Biopsy-proven first dose of oxaliplatin-induced acute tubular necrosis leading to end-stage renal failure: a case report.

BACKGROUND: Oxaliplatin is an anticancer therapy for pancreatic, gastric, and colorectal cancers. It is also used in patients with carcinomas of unknown primary sites. Oxaliplatin is associated with less frequent renal dysfunction than other conventional platinum-based drugs such as cisplatin. Albeit, there have been several reports of acute kidney injury with frequent use. In all cases, renal dysfunction was temporary and did not require maintenance dialysis. There have been no previous reports of irreversible renal dysfunction after a single dose of oxaliplatin. CASE PRESENTATION: Previous reports of oxaliplatin-induced renal injury occurred after patients received multiples doses. In this study, a 75-year-old male with unknown primary cancer and underlying chronic kidney disease developed acute renal failure after receiving the first dose of oxaliplatin. Suspected of having drug-induced renal failure through an immunological mechanism, the patient was treated with steroids; however, treatment was ineffective. Renal biopsy ruled out interstitial nephritis and revealed acute tubular necrosis. Renal failure was irreversible, and the patient subsequently required maintenance hemodialysis. CONCLUSIONS: We provide the first report of pathology-confirmed acute tubular necrosis after the first dose of oxaliplatin which led to irreversible renal dysfunction and maintenance dialysis.

Pathological Features of Recovery or Progression in Acute Tubular Necrosis: Single Centre Study.

Acute tubular necrosis (ATN) is the most important and frequent cause of acute kidney injury (AKI). Controversy exists concerning the role of renal biopsy in the evaluation of ATN prognosis. We aim in our study to evaluate the role of renal biopsy for the detection of recovery and progression and rate of recovery of ATN. The study was designed to include all biopsies with the diagnosis in ATN in adults >21-year-old, from January 2016 to December 2018. Biopsies were recruited retrospectively and were reviewed by three pathologists and quantitated. Four histological ATN features were evaluated. Flattening cells, distension or dilatation, debris, and vacuolation and for each a score were attributed as follows: 0 = less than 5% of section, 1 = 6%-25%, 2 = 26%-50%, 3 = >50%. Thirty-five patients with 35 renal biopsies were analyzed. Flattening was seen <5% in nine patients, 6%-25% in 15 patients, 26%-50% in six patients. and >50% in five patients. Dilatation was seen <5% in 11 patient, 6%-25% in 10 patients, 26%-50% seen in six patients, and >50% in eight patients. The presence of debris was seen in <5% in 12 patients, 6%-25% in 12 patients, 26%-50% seen in six patients, and >50% seen in five patient. Vacuolation was seen in 5% in eight patients, 6%-25% in 14 patients, 26%-50% in seven patients, and >50% in six patients. It was found that flattening <5% and dilatation <5% and dilatation >50% in renal biopsy are the good indicators for recovery and good prognosis of cases of ATN, in addition debris <5% and >50% and vacuolation <5% are also good indicators for recovery and good prognosis of cases of ATN. On the other hand, flattening from 6% to 25% and from 26% to 50%, dilatation from 6% to 25%, debris from 26% to 50% and vacuolation >50% are also indicators for delayed recovery and poor prognosis of cases of ATN. Renal biopsy in AKI with the diagnosis of ATN with scoring system of flattening, dilatation, debris, and vacuolation can point to indication of recovery or progression of these cases.

Urinary NGAL as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Cirrhosis: A Prospective Study.

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 µg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] µg/g creatinine) from prerenal AKI (45 [0, 154] µg/g) or HRS (110 [50, 393] µg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] µg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Urinary cytology: a potential tool for differential diagnosis of acute kidney injury in patients with nephrotic syndrome.

OBJECTIVE: Acute tubular necrosis (ATN) is a frequent cause of acute kidney injury (AKI). In patients with nephrotic syndrome (NS), AKI demands the differential diagnosis between ATN and rapidly progressive glomerulonephritis. In some cases, conclusive diagnosis is possible only by kidney biopsy. We aimed to study the potential use of urine cytology in the differential diagnosis between ATN and proliferative glomerular lesion in patients with NS. RESULTS: Cell size analysis showed a higher proportion of small cells and a lower proportion of large cells in the urine of patients with AKI. Cells phenotypes were easily defined using cytological preparations. Leukocytes were found to be a primary classifier of NS groups, with higher number in patients with AKI and patients with proliferative glomerular lesions. Although renal biopsy is still required for confirmative diagnosis, our data suggests that urinary cytology can be readily performed and support the differential diagnosis between proliferative glomerular lesion and ATN in patients with NS and AKI.

Long-term Renal Outcome of Biopsy-proven Acute Tubular Necrosis and Acute Interstitial Nephritis.

BACKGROUND: Although emerging evidence suggest acute kidney injury (AKI) progress to chronic kidney disease (CKD), long-term renal outcome of AKI still remains unclear. Acute tubular necrosis (ATN) is the most common cause of AKI due to ischemia, toxin or sepsis. Acute interstitial nephritis (AIN), caused by drugs or autoimmune diseases is also increasingly recognized as an important cause of AKI. Unlike glomerular diseases, AKI is usually diagnosed in the clinical context without kidney biopsies, and lack of histology might contribute to this uncertainty. METHODS: Among 8,769 biopsy series, 253 adults who were histologically diagnosed with ATN and AIN from 1982 to 2018 at five university hospitals were included. Demographic and pathological features that are associated with the development of end stage renal disease (ESRD) were also examined. RESULTS: Rate of non-recovery of renal function at 6 month was significantly higher in the AIN (ATN vs AIN 49.3 vs 69.4%, P = 0.007) with a 2.71-fold higher risk of non- recovery compared to ATN (95% confidence interval [CI], 1.20-6.47). During the mean follow up of 76.5 ± 91.9 months, ESRD developed in 39.4% of patients with AIN, and 21.5% patients of ATN. The risk of ESRD was significantly higher in AIN (23.05; 95% CI, 2.42-219.53) and also in ATN (12.14; 95% CI, 1.19-24.24) compared to control with non-specific pathology. Older age, female gender, renal function at the time of biopsy and at 6 months, proteinuria and pathological features including interstitial inflammation and fibrosis, tubulitis, vascular lesion were significantly associated with progression to ESRD. CONCLUSION: Our study demonstrated that patients with biopsy proven ATN and AIN are at high risk of developing ESRD. AIN showed higher rate of non-renal recovery at 6 month than ATN.

Histopathological kidney changes and myoglobinuria in neotropical non-human primates attacked by dogs, Brazil.

BACKGROUND: Non-human primates (NHPs) are susceptible to dogs' attacks, events that may cause muscle damage along with stress, and could be in some extent compatible with capture myopathy, a syndrome that results in myoglobinuria and renal damage. METHODS: We aimed to evaluate by histopathology pre-existing lesions and subsequent sequelae related to dogs' attacks, acute tubular necrosis (ATN) and myoglobinuria, as well as the usefulness of Pearls Stain and IHC to diagnose it. Histopathology was performed in available organs, and sections of kidney submitted to Prussian blue stain and myoglobin immunohistochemistry. RESULTS: During January 2014-June 2016, 16/145 (11%) of NHPs received by Adolfo Lutz Institute, Brazil were reported as attacked by dogs. A high frequency of young and debilitated animals was found. Myoglobinuria was observed in more than half animals (9/16; 56.2%), from which (5/9; 55.5%) presented ATN. CONCLUSIONS: Kidney lesions are plausible findings in NHPs attacked by dogs.

Acute kidney injury as the presenting complaint of ceftazidime-induced immune-mediated haemolysis.

We present the case of ceftazidime-induced immune-mediated haemolysis with associated acute kidney injury in a 43-year-old woman. The patient initially presented to the regional cystic fibrosis centre for treatment of an infective exacerbation of cystic fibrosis. After initiation of ceftazidime (a third-generation cephalosporin), renal function rapidly deteriorated and a fall in haemoglobin was noted. On transfer to our care, a haemolysis screen identified immune-mediated haemolysis, and renal biopsy confirmed the finding of acute tubular necrosis secondary to haem pigment. The patient's renal function deteriorated such that she required haemodialysis, although she subsequently recovered and is now dialysis-independent. Although acute haemolytic reactions are recognised with third-generation cephalosporins, this is the first reported case of ceftazidime-induced immune-mediated haemolysis with acute kidney injury. Given the increased frequency of cephalosporin usage, it is important for both nephrologists and general physicians to be aware of this rare but very serious complication.

Risk of Ischemic Kidney Injury in Patients With Nonarteritic Anterior Ischemic Optic Neuropathy: A Nationwide Population-based Study.

PURPOSE: To investigate the risk of acute tubular necrosis (ATN) in patients with nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Population-based cohort study. METHODS: This is a nationwide, population-based, retrospective study using data from the Korean national health claims database from 2011 through 2015. Patients with NAION and randomly selected control subjects from the entire population of South Korea were enrolled. A log-rank analysis was used to evaluate a risk of ATN in the group of patients with NAION (study group) compared to an age-, sex-, and comorbidities-matched control group. Comorbidities included diabetes, chronic lung disease, congestive heart failure, ischemic stroke, anemia, septic shock, and antibiotic use. A Cox proportional hazards regression analysis with cluster effect was performed to calculate the adjusted hazard ratio (aHR) of ATN. RESULTS: A total of 22 498 patients were included in the study group and 31 475 in the control group. Twenty-six cases of ATN were observed in the NAION group and 11 in the control group. The study group was more likely to have ATN (aHR = 2.55, 95% confidence interval: 1.50-5.91, P = .029) than the control group. Among the 26 newly developed cases of ATN, 13 (50%) occurred in the 0-6 months before/after NAION. CONCLUSIONS: We demonstrated that subjects with NAION are at increased risk of ATN and suggested a possible common mechanistic link between the 2 diseases. These results provide significant evidence that proper patient education and further systemic evaluation of the possibility of ATN development are required in patients with NAION.

Diagnóstico de necrosis tubular aguda en pacientes egresados fallecidos / Diagnosis of acute tubular necrosis in deceased patients

Introducción: el diagnóstico histopatológico de necrosis tubular aguda, generalmente de causa isquémica o nefrotóxica, se encuentra muy relacionado con el desarrollo de insuficiencia renal aguda. Objetivo: analizar la presencia de diagnóstico histopatológico de necrosis tubular aguda en los egresados fallecidos autopsiados y explorar la relación con posibles factores favorecedores. Métodos: estudio retrospectivo, observacional de las autopsias en el Hospital Militar Central Dr. Luis Díaz Soto, en el período 1962 al 2015. Se estableció en ellas el diagnóstico histopatológico de necrosis tubular aguda y se analizó el comportamiento de variables demográficas, clínicas y anatomopatológicas. Resultados: se registraron 843 341 egresados, de ellos 25 213 fallecidos (índice de mortalidad 3,0), se realizaron 18 630 autopsias (índice autopsia 75,3 por ciento), en estas se estableció diagnóstico de necrosis tubular aguda en 6.264 (33,6 por ciento). Predominaron los pacientes masculinos y los mayores de 45 años de edad. El shock (22,3 por ciento), la bronconeumonía (16,3 por ciento), la aterosclerosis coronaria(18,5 por ciento) y el edema pulmonar (11,3 por ciento) constituyeron las principales causas directas de muerte. La aterosclerosis coronaria (18,5 por ciento) fue la principal causa básica de muerte. Conclusiones: se registró un incremento sostenido de egresos, de fallecidos y de autopsias practicadas, así como del diagnóstico histopatológico de necrosis tubular aguda. Predominaron los pacientes del sexo masculino y aquellos mayores de 45 años de edad. Las principales causas directas de muerte en estos fueron el shock, la bronconeumonía y el edema pulmonar. La aterosclerosis fue la principal causa básica de muerte(AU)

Introduction: The histopathological diagnosis of acute tubular necrosis, usually of ischemic or nephrotoxic cause, is closely related to the development of acute renal failure. Objective: To analyze the presence of histopathological diganosis of acute tubular necrosis in deceased autopsied and to explore the relationship with possible favoring factors. Method: Retrospective, observational study, with descriptive statistical study of the autopsies at the Central Military Hospital Dr. Luis Díaz Soto in the period from 1962 to 2015. The histopathological diagnosis of acute tubular necrosis was done and demographic, clinical and anatomopathological variables were analyzed. Results: 843 341 discharged from hospital were recorded, of which 25 213 died (mortality rate 3.0), 18 630 autopsies were performed (autopsy rate 75.3 percent). In these cases a diagnosis of acute tubular necrosis was done in 6 264 (33.6 percent). Male patients and those over 45 years of age predominated. Shock (22.3 percent), bronchopneumonia (16.3 percent), coronary atherosclerosis (18.5 percent) and pulmonary edema (11.3 percent) were the main direct causes of death. Coronary atherosclerosis (18.5 percent) was the main underlying cause of death. Conclusions: There was a sustained increase in discharged patients, deaths and autopsies, as well as the histopathological diagnosis of acute tubular necrosis. Male patients predominated and those older than 45 years of age. The main direct causes of death in these were shock, bronchopneumonia and pulmonary edema. Atherosclerosis was the leading cause of death(AU)

Rhabdomyolysis with acute tubular necrosis following occupational inhalation of thinners.

Thinners are mixtures of organic solvents commonly containing toluene, xylene, acetone, hexane, benzene and methyl isobutyl ketone. This report describes a case of rhabdomyolysis with acute tubular necrosis and renal failure, most likely attributable to toluene, following occupational exposure to thinners while cleaning a steel water tank. These adverse health effects have previously been reported following acute poisoning or intentional inhalation by drug abusers, but rarely in the occupational setting. Poor working conditions, lack of health and safety training and delayed treatment contributed to the onset and severity of the patient's complications. This case emphasizes the need for strict control measures, including adequate ventilation, training on working in confined spaces, appropriate personal protective equipment and emergency rescue procedures in such settings. In addition, rhabdomyolysis, acute tubular necrosis and renal failure should be added to safety data material as possible complications of excessive inhalation of thinners.

Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease.

Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13-71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.

Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Acute kidney injury (AKI) is a common complication in patients with cirrhosis that increases mortality. The most common causes of AKI in these patients are prerenal azotemia, acute tubular necrosis (ATN), and hepatorenal syndrome; it is important to determine the etiology of AKI to select the proper treatment and predict patient outcome. Urine biomarkers could be used to differentiate between patients with ATN and functional causes of AKI. We performed a systematic review and meta-analysis of published studies to determine whether urine levels of interleukin (IL)18 and lipocalin 2 or neutrophil gelatinase-associated lipocalin (NGAL) are associated with the development of ATN in patients with cirrhosis. METHODS: We searched MEDLINE, Scopus, ISI Web of Knowledge, and conference abstracts through December 31, 2015, for studies that assessed urine biomarkers for detection of acute kidney injury in patients with cirrhosis or reported an association between urine biomarkers and all-cause mortality in these patients. We included only biomarkers assessed in 3 or more independent studies, searching for terms that included urine biomarkers, cirrhosis, NGAL, and IL18. We calculated the pooled sensitivities and specificities for detection and calculated the area under the receiver operating characteristic curve (AUC) values using a bivariate logistic mixed-effects model. We used the χ2 test to assess heterogeneity among studies. RESULTS: We analyzed data from 8 prospective studies, comprising 1129 patients with cirrhosis. We found urine levels of the markers discriminated between patients with ATN and other types of kidney impairments, with AUC values of 0.88 for IL18 (95% confidence interval [CI], 0.79-0.97) and 0.89 for NGAL (95% CI, 0.84-0.94). Urine levels of IL18 identified patients who would die in the hospital or within 90 days (short-term mortality) with an AUC value of 0.76 (95% CI, 0.68-0.85); NGAL identified these patients with the same AUC (0.76; 95% CI, 0.71-0.82). CONCLUSIONS: In a systematic review and meta-analysis, we found that urine levels of IL18 and NGAL from patients with cirrhosis discriminate between those with ATN and other types of kidney impairments, with AUC values of 0.88 and 0.89, respectively. Urine levels of IL18 and NGAL identified patients with short-term mortality with an AUC value of 0.76. These biomarkers might be used to determine prognosis and select treatments for patients with cirrhosis.

Acute tubular necrosis following transurethral resection of the Prostate using Glycine as irrigating fluid.

Transurethral resection of the prostate is currently the gold standard for the surgical treatment of the benign prostatic hyperplasia. This surgery may lead transurethral resection of the prostate (TURP) syndrome and in some cases, acute tubular necrosis can develop. We report a patient who developed hyponatremia, hemolysis and oliguric acute renal failure as a major complication following TURP using glycine as irrigating fluid.A 64-year-old man was admitted for a prostate resection procedure. Physical examination revealed a healthy elderly man. Preoperative laboratory data showed serum sodium 140 mEq/L, blood urea nitrogen (BUN) 0.6 g/L, creatinine 0.7 mg/dL and hemoglobin 12.9 g/dL. Few hours after, the patient becomes incoherent and developed oliguria, nausea and vomiting. The laboratory data revealed rapidly elevating BUN and creatinine levels (BUN 2.4 g/L; creatinine 6.1 mg/dL), the serum sodium concentration decreased by 14 meq/L. A decreased hemoglobin level (7.4 g/dL) with an elevated lactate dehydrogenase level (665 U/L) was observed. Renal ultrasonography was normal. The diagnosis of acute tubular necrosis complicating TURP syndrome was retained. The hyponatremia was slowly corrected to 132 mmol/L by diuresis and fluid restriction. The renal function recovered after four hemodialysis sessions. Using glycine as an irrigant for TURP may cause hyponatremia, hemolysis and also acute renal failure, especially in patients with longer resection time. It is necessary to carry out every effort to shorten resection time and avoid extravasation during surgery.

Marcadores biológicos para necrose tubular aguda em pacientes com doença glomerular / Biological markers for acute tubular necrosis in patients with glomerular disease

INTRODUCTION: Acute kidney injury (AKI) is a common complication in patients with nephrotic syndrome (NS), and it is reported in 34% of adults with idiopathic nephrotic syndrome. Emergence of AKI in the course of nephrotic syndrome requires a prompt differential diagnosis between acute tubular necrosis (ATN) and proliferative glomerular lesions leading to rapidly progressive glomerulonephritis. Although clinical and conventional laboratory clues can be decisive in many cases, sometimes such distinctions rely on renal biopsy, which is an invasive procedure and is not available in many centers. Several new biomarkers have emerged, increasing the perspective on early diagnosis and the prognostic prediction of AKI. OBJECTIVES: In this work, we studied the use of tests based on the urinary concentrations of kidney injury molecule-1 (KIM-1)...

INTRODUÇÃO: A lesão renal aguda (LRA) é uma complicação frequente em pacientes com glomerulopatias, acomentendo até 34% dos adultos com síndrome nefrótica (SNO) idiopática. O diagnóstico diferencial de necrose tubular aguda (NTA) de glomeulonefrite proliferativa ou crescêntica em pacientes com SNO e LRA é fundamental, visto que a NTA pode mimetizar quadro de glomerulonefrite rapidamente progressiva. Dados clínicos e laboratoriais podem ser úteis no diagnóstico diferencial da LRA na SNO, entretanto a distinção entre NTA e glomerulonefrite proliferativa ou crescêntica é feito pela biópsia renal, procedimento invasivo e que não está disponível amplamente. Novos biomarcadores para diagnóstico precoce e preditores diagnósticos na LRA têm sido identificados. OBJETIVOS: Neste trabalho nós avaliamos o uso de testes baseados nas concentrações urinárias de kidney injury molecule-1 (KIM-1)...