein to creatinine ratio was 5160 mg of protein per gram creatinine. Abdominal ultrasonography showed normal-size kidneys and no hydronephrosis. Immunologic and infectious serologies were unremarkable. over several days the patient became oligo-anuric and creatinine peaked to 9.22 mg/dL and hemodialysis was initiated. Empiric treatment with prednisone was given and a renal biopsy was performed. Four glomeruli were seen on light microscopy. The glomeruli were normocellular. An interstitial infiltrate of lymphocytes and small numbers of eosinophils were seen. Thining of the renal tubular brush border with intra-tubular necrotic content was a also seen. Immunofluorescence was negative. The findings were compatible with acute interstitial nephritis and acute tubular necrosis (Figure 1). The patient was discharged with a regimen of intermittent hemodialysis and steroid therapy. Three months later, urine output and kidney function improved, and the patient was weaned off dialysis. Conclusion In this case report, we describe previously unreported histologically proven AIN likely related to empagliflozin exposure. Although SGLT2 inhibitors have been reported to be associated with AKI it has been supposed to be related to volume contraction and hemodynamic changes. As virtually any drug can cause AIN, further proof of the drug's causation in our case was an onset of renal dysfunction with re- institution of empagliflozin, biopsy-proven AIN and absence of other drugs, infection or systemic disease that might cause AIN. With the dramatic increase in use of SGLT-2 inhibitors worldwide, treating physicians should be aware of AIN as a possible cause of AKI in this context.

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.

Acute interstitial nephritis (AIN) following immune checkpoint inhibitor (ICI) therapy in metastatic RCC (mRCC) as a potential predictor of response.

674 Background: ICIs such as nivolumab (N) have improved outcomes in mRCC patients (pts), but are also associated with immune-related adverse events. As has been shown in melanoma, we hypothesized that pts experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we evaluated whether pts with nivolumab-induced AIN (N-AIN) exhibited improved outcomes. Methods: We identified all patients with mRCC at UT Southwestern Medical Center from 2014 - 2018 who received at least one dose of N. We extracted creatinine (Cr) values over the entirety of each pt's N treatment course from the electronic medical record. Pts with a 1.5 fold Cr increase over baseline were investigated. The diagnosis of N-AIN was made by biopsy or by clinical criteria (timing of kidney injury, laboratory analysis, and exclusion of other causes). Results: We identified 177 mRCC pts who received at least one dose of N, 36 of whom had at least a 1.5 fold increase in Cr over baseline while on treatment. Of those, two had biopsy-proven AIN and one was clinically diagnosed, resulting in an incidence of 1.7%. Two received N monotherapy after first line, and the third in combination with ipilimumab as initial therapy. The earliest case of N-AIN occurred 1.5 months from N onset, and the others were diagnosed at 11 and 12 months. Of the 3 pts, one had a partial response lasting 2 years, and the other two had a complete response which is ongoing in both pts with over 2 years of follow up. In all 3 cases, N-AIN was treated with cessation of N and prednisone with a return to baseline kidney function. None required dialysis. Conclusions: AIN is a rare event with N, but it may portend a higher likelihood of response. One possible explanation is antigenic crossover between normal renal tubular cells and mRCC, resulting in a robust immune response.

Inflammatory leucocyte infiltrates are associated with recovery in biopsy-proven acute interstitial nephritis: a 20-year registry-based case series.

BackgroundAcute interstitial nephritis (AIN) is a renal injury causing renal function deterioration and requiring renal replacement therapy (RRT) in a substantial number of cases. Therapy is based on withdrawal of suspicious causative drugs or the underlying diseases and/or steroid application if renal function is not restored after cessation of the underlying condition. Hard clinical evidence for augmenting steroid therapy is not available.MethodsWe reviewed the course and diagnosis for >20 years among all 1126 biopsied samples of our tertiary renal centre.Results49 (4.4%) were diagnosed with primary AIN, corresponding to an annual incidence of 1/100 000 population; 17 out of 49 biopsy-proven AIN patients required short-term or long-term (n = 5) RRT. According to a combined outcome criterion of coming off dialysis and/or reaching serum creatinine <200 µmol/L, 19 patients reached recovery whereas 20 did not. Among 39 patients with a comprehensive clinical and histopathological data set, presence of cortical scars, AIN histological activity (acute leucocyte infiltrates) and proteinuria were baseline parameters discriminating significantly between groups with or without recovery. No associations with the presence of specific drugs were found. Therapeutic use of steroids was associated with a lower probability of recovery (P = 0.008), presumably due to inclusion bias.ConclusionsFollowing our basic finding of the importance of histopathological parameters of acuity associated with recovery, we argue for the inauguration of grading measures to characterize this issue quantitatively and make it usable for future controlled investigations. Finally, we provide a suggestion for a therapeutic algorithm in the management of AIN.

MON-248 HERBAL BITTER: A RARE CAUSE OF ACUTE TUBULOINTERSTITIAL NEPHRITIS

Acute interstitial nephritis is an immunologically driven condition characterised by an inflammatory infiltrate in the renal interstitium. The use of herbal remedies has increased globally and has been described as a risk factor for the development of kidney injury, causing a variety of renal syndromes. We present a unique case of biopsy-proven acute interstitial nephritis following ingestion of an herbal bitter health drink, which was associated with a skin rash and eosinophilia. A 72-year-old-man presented with a 1-week history of general malaise, rash and fevers. His physical examination revealed a widespread maculopapular rash and pitting oedema to the knees but otherwise a normal examination including vital signs. His blood pressure on admission was 124/70. Four days into admission, his renal function deteriorated with a serum creatinine level rising to 411μmol/L (baseline of 98 μmol/L). One week into admission, he had a peak serum creatinine of 651 and was also oligouric. A renal biopsy revealed an interstitial infiltrate with a rich population of eosinophils. The findings were diagnostic of tubulointerstitial nephritis; the presence of eosinophils supporting a drug-induced cause. He had no recent alteration to his medications. On further questioning, the patient noted that one month prior to admission, he had started consuming an herbal bitter health drink. He was treated with intravenous methylprednisolone and a tapering dose of prednisolone, with the patient’s kidney function returning to baseline four weeks after the commencement of steroids. The herbal health drink ingested by the patient in this case, comprised of a combination of bitter herbs, consisting of a blend of seven herbal bitters. To the best of our knowledge, this is the first case of biopsy-proven acute interstitial nephritis induced by this multi-herbal health drink. This case report highlights the importance of taking a thorough medical history including establishing the use of over-the-counter medication and herbal remedies in the drug history. Furthermore, the importance of a prompt histological diagnosis in the form of a kidney biopsy is warranted, particularly in the case of drug-induced acute interstitial nephritis, as the mainstay of treatment involves cessation of the causative agent.

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.

Acute interstitial nephritis in the military hospital of Morocco: Clinical features and renal outcomes.

Acute interstitial nephritis (AIN) is a common cause of acute kidney injury, possibly with increasing incidence over recent years; therefore, epidemiological studies provide important information for clinical practice and investigations. The aim of this retrospective study was to describe the clinical features and outcome of patients with biopsy-proven AIN in a region of Morocco. All native renal biopsies (January 2008 to December 2017) on adults were reviewed, but only AIN cases were analyzed. Of the 407 renal biopsies performed in this period, 30 patients were included. The mean age of the patients was 47.1 ± 16.7 years; female gender was preponderant (60%). At the time of biopsy, the serum creatinine level was 33.9 ± 11.8 mg/L. The classic triad of fever, skin rash, and eosinophilia occurred in three (10%) patients. The common causes of AIN were drugs in 13 (43.3%) patients followed by autoimmune diseases in 11 (33.3%) patients. At six months postbiopsy, 26.7%, 33.3%, and 40% had partial, complete, and no recovery, respectively. In this study, a good outcome was associated with autoimmune diseases (P = 0.02) and with a higher intensity of interstitial edema (P = 0.01). However, a presence of a granuloma (P = 0.04), a higher percentage of interstitial fibrosis (P <0.01), and glomerulo-sclerosis (P <0.01) were associated with no recovery and steroids seem to have no effect in the recovery (P = 0.14).This information provides a contribution toward understanding the epidemiology of acute renal failure in Africa, with implications in planning future prospective studies.

Drug-induced acute interstitial nephritis: Prospective randomized trial comparing oral steroids and high-dose intravenous pulse steroid therapy in guiding the treatment of this condition.

The most important aspect of treating drug-induced acute interstitial nephritis (AIN) is timely discontinuation of the offending drug. Steroids, oral as well as intravenous (IV), are used in the treatment of drug-induced AIN. The present study was undertaken to compare the efficacy of oral prednisolone versus IV suprapharmacological doses of corticosteroids in the treatment of drug-induced AIN. This prospective randomized controlled study included drug-induced AIN diagnosed on histopathology over a period of two years. Patients were randomized to oral prednisolone (Group A) 1 mg/kg for two weeks or pulse methylprednisolone (Group B) 30 mg/kg for three days (maximum 1 g) followed by oral prednisolone 1 mg/kg for two weeks, tapered over two weeks. Response was reported as complete remission (CR) [improvement in estimated glomerular filtration rate (eGFR) to ≥60 mL/min/1.73 m2], partial remission (PR) (improvement but eGFR <60 mL/min/1.73 m2), or nonresponders to steroids (no CR/PR). Steroid therapy was instituted to 31 biopsy-proven AIN cases (Group A - 16 and Group B - 15). Drugs implicated in the causation of AIN included pantoprazole, diclofenac, rifampicin, naproxen, aspirin, imipenem, piroxicam, cefixime, lornoxicam, Chinese herbs, etoricoxib, ciprofloxacin, and phenytoin. There was no difference in the baseline parameters between the two groups. At the end of follow-up, 58.06% achieved CR and 41.93% achieved PR. In Group A, nine (56.2%) achieved CR and seven (43.7%) achieved PR. In Group B, nine (60%) achieved CR and six (40%) achieved PR. There was no significant difference between the two groups. Pulses of high doses of corticosteroids have a significant but transient anti-inflammatory effect. Both oral and IV suprapharmacological doses of corticosteroids are equally effective in the treatment of drug-induced AIN, if used early.