Cardiac effects of renal ischemia.

Mortality in acute kidney injury (AKI) remains very high, yet the cause of death is often failure of extrarenal organs. We and others have demonstrated remote organ dysfunction after renal ischemia. The term "cardiorenal syndrome" was first applied to the "cross talk" between the organs by the National Heart, Lung, and Blood Institute of the National Institutes of Health, and the clinical importance is being increasingly appreciated. Nevertheless, more information is needed to effectively address the consequences of renal injury on the heart. Since AKI often occurs in patients with comorbidities, we investigated the effect of renal ischemia in the setting of existing cardiac failure. We hypothesized that the cardiac effects of renal ischemia would be significantly amplified in experimental cardiomyopathy. Male Sprague-Dawley rats with preexisting cardiac and renal injury due to low-dose doxorubicin were subjected to bilateral renal artery occlusion. Cardiac structure and function were examined 2 days after reperfusion. Loss of functional myocardial tissue with decreases in left ventricular pressure, increases in apoptotic cell death, inflammation, and collagen, and greater disruption in ultrastructure with mitochondrial fragmentation were seen in the doxorubicin/ischemia group compared with animals in the groups treated with doxorubicin alone or following ischemia alone. Systemic inflammation and cardiac abnormalities persisted for at least 21 wk. These results suggest that preexisting comorbidities can result in much more severe distant organ effects of acute renal injury. The results of this study are relevant to human AKI.NEW & NOTEWORTHY Acute kidney injury is common, expensive, and deadly, yet morbidity and mortality are often secondary to remote organ dysfunction. We hypothesized that the effects of renal ischemia would be amplified in the setting of comorbidities. Sustained systemic inflammation and loss of functional myocardium with significantly decreased systolic and diastolic function, apoptotic cell death, and increased collagen and inflammatory cells were found in the heart after renal ischemia in the doxorubicin cardiomyopathy model (vs. renal ischemia alone). Understanding the remote effects of renal ischemia has the potential to improve outcomes in acute kidney injury.

Renal, but not platelet or skin, extracellular vesicles decrease oxidative stress, enhance nascent peptide synthesis, and protect from ischemic renal injury.

Acute kidney injury (AKI) is deadly and expensive, and specific, effective therapy remains a large unmet need. We have demonstrated the beneficial effects of transplanted adult tubular cells and extracellular vesicles (EVs; exosomes) derived from those renal cells on experimental ischemic AKI, even when administered after renal failure is established. To further examine the mechanisms of benefit with renal EVs, we tested the hypothesis that EVs from other epithelia or platelets (a rich source of EVs) might be protective, using a well-characterized ischemia-reperfusion model. When given after renal failure was present, renal EVs, but not those from skin or platelets, markedly improved renal function and histology. The differential effects allowed us to examine the mechanisms of benefit with renal EVs. We found significant decreases in oxidative stress postischemia in the renal EV-treated group with preservation of renal superoxide dismutase and catalase as well as increases in anti-inflammatory interleukin-10. In addition, we propose a novel mechanism of benefit: renal EVs enhanced nascent peptide synthesis following hypoxia in cells and in postischemic kidneys. Although EVs have been used therapeutically, these results serve as "proof of principle" to examine the mechanisms of injury and protection.NEW & NOTEWORTHY Acute kidney injury is common and deadly, yet the only approved treatment is dialysis. Thus, a better understanding of injury mechanisms and potential therapies is needed. We found that organ-specific, but not extrarenal, extracellular vesicles improved renal function and structure postischemia when given after renal failure occurred. Oxidative stress was decreased and anti-inflammatory interleukin-10 increased with renal, but not skin or platelet, exosomes. We also propose enhanced nascent peptide synthesis as a novel protective mechanism.

First Constraints on Heavy QCD Axions with a Liquid Argon Time Projection Chamber Using the ArgoNeuT Experiment.

We present the results of a search for heavy QCD axions performed by the ArgoNeuT experiment at Fermilab. We search for heavy axions produced in the NuMI neutrino beam target and absorber decaying into dimuon pairs, which can be identified using the unique capabilities of ArgoNeuT and the MINOS near detector. This decay channel is motivated by a broad class of heavy QCD axion models that address the strong CP and axion quality problems with axion masses above the dimuon threshold. We obtain new constraints at a 95% confidence level for heavy axions in the previously unexplored mass range of 0.2-0.9 GeV, for axion decay constants around tens of TeV.

Role of coagulation in persistent renal ischemia following reperfusion in an animal model.

Ischemic acute kidney injury is common, deadly, and accelerates the progression of chronic kidney disease, yet has no specific therapy. After ischemia, reperfusion is patchy with early and persistent impairment in regional renal blood flow and cellular injury. We tested the hypothesis that intrarenal coagulation results in sustained renal ischemia following reperfusion, using a well-characterized model. Markedly decreased, but heterogeneous, microvascular plasma flow with microthrombi was found postischemia by intravital microscopy. Widespread tissue factor expression and fibrin deposition were also apparent. Clotting was accompanied by complement activation and inflammation. Treatment with exosomes derived from renal tubular cells or with the fibrinolytic urokinase, given 24 h postischemia when renal failure was established, significantly improved microvascular flow, coagulation, serum creatinine, and histological evidence of injury. These data support the hypothesis that intrarenal clotting occurs early and the resultant sustained ischemia is a critical determinant of renal failure following ischemia; they demonstrate that the coagulation abnormalities are amenable to therapy and that therapy results in improvement in both function and postischemic inflammation.NEW & NOTEWORTHY Ischemic renal injury carries very high morbidity and mortality, yet has no specific therapy. We found markedly decreased, heterogeneous microvascular plasma flow, tissue factor induction, fibrin deposition, and microthrombi after renal ischemia-reperfusion using a well-characterized model. Renal exosomes or the fibrinolytic urokinase, administered after renal failure was established, improved microvascular flow, coagulation, renal function, and histology. Data demonstrate that intrarenal clotting results in sustained ischemia amenable to therapy that improves both function and postischemic inflammation.

MicroBooNE and the ν_{e} Interpretation of the MiniBooNE Low-Energy Excess.

A new generation of neutrino experiments is testing the 4.7σ anomalous excess of electronlike events observed in MiniBooNE. This is of huge importance for particle physics, astrophysics, and cosmology, not only because of the potential discovery of physics beyond the standard model, but also because the lessons we will learn about neutrino-nucleus interactions will be crucial for the worldwide neutrino program. MicroBooNE has recently released results that appear to disfavor several explanations of the MiniBooNE anomaly. Here, we show quantitatively that MicroBooNE results, while a promising start, unquestionably do not probe the full parameter space of sterile neutrino models hinted at by MiniBooNE and other data, nor do they probe the ν_{e} interpretation of the MiniBooNE excess in a model-independent way.

New Constraints on Tau-Coupled Heavy Neutral Leptons with Masses m_{N}=280-970 MeV.

A search for heavy neutral leptons has been performed with the ArgoNeuT detector exposed to the NuMI neutrino beam at Fermilab. We search for the decay signature N→νµ^{+}µ^{-}, considering decays occurring both inside ArgoNeuT and in the upstream cavern. In the data, corresponding to an exposure to 1.25×10^{20} POT, zero passing events are observed consistent with the expected background. This measurement leads to a new constraint at 90% confidence level on the mixing angle |U_{τN}|^{2} of tau-coupled Dirac heavy neutral leptons with masses m_{N}=280-970 MeV, assuming |U_{eN}|^{2}=|U_{µN}|^{2}=0.

New opportunities at the next-generation neutrino experiments I: BSM neutrino physics and dark matter.

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.

Preequilibrium Asymmetries in the

The physical properties of neutrons emitted from neutron-induced fission are fundamental to our understanding of nuclear fission. However, while state-of-the-art fission models still incorporate isotropic fission neutron spectra, it is believed that the preequilibrium prefission component of these spectra is strongly anisotropic. The lack of experimental guidance on this feature has not motivated incorporation of anisotropic neutron spectra in fission models, though any significant anisotropy would impact descriptions of a fissioning system. In the present work, an excess of counts at high energies in the fission neutron spectrum of ^{239}Pu is clearly observed and identified as an excess of the preequilibrium prefission distribution above the postfission neutron spectrum. This excess is separated from the underlying postfission neutron spectrum, and its angular distribution is determined as a function in incident neutron energy and outgoing neutron detection angle. Comparison with neutron scattering models provides the first experimental evidence that the preequilibrium angular distribution is uncorrelated with the fission axis. The results presented here also impact the interpretation of several influential prompt fission neutron spectrum measurements.

Renal Tubular Cell-Derived Extracellular Vesicles Accelerate the Recovery of Established Renal Ischemia Reperfusion Injury.

Ischemic renal injury is a complex syndrome; multiple cellular abnormalities cause accelerating cycles of inflammation, cellular damage, and sustained local ischemia. There is no single therapy that effectively resolves the renal damage after ischemia. However, infusions of normal adult rat renal cells have been a successful therapy in several rat renal failure models. The sustained broad renal benefit achieved by relatively few donor cells led to the hypothesis that extracellular vesicles (EV, largely exosomes) derived from these cells are the therapeutic effector in situ We now show that EV from adult rat renal tubular cells significantly improved renal function when administered intravenously 24 and 48 hours after renal ischemia in rats. Additionally, EV treatment significantly improved renal tubular damage, 4-hydroxynanoneal adduct formation, neutrophil infiltration, fibrosis, and microvascular pruning. EV therapy also markedly reduced the large renal transcriptome drift observed after ischemia. These data show the potential utility of EV to limit severe renal ischemic injury after the occurrence.

Comprehensive genomic profiling in diabetic nephropathy reveals the predominance of proinflammatory pathways.

Despite advances in the treatment of diabetic nephropathy (DN), currently available therapies have not prevented the epidemic of progressive chronic kidney disease (CKD). The morbidity of CKD, and the inexorable increase in the prevalence of end-stage renal disease, demands more effective approaches to prevent and treat progressive CKD. We undertook next-generation sequencing in a rat model of diabetic nephropathy to study in depth the pathogenic alterations involved in DN with progressive CKD. We employed the obese, diabetic ZS rat, a model that develops diabetic nephropathy, characterized by progressive CKD, inflammation, and fibrosis, the hallmarks of human disease. We then used RNA-seq to examine the combined effects of renal cells and infiltrating inflammatory cells acting as a pathophysiological unit. The comprehensive systems biology analysis of progressive CKD revealed multiple interactions of altered genes that were integrated into morbid networks. These pathological gene assemblies lead to renal inflammation and promote apoptosis and cell cycle arrest in progressive CKD. Moreover, in what is clearly a major therapeutic challenge, multiple and redundant pathways were found to be linked to renal fibrosis, a major cause of kidney loss. We conclude that systems biology applied to progressive CKD in DN can be used to develop novel therapeutic strategies directed to restore critical anomalies in affected gene networks.

Impaired microvascular circulation in distant organs following renal ischemia.

Mortality in acute kidney injury (AKI) patients remains very high, although very important advances in understanding the pathophysiology and in diagnosis and supportive care have been made. Most commonly, adverse outcomes are related to extra-renal organ dysfunction and failure. We and others have documented inflammation in remote organs as well as microvascular dysfunction in the kidney after renal ischemia. We hypothesized that abnormal microvascular flow in AKI extends to distant organs. To test this hypothesis, we employed intravital multiphoton fluorescence imaging in a well-characterized rat model of renal ischemia/reperfusion. Marked abnormalities in microvascular flow were seen in every organ evaluated, with decreases up to 46% observed 48 hours postischemia (as compared to sham surgery, p = 0.002). Decreased microvascular plasma flow was found in areas of erythrocyte aggregation and leukocyte adherence to endothelia. Intravital microscopy allowed the characterization of the erythrocyte formations as rouleaux that flowed as one-dimensional aggregates. Observed microvascular abnormalities were associated with significantly elevated fibrinogen levels. Plasma flow within capillaries as well as microthrombi, but not adherent leukocytes, were significantly improved by treatment with the platelet aggregation inhibitor dipyridamole. These microvascular defects may, in part, explain known distant organ dysfunction associated with renal ischemia. The results of these studies are relevant to human acute kidney injury.

Development of a scalable image formation pipeline for multiscale gigapixel photography.

We report on the image formation pipeline developed to efficiently form gigapixel-scale imagery generated by the AWARE-2 multiscale camera. The AWARE-2 camera consists of 98 "microcameras" imaging through a shared spherical objective, covering a 120° x 50° field of view with approximately 40 microradian instantaneous field of view (the angular extent of a pixel). The pipeline is scalable, capable of producing imagery ranging in scope from "live" one megapixel views to full resolution gigapixel images. Architectural choices that enable trivially parallelizable algorithms for rapid image formation and on-the-fly microcamera alignment compensation are discussed.

Ultrasound-guided transversus abdominis plane blocks for laparoscopic appendicectomy in children: a prospective randomized trial.

BACKGROUND: The effect of adding transversus abdominis plane (TAP) blocks to local anaesthetic infiltration on morphine consumption and postoperative pain in children undergoing laparoscopic appendicectomy is unknown. METHODS: After random allocation, 93 children aged 7-16 were randomized to receive ultrasound-guided TAP blocks placed before surgery or not (control). All subjects had port sites infiltrated with ropivacaine and were prescribed i.v. patient-controlled analgesia (PCA) with morphine and oral paracetamol for postoperative pain. The primary outcome was the proportion of subjects using >200 µg kg(-1) morphine. Secondary outcomes included PCA morphine use, pain scores, time intervals to the first use of PCA and other analgesics, sedation scores, postoperative nausea or vomiting, and time to hospital discharge. RESULTS: The procedure duration was longer in the TAP group (111 compared with 97 min for controls, P=0.03). The duration in the recovery ward and that of the hospital stay were similar. There was no difference in the proportion of subjects requiring >200 µg kg(-1) of PCA morphine [control 31/45 (69%), TAP 29/42 (69%), P=0.99]. There was no significant difference in PCA morphine use, time intervals to the first use of PCA or other analgesics, or amounts of other analgesics. More patients in the TAP group had complicated appendicitis [TAP 13/42 (31%), control 5/45 (11%), P=0.02]. Pain scores were reduced for the TAP group in the recovery ward only (median score 0 vs 2, 95% confidence interval 0-3, P=0.03). CONCLUSIONS: TAP blocks increased anaesthesia time by 14 min on average but offered no clinically important benefit over local anaesthetic port-site infiltration to paediatric patients undergoing laparoscopic appendicectomy.

The impact of the World Trade Center attack on FDNY firefighter retirement, disabilities, and pension benefits.

BACKGROUND: Our goal was to examine the effect of the World Trade Center (WTC) attack and subsequent New York City Fire Department (FDNY) rescue/recovery activities on firefighter retirements. We also analyzed the financial impact associated with the increased number and proportion of service-connected "accidental" disability retirements on the FDNY pension system. METHODS: A total of 7,763 firefighters retired between 9/11/1994 and 9/10/2008. We compared the total number of retirements and the number and proportion of accidental disability retirements 7 years before and 7 years after the WTC attack. We categorized WTC-related accidental disability retirements by medical cause and worked with the New York City Office of the Actuary to approximate the financial impact by cause. RESULTS: In the 7 years before 9/11 there were 3,261 retirements, 48% (1,571) of which were accidental disability retirements. In the 7 years after 9/11, there were 4,502 retirements, 66% (2,970) were accidental disability retirements, of which 47% (1,402) were associated with WTC-related injuries or illnesses. After 9/11, the increase in accidental disability retirements was, for the most part, due to respiratory-related illnesses. Additional increases were attributed to psychological-related illnesses and musculoskeletal injuries incurred at the WTC site. Pension benefits associated with WTC-related accidental disability retirements have produced an increased financial burden of over $826 million on the FDNY pension system. CONCLUSIONS: The WTC attacks affected the health of the FDNY workforce resulting in more post-9/11 retirements than expected, and a larger proportion of these retirees with accidental disability pensions.

Rapid progression of diabetic nephropathy is linked to inflammation and episodes of acute renal failure.

BACKGROUND/AIMS: Chronic kidney disease (CKD) from diabetic nephropathy is characterized by progressive loss of renal function. The renal decline has been viewed as a linear fall, presumably dependent on metabolic, hemodynamic and dietary stresses. However, renal injury in diabetic nephropathy can be rapidly aggravated by unpredictable external and internal factors, a state of affairs inconsistent with a linear loss of function. Acute renal injury and subsequent inflammation are potential factors, and we investigated their presence in renal biopsies from patients with nephropathy. METHODS: In a protocol approved by the Indiana University School of Medicine Institutional Review Board, renal biopsy specimens, estimated GFR, proteinuria and renal survival were examined in patients with diabetic nephropathy. RESULTS: Prominent clusters of inflammatory cells, particularly macrophages, were detected in the renal biopsy specimens. CKD progressed rapidly but not linearly, in that CKD was characterized by a succession of seemingly random episodes of self-limited acute renal failure. Episodes of acute kidney injury were associated with progression to end-stage renal disease. CONCLUSIONS: We propose that diabetic nephropathy is complicated by unpredictable and possibly random episodes of usually self-limited acute renal failure, and by subsequent renal inflammation, which appear to accelerate progression and eventual kidney loss.

Treatment of the post-ischaemic inflammatory syndrome of diabetic nephropathy.

BACKGROUND: Diabetes mellitus and its complications are a public health problem of epidemic proportions. Both diabetes and chronic kidney disease (CKD) increase the risk of acute kidney injury (AKI). Months after a single episode of acute ischaemia to the diabetic kidney, we have found an accelerated progression of nephropathy, with impaired function, severe renal inflammation, microvascular dysfunction, fibrosis and apoptotic cell death. We termed this entity the post-ischaemic inflammatory syndrome. We now test the hypothesis that blocking inflammation ameliorates the post-ischaemic inflammatory syndrome. METHODS: Obese-diabetic ZS rats (F(1) hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were treated with mycophenolate mofetil (MMF), subjected to renal ischaemia or sham surgery, and monitored via the powerful technique of intravital microscopy. RESULTS: Amelioration of post-ischaemia inflammation with MMF therapy improved long-term renal function, microvascular dysfunction, fibrosis and apoptosis. CONCLUSION: These data support the hypothesis that the post-ischaemic inflammatory syndrome accelerates diabetic CKD, is a critical determinant of injury, and can be successfully treated.

Postischemic inflammatory syndrome: a critical mechanism of progression in diabetic nephropathy.

Diabetes is a major epidemic, and diabetic nephropathy is the most common cause of end-stage renal disease. Two critical components of diabetic nephropathy are persistent inflammation and chronic renal ischemia from widespread vasculopathy. Moreover, acute ischemic renal injury is common in diabetes, potentially causing chronic kidney disease or end-stage renal disease. Accordingly, we tested the hypothesis that acute renal ischemia accelerates nephropathy in diabetes by activating proinflammatory pathways. Lean and obese-diabetic ZS rats (F(1) hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were subjected to bilateral renal ischemia or sham surgery before the onset of proteinuria. The postischemic state in rats with obesity-diabetes was characterized by progressive chronic renal failure, increased proteinuria, and renal expression of proinflammatory mediators. Leukocyte number in obese-diabetic rat kidney was markedly increased for months after ischemia. Intrarenal blood flow velocity was decreased after ischemia in lean control and obese-diabetic rats, although it recovered in lean rats. At 2 mo after ischemia, blood flow velocity decreased further in sham-surgery and postischemia obese-diabetic rats, so that RBC flow velocity was only 39% of control in the obese-diabetic rats after ischemia. In addition, microvascular density remained depressed at 2 mo in kidneys of obese-diabetic rats after ischemia. Abnormal microvascular permeability and increases in interstitial fibrosis and apoptotic renal cell death were also more pronounced after ischemia in obese-diabetic rats. These data support the hypothesis that acute renal ischemia in obesity-diabetes severely aggravates chronic inflammation and vasculopathy, creating a self-perpetuating postischemia inflammatory syndrome, which accelerates renal failure.

Flavoured cigarettes, sensation seeking and adolescents' perceptions of cigarette brands.

OBJECTIVES: This study examined the interactive effects of cigarette package flavour descriptors and sensation seeking on adolescents' brand perceptions. METHODS: High school students (n = 253) were randomly assigned to one of two experimental conditions and sequentially exposed to cigarette package illustrations for three different brands. In the flavour descriptor condition, the packages included a description of the cigarettes as "cherry", while in the traditional descriptor condition the cigarette brands were described with common phrases found on tobacco packages such as "domestic blend." Following exposure to each package participants' hedonic beliefs, brand attitudes and trial intentions were assessed. Sensation seeking was also measured, and participants were categorised as lower or higher sensation seekers. RESULTS: Across hedonic belief, brand attitude and trial intention measures, there were interactions between package descriptor condition and sensation seeking. These interactions revealed that among high (but not low) sensation seekers, exposure to cigarette packages including sweet flavour descriptors led to more favourable brand impressions than did exposure to packages with traditional descriptors. CONCLUSIONS: Among high sensation seeking youths, the appeal of cigarette brands is enhanced through the use of flavours and associated descriptions on product packaging.

Exploring the roles, functions, and background of patient navigators and case managers: A scoping review.

BACKGROUND: Patient navigators and case managers are health care workers who aim to provide individualized assistance to patients facing significant health concerns. Although these roles emerged from distinct historical need, the terms are often used interchangeably in the literature and are described to have overlapping functions. Differences in the way that these roles are conceptualized across countries has led to a lack of clarity regarding the exact functions that each offer to patients, caregivers, and the health care system. OBJECTIVES: To differentiate the functions and backgrounds of patient navigators and case managers across settings and disease contexts. DESIGN: This review was guided based on the PRISMA extension for scoping reviews using a five-step review process: identify the research questions; search and identify relevant studies; select studies based on a priori criterion; chart the data; and collate, summarize and report the results. DATA SOURCES: A search of the literature was undertaken in peer-reviewed databases (Medline, CINAHL, and PubMed) and the grey literature (Google and unpublished articles in online repositories). REVIEW METHODS: Extracted data included information on patient navigators and/or case managers related to their reported background, training, and/or knowledge; roles and/or specific functions; clinical setting; and targeted condition or disease type. RESULTS: The search strategy resulted in 10,523 articles. After applying the eligibility criteria during title and abstract evaluation, 468 full-text articles were reviewed, resulting in a total of 160 articles. Functions of patient navigators and case managers were organized into nine emerging categories: (1) advocacy; (2) care coordination; (3) case monitoring and patient needs assessment; (4) community engagement; (5) education; (6) administration and research activities; (7) psychosocial support; (8) navigation of services; and (9) reduction of barriers. The background and knowledge areas of each role were compared and contrasted, and three categories related to the practice context of each role were identified: (1) typical setting and care trajectory; (2) target patient population; and (3) mode of service delivery. CONCLUSIONS: The current study identified important differences in the functions between patient navigators and case managers. However, there remains significant ambiguity between the functions of these two roles. Standardized definitions detailing scope of practice, and allowing for inherent flexibility across different settings, are needed to improve service delivery.

Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats.

Hypoxic acute kidney injury, a major unresolved problem, initiates, or aggravates, renal functional and structural decline. There is no treatment for hypoxic acute renal injury and its sequelae. We tested the hypothesis that human kidney tubular cells, or their extracellular vesicles (exosomes), prevent renal injury when infused intravenously 24 hours after 50 minutes of bilateral renal ischemia in Nude rats. Cells and their exosomes were from harvested human kidneys declined for transplantation. Injections of either cells or exosomes, given after 24 and 48 hours of reperfusion, preserved renal function and structure in both treatment groups. However, exosomes were superior to cells; and maintained renal vascular and epithelial networks, prevented renal oxidant stress, and apoptosis; and restrained activation of pro-inflammatory and pro-fibrogenic pathways. Exosomes worked in 24 hours, consistent with functional rather than regenerative activity. Comprehensive proteomic analysis identified 6152 renal proteins from all cellular compartments; and 628 were altered by ischemia at all cell levels, while 377 were significantly improved by exosome infusions. We conclude that renal damage from severe ischemia was broad, and human renal exosomes prevented most protein alterations. Thus, exosomes seem to acutely correct a critical and consequential abnormality during reperfusion. In their absence, renal structure and cells transition to a chronic state of fibrosis and extensive renal cell loss.