Cause Of Acute Interstitial Nephritis Research Articles

Enfermedades renales tubulointersticiales. Nefritis intersticial aguda

Acute interstitial nephritis (AIN) is characterised by an inflammatory infiltrate, oedema and tubulitis in the renal interstitial, and it usually leads to acute deterioration of kidney function. AIN refers to the acute form of the disease which causes swift deterioration of kidney function, while the chronic forms have a longer course in which histology detects more fibrosis. The definitive diagnosis of both pathologies is therefore histological, as there are currently no non-invasive markers to confirm or exclude them. Although its exact incidence is very hard to determine, it varies from 5%-27%, progressively increasing in incidence mainly in the elderly, which may be due to their increasing exposure to drugs and other trigger mechanisms. The causes of AIN have undergone a drastic change, as now the most common aetiology consists of pharmacological agents (more than 75%).

The Challenges of Acute Interstitial Nephritis: Time to Standardize.

Acute interstitial nephritis (AIN) is a well-known cause of acute kidney disease (AKD) and CKD and is associated with progression to ESKD (1⇓⇓⇓⇓–6). Accordingly, it represents an important problem for clinicians caring for these patients. AIN is primarily an immune-mediated kidney injury triggered by use of certain medications, in particular antibiotics, PPIs, NSAIDs, and immune checkpoint inhibitors (ICPIs), or by autoimmune diseases, such as Sjogren syndrome, sarcoidosis, IgG4-related tubulointerstitial disease, and TINU. In developed countries, medications are the most common cause of AIN (>70%), whereas the number approximates 50% in developing countries. Infectious agents are a less common cause of AIN, except in developing countries. The overall incidence of AIN in kidney biopsy registries is 2%–5%, whereas AIN is observed in approximately 15%–20% of patients with AKI or AKD who undergo kidney biopsy (1⇓–3). The actual number is likely higher as many patients with AKI/AKD do not undergo biopsy and are presumed to have acute tubular injury (ATI). Importantly, diagnosing AIN clinically is often quite challenging, making kidney biopsy a frequent requirement to definitively confirm the diagnosis and guide therapy (Figure 1). Furthermore, delayed or missed AIN diagnosis leads to ongoing inflammation with resulting interstitial fibrosis, tubular atrophy, and permanent kidney damage, which may be the explanation for CKD occurring in 40%–60% of patients after an episode of AIN (4,5). Approximately 2% of CKD is considered to be due to AIN, which is equivalent to 10 million prevalent worldwide cases. Furthermore, AIN is the primary cause of ESKD in 3%–4% of incident patients (6). It is one of the few potentially treatable causes of AKI if identified and treated early. In view of these data, three key challenges that limit the diagnosis and management of patients suspected of having …

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.

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.

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.

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.

The increasing rates of acute interstitial nephritis in Australia: a single centre case series

BackgroundThe Australian Institute of Health and Welfare’s first report into acute kidney injury demonstrated a significant increase in the incidence of acute-tubulo interstitial nephritis, the ICD-10 code representing both acute interstitial nephritis and pyelonephritis, in women aged less than 55 years. In contrast, recent case series have reported rising rates of drug induced acute interstitial nephritis predominantly among elderly patients. Due to several limitations with the Australian Institute of Health and Welfare report, this new trend requires further investigation to determine if rates of acute interstitial nephritis are truly increasing among younger Australian women.MethodsPatients who underwent a renal biopsy at a single center from 2000 to 2015 were reviewed and those with biopsy confirmed acute interstitial nephritis were selected. Cause of acute interstitial nephritis, patient demographics, co-morbidities and renal indices for these patients when available were recorded and compared.ResultsEight hundred ninety-eight patients who underwent renal biopsy from 2000 to 2015 were reviewed and 40 patients were identified with biopsy confirmed acute interstitial nephritis. The rate of acute interstitial nephritis increased significantly over the study period (4 patients/2.2% of biopsies performed in 2000–03 vs. 19 patients/6.7% of all biopsies performed in 2012–15; p = 0.002). There was a marked increase in the number of women with AIN in the last four years of the study (2 patients and 2.1% of biopsies performed in women in 2000–2003 compared with 13 patients and 9.0% of biopsies performed in women in 2012–2015). Immune mediated causes of acute interstitial nephritis and NSAID associated AIN were more common in women (9 females vs. 3 males), occurred more frequently in the last eight years of the study and predominantly in patients under 55 years of age.ConclusionsOur study demonstrates a significant increase in the number of patients with biopsy confirmed AIN. Also, we provide preliminary evidence in support of an increase in rates of younger women with immune mediated acute interstitial nephritis. These results support the findings of the Australian Institute of Health and Welfare and suggest that younger women may be at higher risk of immune mediated and NSAID associated acute interstitial nephritis.

Clinical profile and outcome of patients with biopsy-proven acute interstitial nephritis in Cape Town: a 10-year review .

Acute interstitial nephritis (AIN) is a common cause of acute kidney injury that has not been adequately characterized in Sub-Saharan Africa (SSA) despite an increasing use of potentially inciting agents for the treatment of human immunodeficiency virus (HIV) and tuberculosis in the region. A retrospective audit of records of patients with biopsy-proven AIN diagnosed at Groote Schuur Hospital, Cape Town from the 1^st of January, 2006, to the 31^st of December, 2015. 54 patients with biopsy-proven AIN were reviewed. The majority were of black African origin (59.2%), with HIV (42.8%) and HIV-tuberculosis coinfection (30.5%) as the most common comorbidities. Drug-related AIN was seen in 38 (67.9%) patients, with rifampicin as the most often implicated medication. Probable drug-related AIN was seen in 3 (5.4%) patients, infection-related AIN in 8 (14.3%), and unspecified causes in 4 (7.4%). AIN was suspected in 44.6% of patients before biopsy. 18 patients (34%) received hemodialysis, while 19 (35.2%) were treated with corticosteroids. Complete renal recovery at 30 and 90 days was seen in 23 (42.6%) patients and 24 (45.3%) patients, respectively, with the majority seen among those with drug-induced AIN. Six (11.1%) patients died; 4 (10.5%) of the patients were in the drug-related group. There was no correlation between degree of interstitial inflammation and severity of renal failure (p=0.10). On multivariate logistic regression, drug-related causes of AIN were predictive of complete recovery at day 30 (OR 16.63; 95% CI: 1.71-161.6, p=0.02), and presence of interstitial fibrosis reduced likelihood of recovery (OR 0.03; 95% CI 0.002-0.46, p=0.012). Steroid use did not influence partial recovery (OR 0.59, 95% CI 0.17-1.77; p=0.32) or complete recovery (OR 3.38, 95% CI 0.38-30.39, p=0.28). AIN is common in patients with HIV or those on treatment for tuberculosis. Drug-related AIN is often associated with improved outcomes. This is particularly reassuring in the SSA region where the use of potentially-inciting medications is rife from a high burden of HIV and tuberculosis. .

Acute interstitial nephritis in the south of Iran; an observational study

Background Acute interstitial nephritis (AIN) is an emerging cause of acute kidney injury (AKI) during the recent years. Objectives: There is no data about prevalence, causes, clinical manifestation and outcomes of AIN in our region. Hence, in this study we aimed to find the prevalence of AIN and describe the causes, clinical presentation, and the outcome of AIN in the native kidney biopsies. Patients and Methods: We reviewed 934 native kidney biopsies from 2006 to 2014 and collected the data of patients with the diagnosis of AIN including medical history, clinical findings, para-clinical data, pathologic findings, treatment and outcomes. Results: Prevalence of AIN in our center during 2006 to 2014 was 2.5% of all renal biopsies. The common cause of AIN in our study was drugs. Of those patients admitted to hospital due to AIN, 17 patients (70.8%) received corticosteroid, five of them (29.4%) received pulse of corticosteroid, and 12 patients (70.6%) received oral drug. Around, 54.2% of the patients had hemodialysis during admission. Eight patients had received both dialysis and corticosteroid. Two of them (8.3%) remained on dialysis and 8 (33.3%) developed chronic kidney disease, but 14 (58.3%) patients recovered. Conclusions: The prevalence of AIN in our study is comparable to other studies and we found the great impact of medications on development of AIN.

Quiz Page March 2016: A 60-Year-Old Man With Fever, Night Sweats, and Acute Kidney Injury

Quiz Page March 2016: A 60-Year-Old Man With Fever, Night Sweats, and Acute Kidney Injury

A case of acute interstitial nephritis and granulomatous hepatitis induced by ingesting quinine.

Quinine is used for the treatment of malarial infection, though not in common use. It is especially valuable for the parenteral treatment of severe illness owing to drug-resistant strains of Plasmodium falciparum. Quinine is also known to occasionally cause acute renal failure (ARF). Although quinine is listed in some reviews as a cause of acute interstitial nephritis, most cases of quinine-associated acute renal failure have been attributed to the hemolytic-uremic syndrome (HUS). Only two cases of acute renal failure due to acute interstitial nephritis associated with quinine have been reported [1, 2]. To our knowledge, there have been 6 reported cases of quinine-induced hepatic granuloma [3-8]. We report a case of quinine-induced acute interstitial nephritis (AIN) along with granulomatous hepatitis, both of which were confirmed on biopsy. A 50-year-old Nigerian man was admitted to the hospital with complaints of fever and general fatigue. He had been prescribed quinine as an antimalarial drug in a Nigerian hospital. The patient was febrile and showed nonoliguric ARF and liver dysfunction. In this case, liver injury showed gradual and spontaneous resolution after discontinuing quinine, and ARF resolved after treatment with oral prednisolone.

Biopsy-Proven Acute Interstitial Nephritis, 1993-2011: A Case Series

Acute interstitial nephritis (AIN) is an important cause of acute kidney injury, especially in hospitalized patients. The cause and outcome of AIN, particularly that due to drugs, is changing with prevalent medication use. The effectiveness of steroids for treatment of AIN is debated. Case series. 133 patients with biopsy-proven AIN from 1993 through 2011 at a single center. Recovery of kidney function by 6 months, either complete, partial, or none. Complete recovery was defined as improvement in serum creatinine level to within 25% of baseline (or < 1.4 mg/dL), and partial recovery, as a ≥ 50% decrease in serum creatinine level from its peak value but not reaching within 25% of its baseline value. Causes of AIN included drugs (70%), autoimmune diseases (20%), and infections (4%). Drug-induced AIN was due to antibiotics in 49%, proton pump inhibitors (PPIs) in 14%, and nonsteroidal anti-inflammatory drugs (NSAIDs) in 11%. Overall, the top 3 drug causes were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%). Patients with drug-induced compared to non-drug-induced AIN were older and had higher baseline kidney function, but more severe acute kidney injury. Patients with PPI-induced AIN were older, were less symptomatic, and had longer durations of drug exposure and longer delays in getting kidney biopsy and steroids than for antibiotic-induced or NSAID-induced AIN. At 6 months postbiopsy, 49% of patients with drug-induced AIN treated with steroids achieved complete recovery; 39%, partial recovery; and 12%, no recovery. Correlates of poor recovery included a longer duration of drug exposure (15 vs 30 vs 130 days for complete, partial, and no recovery, respectively; P = 0.04) and longer delay in starting steroid therapy (8 vs 11 vs 35 days, respectively; P = 0.05). Retrospective study, selection bias in patients who had kidney biopsy, single-center experience. The cause of AIN may be shifting; PPIs are emerging as an important contributor to this disease. Delays in discontinuation of the culprit drug and in initiating steroid treatment adversely affect recovery of kidney function.

Acute Interstitial Nephritis With Predominant Plasmacytic Infiltration in Patients With HIV-1 Infection

We describe a new form of acute interstitial nephritis with predominant plasmacytic infiltration in 2 patients with active human immunodeficiency virus 1 (HIV-1) infection. Clinical features included acute kidney injury and proteinuria, but no sicca syndrome. Acute kidney injury was characterized by a high serum creatinine level and nephrotic syndrome with no hematuria or leukocyturia. Kidney biopsy specimens from both patients showed interstitial infiltration by mononuclear cells composed mainly of CD138(+) plasmacytes and diffuse effacement of podocyte foot processes with no deposits. In one patient with Guillain-Barré syndrome, a sural nerve biopsy showed plasmacyte infiltration and immunohistochemistry was strongly positive for HIV-1 p24 protein. In both patients, minor salivary glands and bone marrow were infiltrated by lymphocytes, consistent with B-cell activation induced by HIV-1 infection. Other common causes of acute interstitial nephritis, including B-cell lymphoma and diffuse infiltrative lymphocytosis syndrome, were actively looked for and excluded. Treatment with highly active antiretroviral therapy was effective; symptoms rapidly improved, serum creatinine level decreased, and proteinuria resolved. Exclusion of other common known causes of acute interstitial nephritis and the dramatic response with highly active antiretroviral therapy suggests HIV-1 as a likely cause. The acute interstitial nephritis probably was induced by HIV-1-driven nonspecific B-cell activation. Further investigations are needed to confirm the direct pathogenic role of HIV-1.

Mycobacterial-immune reconstitution inflammatory syndrome: a cause of acute interstitial nephritis during HIV infection

Kidney injury during HIV infection encompasses a wide variety of disorders, including acute interstitial nephritis. We report a case of acute granulomatous interstitial nephritis related to a mycobacterial-triggered immune reconstitution inflammatory syndrome (IRIS) in an HIV-infected patient. IRIS is an emerging health concern during HIV infection and should be considered in the diagnostic frame of acute renal failure during immune restoration.

257 Acute Interstitial Nephritis Associated with Sitagliptin Use

ACUTE INTERSTITIAL NEPHRITIS ASSOCIATED WITH SITAGLIPTIN USE Mohammad Quasem, Yan Liu. United Health Services Hospitals, Binghamton, New York, USA. Sitagliptin is an oral hypoglycemic agent classified under Dipeptidyl 4 (DPP-4) inhibitor. It is used for treatment of type 2 diabetes. Apart from hypoglycemia, common adverse effects are mainly nasopharyngitis (5%) and gastrointestinal (2-4%). No report of acute interstitial nephritis (AIN) from Sitagliptin has, so far, been reported although a case of rhabdomyolysis and acute renal failure (ARF) from combination of Sitagliptin and Simvastatin was reported about two years ago (Diabet Med: 2008). We present a patient who developed ARF after starting Sitagliptin. She developed an erythematous rash day after Sitagliptin was started which rapidly spread all over her body. At the same time, her renal function also got worse with serum creatinine as high as 4.2 after six days (baseline serum creatinine 1.5-1.7) with peripheral blood leukocytosis and eosinophilia. Sitagliptin was discontinued and patient was put on steroid. Renal function gradually returned to baseline. Drugs are the most common cause of AIN. Although kidney biopsy was not done, the clinical scenario, the time course of drug exposure and improvement of renal function on withdrawal (plus steroid) suggested Sitagliptin was the cause. With the widespread use of Sitagliptin, increased awareness for AIN is needed.

Characteristics of Patients with HIV and Biopsy-Proven Acute Interstitial Nephritis

The objective of this study was to describe the characteristics of patients with HIV infection and biopsy-proven acute interstitial nephritis (AIN). Pathology reports were reviewed for patients who had HIV infection and underwent renal biopsy at Johns Hopkins Hospital from January 1, 1995, through January 1, 2008. Patients who received a diagnosis of AIN without evidence of HIV-associated nephropathy were identified, and their clinical course was reviewed up to 18 months after biopsy. Of 262 biopsies, 29 (11%) patients who had AIN without evidence of HIV-associated nephropathy were identified. The mean age at the time of biopsy was 47.5 years (range 28 to 71 years), 17 (59%) were men, and 23 (79%) were black. The majority (62%) of patients were on antiretroviral therapy, 59% were current or former intravenous drug users, and 62% had hepatitis C co-infection. Drugs were identified as the cause of AIN in the majority (72%) of cases. Nonsteroidal anti-inflammatory drugs were most commonly implicated, followed by sulfamethoxazole/trimethoprim. Antiretroviral therapy was identified as the cause in only three cases. None of the patients presented with the classic triad of fever, rash, and pyuria, and only seven (24%) patients presented with <1 g/d proteinuria. In our series, AIN was prevalent (11%) and was often drug induced. AIN should not be excluded from the differential diagnosis on the basis of absence of the classic clinical triad of fever, rash, and pyuria.

Tubulointerstitial nephritis with uveitis syndrome: A case report and review of literature

Tubulointerstitial nephritis with uveitis (TINU) syndrome is an unusual and under diagnosed cause of acute interstitial nephritis. The interstitial nephritis may precede, follow or develop concurrent to the uveitis. About 200 cases have been reported worldwide with only a single case reported from India. We report a 16-year-old male with TINU syndrome.

Steroid Therapy for Drug-Induced Acute Interstitial Nephritis

Drugs are an important cause of acute interstitial nephritis (AIN). Although drug-induced AIN sometimes is treated with corticosteroids, no randomized

Proton pump inhibitors and acute interstitial nephritis: Report and analysis of 15 cases

Although proton pump inhibitors (PPI) are usually safe and effective therapeutic agents, serious adverse effects can occur. The aim of the present study was to report and analyse the clinical features of 15 patients with acute interstitial nephritis (AIN) and acute renal failure from PPI that were referred to renal services in Auckland over a period of 3 years. The clinical presentation, therapeutic drugs, demographic details and renal outcome of the patients were considered. The population at risk and total PPI exposure were able to be defined. The diagnosis of AIN was made by renal biopsy in 12 cases. In all patients, the time-course of drug exposure and improvement of renal function on withdrawal suggested PPI were causal. The median patient age was 78 years. The mean baseline serum creatinine level was 83 micromol/L, peak level 392 micromol/L, and recovery level 139 micromol/L. The erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at the time of diagnosis in the 11 and 12 patients, respectively, where this information was collected (ESR mean 85 mm/h, and C-reactive protein mean 81 mg/L). AIN occurred at 8 per 100 000 patient years (95% confidence level 2.6-18.7 per 100 000 patient years). Although four patients presented with an acute systemic allergic reaction, 11 were asymptomatic with an insidious development of renal failure. PPI are now the most commonly identified cause of AIN in the Auckland area. Recovery occurs after withdrawal of the drug but is often incomplete. Early diagnosis may be facilitated by clinician awareness of the insidious onset of renal failure, and an elevated erythrocyte sedimentation rate and C-reactive protein.

Proton Pump Inhibitors and Acute Interstitial Nephritis

Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, and their usage worldwide is increasing. Although well-tolerated, there have been case reports and a recent case series implicating these drugs in acute interstitial nephritis (AIN) and progression to acute renal failure (ARF). The aim of this study was to investigate how widespread this complication is in Australia, to identify which PPIs are implicated, and to establish whether PPI-induced AIN is a class effect. We undertook a retrospective case review of potential cases at 2 teaching hospitals and a review of registry data from the Therapeutic Goods Administration of Australia (TGA). Parameters sought included the drug implicated, concurrent medications, symptoms, signs, serum creatinine, and time of onset after prescription. We identified 18 cases of biopsy-proven PPI-induced AIN causing ARF in the retrospective case review, which is the largest hospital-based case series to date. The TGA registry data identified an additional 31 cases of "biopsy proven interstitial nephritis." An additional 10 cases of "suspected interstitial nephritis," 20 cases of "unclassified acute renal failure," and 26 cases of "renal impairment" were also identified. All 5 commercially available PPIs were implicated in these cases. With the ever more widespread use of this class of medications, PPI-induced AIN is likely to become more frequent. There is now evidence to incriminate all the commercially available PPIs, suggesting there is a class effect. Failure to recognize this entity might have catastrophic long-term consequences including chronic kidney disease. Increased awareness might facilitate more rapid diagnosis and management of this potentially reversible condition.