SAMBA: Structure-Learning of Aquaculture Microbiomes Using a Bayesian Approach.

Gut microbiomes of fish species consist of thousands of bacterial taxa that interact among each other, their environment, and the host. These complex networks of interactions are regulated by a diverse range of factors, yet little is known about the hierarchy of these interactions. Here, we introduce SAMBA (Structure-Learning of Aquaculture Microbiomes using a Bayesian Approach), a computational tool that uses a unified Bayesian network approach to model the network structure of fish gut microbiomes and their interactions with biotic and abiotic variables associated with typical aquaculture systems. SAMBA accepts input data on microbial abundance from 16S rRNA amplicons as well as continuous and categorical information from distinct farming conditions. From this, SAMBA can create and train a network model scenario that can be used to (i) infer information of how specific farming conditions influence the diversity of the gut microbiome or pan-microbiome, and (ii) predict how the diversity and functional profile of that microbiome would change under other variable conditions. SAMBA also allows the user to visualize, manage, edit, and export the acyclic graph of the modelled network. Our study presents examples and test results of Bayesian network scenarios created by SAMBA using data from a microbial synthetic community, and the pan-microbiome of gilthead sea bream (Sparus aurata) in different feeding trials. It is worth noting that the usage of SAMBA is not limited to aquaculture systems as it can be used for modelling microbiome-host network relationships of any vertebrate organism, including humans, in any system and/or ecosystem.

On the Compatibility of Fish Meal Replacements in Aquafeeds for Rainbow Trout. A Combined Metabolomic, Proteomic and Histological Study.

The sustainable development of modern aquaculture must rely on a significant reduction of the fish meal (FM) used in aquafeed formulations. However, FM substitution with alternative ingredients in diets for carnivorous fish species often showed reduced nutrient absorption, significantly perturbed metabolisms, and histological changes at both hepatic and intestinal levels. In the present study, rainbow trout (Oncorhynchus mykiss) were fed three different experimental aquafeeds. A control diet with higher FM content (27.3%) than two test formulations in which FM was substituted with two more sustainable and promising alternatives: insect meal (Hermetia illucens larvae = 10.1%, FM = 11.6%) and poultry by-products meal (PBM = 14.8%; FM = 11.7%). Combined metabolomics and proteomics analyses of fish liver, together with histological examination of liver and intestine demonstrated that a well-balanced formulation of nutrients in the three diets allowed high metabolic compatibility of either substitution, paving the way for a deeper understanding of the impact of novel raw materials for the fish feed industry. Results show that the main metabolic pathways of nutrient absorption and catabolism were essentially unaltered by alternative feed ingredients, and also histological alterations were negligible. It is demonstrated that the substitution of FM with sustainable alternatives does not have a negative impact on fish metabolism, as long as the nutritional requirements of rainbow trout are fulfilled.

Impact of polypropylene microplastics and chemical pollutants on European sea bass (Dicentrarchus labrax) gut microbiota and health.

Plastic pollution has become a global problem for marine ecosystems. Microplastics (MPs) are consumed by several marine organisms, including benthic and pelagic fish species that confuse them with food sources, thus contributing to bioaccumulation along the food chain. In addition to structural intestinal damage, ingestion of MPs represents a pathway for fish exposure to potentially hazardous chemicals, too. Most of them are endocrine disrupters, genotoxic or induce immune depression in fish. Accordingly, we assessed the combined toxicological effects of microplastics (MPs) and adsorbed pollutants by adding them to marine fish diet. European sea bass (Dicentrarchus labrax) juveniles were fed for 60 days with feeds containing polypropylene MPs, either virgin or contaminated with chemical pollutants (a blend of dichlorodiphenyldichloroethylene, chlorpyrifos, and benzophenone-3). The data demonstrated a synergic action of MPs and chemical pollutants to induce an inflammatory-like response in distal intestine of sea bass as shown by the up regulation of cytokine il-6 and tnf-α expression. Morphological analysis detected the presence of a focus of lymphocytes in anterior and posterior intestinal segments of fish fed with contaminants in the diet. With regard to microbiota, significant changes in bacterial species richness, beta diversity, and composition of gut microbiota were observed as a consequence of both pollutants and polluted MPs ingestion. These perturbations in gut microbial communities, including the reduction of beneficial lactic acid bacteria and the increase in potential pathogenic microorganism (Proteobacteria and Vibrionales), were undeniable signs of intestinal dysbiosis, which in turn confirmed the signs of inflammation caused by pollutants, especially when combined with MPs. The results obtained in this study provide, therefore, new insights into the potential risks of ingesting MPs as pollutant carriers in marine fish.

Effect of partial substitution of fishmeal with insect meal (Hermetia illucens) on gut neuromuscular function in Gilthead sea bream (Sparus aurata).

Alternative nutrient sources to fishmeal for fish feed, such as insect meals, represent a promising sustainable supply. However, the consequences for fish digestive function have not been exhaustively investigated. In the present study we evaluated the effect of partial fishmeal substitution with 10% Hermetia illucens (Hi10) larvae meal on the neuromuscular function of proximal and distal intestine in gilthead sea bream. In animals fed with insect meal, weight and growth parameters were similar to controls fed with conventional fishmeal. In addition, no anomalies in intestinal gross morphology and no overt signs of inflammation were observed. The gastrointestinal transit was significantly reduced in Hi10 fed animals. In the proximal and distal intestine longitudinal muscle, Hi10 feeding downregulated the excitatory cholinergic and serotoninergic transmission. Sodium nitroprusside-induced inhibitory relaxations increased in the proximal intestine and decreased in the distal intestine after Hi10 meal. Changes in the excitatory and inhibitory components of peristalsis were associated with adaptive changes in the chemical coding of both proximal and distal intestine myenteric plexus. However, these neuromuscular function alterations were not associated with considerable variations in morphometric growth parameters, suggesting that 10% Hi meal may represent a tolerable alternative protein source for gilthead sea bream diets.

Effects of full replacement of dietary fishmeal with insect meal from Tenebrio molitor on rainbow trout gut and skin microbiota.

BACKGROUND: Aquaculture must continue to reduce dependence on fishmeal (FM) and fishoil in feeds to ensure sustainable sector growth. Therefore, the use of novel aquaculture feed ingredients is growing. In this regard, insects can represent a new world of sustainable and protein-rich ingredients for farmed fish feeds. Accordingly, we investigated the effects of full replacement of FM with Tenebrio molitor (TM) larvae meal in the diet of rainbow trout (Oncorhynchus mykiss) on fish gut and skin microbiota. METHODS: A feeding trial was conducted with 126 trout of about 80 g mean initial weight that were fed for 22 weeks with two isonitrogenous, isolipidic, and isoenergetic extruded experimental diets. Partially defatted TM meal was included in one of the diets to replace 100% (TM 100) of FM, whereas the other diet (TM 0) was without TM. To analyse the microbial communities, the Illumina MiSeq platform for sequencing of 16S rRNA gene and Qiime pipeline were used to identify bacteria in the gut and skin mucosa, and in the diets. RESULTS: The data showed no major effects of full FM substitution with TM meal on bacterial species richness and diversity in both, gut mucosa- and skin mucus-associated microbiome. Skin microbiome was dominated by phylum Proteobacteria and especially by Gammaproteobacteria class that constituted approximately half of the bacterial taxa found. The two dietary fish groups did not display distinctive features, except for a decrease in the relative abundance of Deefgea genus (family Neisseriaceae) in trout fed with insect meal. The metagenomic analysis of the gut mucosa indicated that Tenericutes was the most abundant phylum, regardless of the diet. Specifically, within this phylum, the Mollicutes, mainly represented by Mycoplasmataceae family, were the dominant class. However, we observed only a weak dietary modulation of intestinal bacterial communities. The only changes due to full FM replacement with TM meal were a decreased number of Proteobacteria and a reduced number of taxa assigned to Ruminococcaceae and Neisseriaceae families. CONCLUSIONS: The data demonstrated that TM larvae meal is a valid alternative animal protein to replace FM in the aquafeeds. Only slight gut and skin microbiota changes occurred in rainbow trout after total FM replacement with insect meal. The mapping of the trout skin microbiota represents a novel contribution of the present study. Indeed, in contrast to the increasing knowledge on gut microbiota, the skin microbiota of major farmed fish species remains largely unmapped but it deserves thorough consideration.

Intestinal microbial communities of rainbow trout (Oncorhynchus mykiss) may be improved by feeding a Hermetia illucens meal/low-fishmeal diet.

With demands and reliance on aquaculture still growing, there are various challenges to allow sustainable growth and the shift from fishmeal (FM) to other protein sources in aquafeed formulations is one of the most important. In this regard, interest in the use of insect meal (IM) in aquafeeds has grown rapidly. Accordingly, the aim of the present study was to assess the effects of dietary IM from Hermetia illucens (Hi) larvae included in a low-FM diet on gut microbial communities of rainbow trout (Oncorhynchus mykiss), in terms of both composition and function of microbiome. A feeding trial was conducted using 192 trout of about 100-g mean initial weight. Fish were fed in quadruplicate (4 tanks/diet) for 131 days with two diets: the control (Ctrl) contained 20% of FM as well as other protein sources, whereas the Hi diet contained 15% of Hi larvae meal to replace 50% of the FM contained in the Ctrl diet. High-throughput sequencing of 16S rRNA gene was used to identify the major feed and gut bacterial taxa, whereas Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis was performed on gut bacterial genomes to identify the major active biological pathways. The inclusion of IM led to an increase in Firmicutes, mainly represented by Bacilli class and to a drastic reduction of Proteobacteria. Beneficial genera, such as Lactobacillus and Bacillus, were enriched in the gut of fish fed with the Hi diet, whereas the number of bacteria assigned to the pathogenic Aeromonas genus was drastically reduced in the same fish group. The metagenome functional data provided evidence that dietary IM inclusion can shape the metabolic activity of trout gut microbiota. In particular, intestinal microbiome of fish fed with IM may have the capacity to improve dietary carbohydrate utilization. Therefore, H. illucens meal is a promising protein source for trout nutrition, able to modulate gut microbial community by increasing the abundance of some bacteria taxa that are likely to play a key role in fish health.

Management of oral anticoagulation in very old patients with non valvular atrial fibrillation related acute ischemic stroke.

The optimal management of oral anticoagulation (OAC) in the acute phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains controversial, especially in very old patients. Therefore, the aim of our study was to evaluate the practical management of OAC in this context. We conducted an observational retrospective study on patients 85-years old and older admitted to two Italian hospitals for NVAF-related AIS. For each patient, clinical and brain computed tomography data were recorded. Type of OAC (vitamin K antagonists, VKAs or Direct Oral Anticoagulants, DOACs), dosage and starting day after AIS were registered. For each patient 90-day all cause mortality, stroke recurrence, any bleeding and modified Rankin scale (mRS) were reported. One-hundred-seventeen patients, with mean age 89.2 ± 3.4 years, were enrolled. In-hospital and 90-day mortality (out of 109 patients) were 6% and 19.7%, respectively. OAC was started in 93 patients (80.5%), on average after 6 ± 3 days from the acute event. Of them, 88 patients (94.6%) received DOACs, while 5 (5.4%) received VKAs. Patients receiving OAC were significantly younger and suffering from less severe stroke compared with patients who did not receive OAC. Patients receiving OAC presented a reduced in-hospital (2.2% vs. 20.8%, p < 0.004) and 90-day all-cause mortality (9.4% vs. 62.5%, p < 0.001). In patients receiving DOACs, low dosages were used in 87.5% of patients. The use of OAC was not associated with an increased rate of hemorrhagic transformation (HT) during hospitalization (13.2% vs. 9.5%, p = 0.54) or any bleeding at 90-day follow-up. Severe dysphagia and mRS ≥ 4 were found to be independent risk factors for not prescribing OAC. The optimal management of OAC in very old patients suffering from NVAF-related AIS remains a dilemma. In our real world study the majority of patients received OAC as secondary prevention treatment without increase in bleeding risk. Dysphagia and severe disability were independent factors for not prescribing OAC. Further investigations aimed at identifying the optimal approach to OAC during the acute phase of NVAF-related ischemic stroke in this subgroup of patients are warranted.

Direct Oral Anticoagulants in Patients Undergoing Urgent Reperfusion for Nonvalvular Atrial Fibrillation-Related Ischemic Stroke: A Brief Report on Literature Evidence.

INTRODUCTION: The optimal timing for starting anticoagulation in the early phase of nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains a challenge, especially in patients undergoing urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. The aim of our study was to review the literature evidence reporting on safety of direct oral anticoagulants (DOACs) starting in the early phase of NVAF-related AIS undergoing systemic thrombolysis and/or mechanical thrombectomy. MATERIALS AND METHODS: We reviewed the PubMed databases searching articles reporting on efficacy and safety of DOACs starting time within two weeks from AIS onset in patients undergoing systemic thrombolysis and/or mechanical thrombectomy. RESULTS: Three studies were selected, overall including one hundred and six patients (62 females, 58.4%). Median National Institute of Health Stroke Scale (NIHSS) score at hospital admission ranged from 9 to 13 points. Median DOACs starting time ranged from 2 to 6 days. Median CHA2DS2-VASC score ranged from 4 to 6 points. Follow-up was limited to 14 days in one study, 30 days in another, and 90 days in a third one. Overall, stroke recurrence and/or intracranial bleeding occurred in two patients (1.9%) and no patient died at follow-up. CONCLUSION: Small sample size real life studies seem to demonstrate that the introduction of DOACs in the early phase of NVAF-related AIS undergoing urgent reperfusion is efficacious and safe. Prospective RCTs are necessary to confirm these findings.

Direct oral anticoagulants in the early phase of non valvular atrial fibrillation-related acute ischemic stroke: focus on real life studies.

Strong evidence for the use of direct oral anticoagulants (DOACs) in the early phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is lacking, because this kind of patients were excluded from phase III randomized clinical trials (RCT) and ad hoc RCTs are ongoing. In the latest years a lot of real life studies on this topic have been published. The aim of our review was to focus on these. We reviewed the PubMed databases searching articles reporting on DOACs starting time within 2 weeks from AIS onset. We selected fifteen studies, eight with retrospective, six with prospective observational and one with a prospective, open-label, single arm design. Overall, 2920 patients (47.8% females) were included. In twelve studies median or mean age of patients was over 75 years. Mean or median NIHSS ad hospital admission was ≤ 12 in all studies. About one-third of patients (32.4%) received urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. About one-fifth of patients (22.8%) had large infarct size. Median starting time of DOACs was reported in thirteen studies and it ranged from 2 to 8 days. About one-half of patients (45.9%) received a low dose of DOACs. In studies reporting on median or mean CHA2DS2-VASC score, it was ≥ 3 in all. In studies reporting on median or mean HAS-BLED score, it was ≥ 2 in all. Ninety-day follow-up was available for nine studies, overall including about 2200 patients. Incidence of 90-day TIA/stroke recurrence, symptomatic haemorrhagic transformation or intracranial bleeding and all cause mortality was 2.25%, 0.90% and 1.5%, respectively. The real life evidence suggests that early starting of DOACs in patients with NVAF-related AIS is safe and associated with low recurrence risk and all-cause mortality.

Confidence in the Use of Direct Oral Anticoagulants in the Acute Phase of Nonvalvular Atrial Fibrillation-Related Ischemic Stroke Over the Years: A Real-World Single-Center Study.

BACKGROUD AND AIM: The use of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is controversial. The aims of our study were to analyze physicians' confidence in prescribing DOACs in NVAF-related AIS, the characteristics of patients receiving DOACs, and their 90-day prognosis. MATERIAL AND METHODS: Clinical records of consecutive patients admitted to our wards for NVAF-related AIS over the years 2014-2016 were reviewed. RESULTS: One hundred forty-seven patients, 72.7% females, mean age ± standard deviation 83.4 ± 8.8 years, were admitted to our ward for atrial fibrillation (AF)-related AIS (38 in 2014, 47 in 2015, 62 in 2016). Of these patients, 141 had NVAF-related AIS. Median length of hospital stay was 8 days (interquartile range [IQR], 6-11). In-hospital mortality was 10.8%. Ninety-eight patients (69.5%) received DOACs for secondary prevention, with increasing percentages from 2014 (62.5%) to 2016 (88%). In 88% of them, DOACs were started during hospital stay, whereas in 12% DOACs were started during ambulatory follow-up. The median time for starting DOACs was 5 days (IQR, 3-8). In patients receiving DOACs, the median National Institutes of Health Stroke Scale score was 6 (IQR, 3-12), and large ischemic lesions were present in 48%; the median modified Rankin Scale score at hospital discharge was 3 (IQR, 1-4), whereas the score at 90 days was 2 (IQR, 1-3). At the 90-day follow-up, in patients receiving DOACs, overall mortality was 3.0%, stroke recurrence was 1%, and no patients had major intracranial or extracranial bleedings. CONCLUSION: Our study suggests that physicians are becoming increasingly confident in the use of DOACs in NVAF-related AIS. The use of DOACs seems effective and safe even when started in the acute phase of stroke.

Urgent carotid duplex and head computed tomography versus ABCD2 score for risk stratification of patients with transient ischemic attack.

OBJECTIVES: The aim of the study was to prospectively compare the prognostic value of ABCD score, urgent carotid ultrasound (CUS), and unenhanced head computed tomography (UHCT) in patients presenting to the emergency department with transient ischemic attack (TIA). PATIENTS AND METHODS: We carried out a prospective observational study including consecutive adult patients with TIA. Each patient underwent ABCD score assessment, urgent CUS, and UHCT within 24 h from presentation. The primary outcome was the occurrence of ischemic stroke within 30 days. RESULTS: We included 186 patients with a median age of 75 years and a prevalent male sex (57.5%). During follow-up, 12 ischemic strokes (6.5%) occurred, four (7.1%) in patients with ABCD score less than 4 and 8 (6.2%) in those with a score of at least 4. An internal carotid stenosis of at least 50% consistent with the neurological deficit was found in 15 patients (8.1%), and it was associated with a high risk for stroke (odds ratio 4.5, 95% confidence interval 1.1-18.8). An acute ischemic lesion consistent with the neurological deficit was revealed by UHCT in 15 patients (8.1%), and it was associated with a trend of increasing stroke risk (odds ratio 2.5, 95% confidence interval 0.5-12.5). Patients without, with at least one, or with both positive imaging tests showed incremental stroke risk at both 7 (2.5, 12.5, and 33%) and 30 days (5, 12.5, and 33%) (P<0.05 for both). CONCLUSION: Simple imaging tests showed added prognostic value to ABCD score in TIA patients. Urgent CUS together with UHCT should be performed in all TIA patients regardless of ABCD score.

Can emergency physicians accurately and reliably assess acute vertigo in the emergency department?

OBJECTIVE: To validate a clinical diagnostic tool, used by emergency physicians (EPs), to diagnose the central cause of patients presenting with vertigo, and to determine interrater reliability of this tool. METHODS: A convenience sample of adult patients presenting to a single academic ED with isolated vertigo (i.e. vertigo without other neurological deficits) was prospectively evaluated with STANDING (SponTAneousNystagmus, Direction, head Impulse test, standiNG) by five trained EPs. The first step focused on the presence of spontaneous nystagmus, the second on the direction of nystagmus, the third on head impulse test and the fourth on gait. The local standard practice, senior audiologist evaluation corroborated by neuroimaging when deemed appropriate, was considered the reference standard. Sensitivity and specificity of STANDING were calculated. On the first 30 patients, inter-observer agreement among EPs was also assessed. RESULTS: Five EPs with limited experience in nystagmus assessment volunteered to participate in the present study enrolling 98 patients. Their average evaluation time was 9.9 ± 2.8 min (range 6-17). Central acute vertigo was suspected in 16 (16.3%) patients. There were 13 true positives, three false positives, 81 true negatives and one false negative, with a high sensitivity (92.9%, 95% CI 70-100%) and specificity (96.4%, 95% CI 93-38%) for central acute vertigo according to senior audiologist evaluation. The Cohen's kappas of the first, second, third and fourth steps of the STANDING were 0.86, 0.93, 0.73 and 0.78, respectively. The whole test showed a good inter-observer agreement (k = 0.76, 95% CI 0.45-1). CONCLUSIONS: In the hands of EPs, STANDING showed a good inter-observer agreement and accuracy validated against the local standard of care.

Prognostic value of ECG among patients with acute pulmonary embolism and normal blood pressure.

OBJECTIVE: To investigate the prognostic value of electrocardiography (ECG) alone or in combination with echocardiography in patients with acute pulmonary embolism and normal blood pressure. METHODS: Consecutive adult patients presenting to the emergency department at Azienda Ospedaliero-Universitaria Careggi with the first episode of pulmonary embolism were included. Patients with systolic blood pressure less than 100 mm Hg were excluded. ECG and echocardiography were performed within 1 hour from diagnosis and evaluated in a blinded fashion. Right ventricular strain was diagnosed in the presence of one or more of the following ECG findings: complete or incomplete right ventricular branch block, S1Q3T3, and negative T wave in V1-V4. The main outcome measurement was clinical deterioration or death during in-hospital stay. The association of variables with the main outcome was evaluated by multivariate Cox survival analysis. RESULTS: A total of 386 patients with proved pulmonary embolism were included in the study; 201 patients (52%) had right ventricular dysfunction according to echocardiography, and 130 patients (34%) showed right ventricular strain. Twenty-three patients (6%) had clinical deterioration or died. At multivariate survival analysis, right ventricular strain was associated with adverse outcome (hazard ratio 2.58; 95% confidence interval, 1.05-6.36) independently of echocardiographic findings. Patients with both right ventricular strain and right ventricular dysfunction (26%) showed an 8-fold elevated risk of adverse outcome (hazard ratio 8.47; 95% confidence interval, 2.43-29.47). CONCLUSION: Right ventricular strain pattern on ECG is associated with adverse short-term outcome and adds incremental prognostic value to echocardiographic evidence of right ventricular dysfunction in patients with acute pulmonary embolism and normal blood pressure.

Hyperglycemia activates JAK2 signaling pathway in human failing myocytes via angiotensin II-mediated oxidative stress.

Hyperglycemia was reported to enhance angiotensin (Ang) II generation in rat cardiomyocytes, and Ang II inhibition reduces cardiovascular morbidity and mortality in diabetic patients. In diabetic patients, the enhanced activation of intracellular pathways related with myocyte hypertrophy and gene expression might enhance the progression of cardiac damage. Therefore, we investigated the effects of glucose on Ang II-mediated activation of Janus-activated kinase (JAK)-2, a tyrosine kinase related with myocyte hypertrophy and cytokine and fibrogenetic growth factor overexpression, in ventricular myocytes isolated from nonfailing human hearts (n = 5) and failing human hearts (n = 8). In nonfailing myocytes, JAK2 phosphorylation was enhanced by Ang II only in the presence of high glucose (25 mmol/l) via Ang II type I (AT1) receptors (+79% vs. normal glucose, P < 0.05). JAK2 activation was prevented by inhibitors of reactive oxygen species (ROS) generation (diphenyleneiodonium [DPI], tiron, and apocynin). In myocytes isolated from failing hearts, JAK2 phosphorylation was enhanced by high glucose alone (+107%, P < 0.05). High glucose-induced JAK2 activation was blunted by both ACE inhibition (100 nmol/l ramipril) and AT1 antagonism (1 mumol/l valsartan), thus revealing that the effects are mediated by autocrine Ang II production. Inhibition of ROS generation also prevented high glucose-induced JAK2 phosphorylation. In conclusion, in human nonfailing myocytes, high glucose allows Ang II to activate JAK2 signaling, whereas in failing myocytes, hyperglycemia alone is able to induce Ang II generation, which in turn activates JAK2 via enhanced oxidative stress.

[Drug-induced nephropathy]. / Le nefropatie da farmaci.

Drug-induced nephropathy is an important cause of renal injury which is reversible when detected early. Unfortunately, the clinical signs may not be apparent in the early phases and the nephropathy may become evident only at an advanced stage with an acute deterioration of the renal functions or chronic renal insufficiency. It is particularly important not only to know the nephrotoxic potential of the different drug groups, but especially to recognize the patient's risk factors that could be modified or that should preclude the use of these drugs. The presence of comorbid conditions such as older age, diabetes mellitus and congestive heart failure significantly influences the patient's ability to recover from the toxic effects. Many drugs can injure the kidneys, but they cause renal injury via only a few common mechanisms. The aim of the present review is to examine the main clinical presentations of drug-induced nephropathy.