新型冠状病毒肺炎（COVID-19）是新近发现的乙类传染病，不仅表现为以病毒性肺炎为特征的呼吸系统病变，重症患者还合并肾脏、心脏、血液、神经系统等多系统器官损伤。该病自2019年12月在我国暴发以来，目前已蔓延至全球20多个国家和地区，被世界卫生组织（WHO）定义为国际关注的突发公共卫生事件。COVID-19与传染性重症急性呼吸综合征（severe acute respiratory syndrome，SARS，惯称“非典型肺炎”）和中东呼吸综合征（Middle East respiratory syndrome，MERS）均由冠状病毒感染引起，而急性肾损伤（acute kidney injury, AKI）是其重要的并发症之一，早期积极处理与防治十分重要。中华医学会肾脏病学分会专家组对该病合并AKI的流行病学、临床特点、诊断和治疗进行总结并提出有关建议，希望能引起广大肾科医师重视，不断提高本病的防治水平。

Some patients with COVID-19 pneumonia also present with kidney injury, and autopsy findings of patients who died from the illness sometimes show renal damage. However, little is known about the clinical characteristics of kidney-related complications, including hematuria, proteinuria, and AKI.In this retrospective, single-center study in China, we analyzed data from electronic medical records of 333 hospitalized patients with COVID-19 pneumonia, including information about clinical, laboratory, radiologic, and other characteristics, as well as information about renal outcomes.We found that 251 of the 333 patients (75.4%) had abnormal urine dipstick tests or AKI. Of 198 patients with renal involvement for the median duration of 12 days, 118 (59.6%) experienced remission of pneumonia during this period, and 111 of 162 (68.5%) patients experienced remission of proteinuria. Among 35 patients who developed AKI (with AKI identified by criteria expanded somewhat beyond the 2012 Kidney Disease: Improving Global Outcomes definition), 16 (45.7%) experienced complete recovery of kidney function. We suspect that most AKI cases were intrinsic AKI. Patients with renal involvement had higher overall mortality compared with those without renal involvement (28 of 251 [11.2%] versus one of 82 [1.2%], respectively). Stepwise multivariate binary logistic regression analyses showed that severity of pneumonia was the risk factor most commonly associated with lower odds of proteinuric or hematuric remission and recovery from AKI.Renal abnormalities occurred in the majority of patients with COVID-19 pneumonia. Although proteinuria, hematuria, and AKI often resolved in such patients within 3 weeks after the onset of symptoms, renal complications in COVID-19 were associated with higher mortality.Copyright © 2020 by the American Society of Nephrology.

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2.We performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells.Light microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 m in diameter and had an envelope studded with crown-like, electron-dense spikes. Vacuoles contained double-membrane vesicles suggestive of partially assembled virus.The presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.Copyright © 2020 by the American Society of Nephrology.

Severe acute respiratory syndrome (SARS) was first described during a 2002-2003 global outbreak of severe pneumonia associated with human deaths and person-to-person disease transmission. The etiologic agent was initially identified as a coronavirus by thin-section electron microscopic examination of a virus isolate. Virions were spherical, 78 nm in mean diameter, and composed of a helical nucleocapsid within an envelope with surface projections. We show that infection with the SARS-associated coronavirus resulted in distinct ultrastructural features: double-membrane vesicles, nucleocapsid inclusions, and large granular areas of cytoplasm. These three structures and the coronavirus particles were shown to be positive for viral proteins and RNA by using ultrastructural immunogold and in situ hybridization assays. In addition, ultrastructural examination of a bronchiolar lavage specimen from a SARS patient showed numerous coronavirus-infected cells with features similar to those in infected culture cells. Electron microscopic studies were critical in identifying the etiologic agent of the SARS outbreak and in guiding subsequent laboratory and epidemiologic investigations.

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID‐19‐associated organ alterations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism.In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR.The median age of our cohort was 73·5 years (range 42-84; IQR 67·5-77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue.The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination.None.Copyright © 2020 Elsevier Ltd. All rights reserved.

Coronavirus disease-2019 (COVID-19) is an ongoing pandemic which has affected over 12 million people across the globe. Manifestations in different organs systems are being reported regularly. Renal biopsy findings in hospitalized COVID-19 patients presenting solely with acute kidney injury (AKI) have recently been described in published literature in few case reports. The findings include diffuse acute tubular injury (ATI) along with the glomerular lesion of collapsing glomerulopathy (CG). However, nephrotic syndrome as the presenting complaint of COVID-19 has not been reported widely, neither has any other glomerular lesion other than CG.We describe the kidney biopsy findings of two patients who had recent diagnoses of COVID-19 and presented with new-onset nephrotic syndrome. Renal biopsy in both patients showed ATI (as in previous reports) and distinct glomerular findings on light microscopy - that of minimal change disease (MCD) initially in one patient followed by CG in a subsequent biopsy and CG at the outset in the other patient. The electron microscopic findings in both patients were that of severe podocytopathy (diffuse and severe podocyte foot process effacement).Our cases highlight a novel clinical presentation of COVID-19 renal disease, not described before, that of new-onset nephrotic syndrome. While all published case reports describe CG as the glomerular pathology, we describe a non-CG pathology (MCD) in one of our cases, thereby adding to the repertoire of renal pathology described in association with COVID-19 patients. However, the exact mechanism by which podocyte injury or podocytopathy occurs in all such cases is still unknown. Optimal treatment options for these patients also remains unknown at this time.

Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series.We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients.Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.Copyright © 2020 by the American Society of Nephrology.

Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus. The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin-angotensin-aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions.

Among patients hospitalized for novel coronavirus disease (COVID-19), between 10 and 14% develop an acute kidney injury and around half display marked proteinuria and haematuria. Post-mortem analyses of COVID-19 kidney tissue suggest that renal tubular cells and podocytes are affected. Here we report two cases of collapsing glomerulopathy and tubulointerstitial lesions in living COVID-19 patients. Despite our use of sensitive reverse transcription polymerase chain reaction techniques in this study, we failed to detect the virus in blood, urine and kidney tissues. Our observations suggest that these kidney lesions are probably not due to direct infection of the kidney by severe acute respiratory syndrome coronavirus 2.© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.

We report a case of a kidney transplant recipient who presented with acute kidney injury and nephrotic-range proteinuria in a context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Kidney biopsy revealed collapsing glomerulopathy. Droplet-based digital polymerase chain reaction did not detect the presence of SARS-CoV-2 RNA in the biopsy fragment, and the virus was barely detectable in plasma at the time of the biopsy. SARS-CoV-2 RNAemia peaked several days later, followed by a seroconversion despite the absence of circulating CD19-positive lymphocytes at admission due to rituximab-based treatment of antibody-mediated rejection 3 months earlier. Genotyping for the 2 risk alleles of the apolipoprotein L1 (APOL1) gene revealed that the donor carried the low-risk G0/G2 genotype. This case illustrates that coronavirus disease 2019 infection may promote a collapsing glomerulopathy in kidney allografts with a low-risk APOL1 genotype in the absence of detectable SARS-CoV-2 RNA in the kidney and that podocyte injury may precede SARS-CoV-2 RNAemia.Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Kidney involvement may occur in coronavirus disease 2019 (COVID-19), and can be severe among Black individuals. In this study of collapsing glomerulopathy in six Black patients with COVID-19, the authors found that all six had variants in the gene encoding apo L1 (APOL1) that are more common among those of African descent and linked by past research to susceptibility to collapsing glomerulopathy in non–COVID-19 patients. They found no evidence of direct kidney viral infection but observed changes in gene expression in kidney biopsy samples suggesting that the mechanism is likely driven by a host response. These findings suggest that Black individuals with an APOL1 high-risk genotype and severe acute respiratory syndrome coronavirus 2 infection are at increased risk for experiencing an aggressive form of kidney disease associated with high rates of kidney failure.

Collapsing glomerulopathy may occur in an idiopathic (primary) form and in association with a wide spectrum of infectious and inflammatory conditions and medications. The association of collapsing glomerulopathy with human immunodeficiency virus (HIV)-1 infection is well established; less certain is the association with other viral infections.We searched PubMed for articles in all languages that addressed glomerulopathies associated with parvovirus B19, cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis C virus (HCV) and simian virus 40 (SV40).Case reports and small-case series link infection with these common viruses and glomerular injury. The evidence for a pathogenic role is generally stronger for glomerulonephritis than for collapsing glomerulopathy.The evidence linking collapsing glomerulopathy with CMV is relatively strong but not yet conclusive, while the evidence for a pathogenic role for EBV and parvovirus B19 is weaker.

The striking emergence of an epidemic of HIV-related renal disease in patients with end-stage renal disease provided the rationale for the exploration of whether HIV-1 directly infects renal parenchymal cells. Renal glomerular and tubular epithelial cells contain HIV-1 mRNA and DNA, indicating infection by HIV-1. In addition, circularized viral DNA, a marker of recent nuclear import of full-length, reverse-transcribed RNA, was detected in the biopsies, suggesting active replication in renal tissue. Infiltrating infected leukocytes harbored more viral mRNA than renal epithelium. Identification of this novel reservoir suggests that effectively targeting the kidney with antiretrovirals may be critical for patients who are seropositive with renal disease. Thus, renal epithelium constitutes a unique and previously unrecognized cell target for HIV-1 infection.

Collapsing glomerulopathy (CG), a disorder with severe glomerular and tubular involvement, occurs either as an idiopathic lesion or in some patients with human immunodeficiency virus (HIV) infection known as HIV-associated nephropathy (HIVAN). We previously reported a renal transplant recipient with de novo CG and red cell aplasia in association with persistent parvovirus B19 (PVB19) infection. This prompted us to look for an association between PVB19 infection and CG.DNA from archived biopsies of patients with CG was analyzed for PVB19 by polymerase chain reaction (PCR). Results were compared with HIVAN, idiopathic focal segmental glomerulosclerosis (FSGS), and controls. In situ hybridization (ISH) was done to localize PVB19 in renal biopsies. Peripheral blood specimens of patients with CG, HIV infection, healthy controls, and randomly selected hospitalized patients (sick controls) were also analyzed for PVB19.PVB19 DNA was detected in renal biopsies of 18 out of 23 (78.3%) patients with CG, 3 out of 19 (15.8%) with HIVAN, 6 out of 27 (22.2%) with FSGS, and 7 out of 27 (25.9%) controls (P < 0.01, CG vs. HIVAN, FSGS, and controls). PVB19 was detected in peripheral blood of 7 out of 8 (87.5%) CG patients, 3 out of 22 (13.6%) with HIV infection, 4 out of 133 (3%) healthy controls, and 2 out of 50 (4%) sick controls (P < 0.001, CG vs. HIV infected, healthy, and sick controls). PVB19 was identified in glomerular parietal and visceral epithelial and tubular cells by ISH.The significantly higher prevalence of PVB19 DNA in renal biopsies and peripheral blood of CG patients suggests a specific association between PVB19 infection and CG. In susceptible individuals, renal epithelial cell infection with PVB19 may induce CG.

African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.

COVID-19 associated cytokine storm could rapidly induce ARDS, and the patients would require mechanical ventilation. However, the prognosis was not that optimistic. The outcome might be changed if the timely intervention of EBP was performed. We present a case of severe SARS-CoV-2 infection who recovered from a cytokine storm.Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

This study examined the expression of renal phospholipase A2 receptor (PLA2R) in idiopathic and secondary membranous nephropathy (MN).Patients with biopsy-proven MN and non-MN were enrolled. Renal PLA2R was examined using an anti-PLA2R antibody (anti-PLA2R-Ab), and circulating PLA2R-Ab was detected by indirect immunofluorescence.Renal PLA2R was detected along the capillary loop in 84% patients with idiopathic MN but not in those with any other primary glomerulonephritis. Only 1 of 38 patients with class V lupus nephritis showed renal PLA2R positive. In hepatitis B virus-associated MN (HBV-MN), 64% showed renal PLA2R positive, and PLA2R overlapped with HBsAg along the capillary loop. In addition, renal PLA2R positivity was closely associated with serum PLA2R-Ab. Renal PLA2R positive was present in all the patients with serum PLA2R-Ab positive and in 53% of patients with serum PLA2R-Ab negative. However, in patients with renal PLA2R negative, serum PLA2R-Ab was all negative.Renal biopsy PLA2R positivity was common in idiopathic MN and HBV-MN but rare in lupus-associated MN, and it was closely associated with serum PLA2R-Ab production. Further studies examining the association between PLA2R and HBV-MN may shed light on the mechanism of idiopathic MN or HBV-MN. © 2015 S. Karger AG, Basel.

Reports show that AKI is a common complication of severe coronavirus disease 2019 (COVID-19) in hospitalized patients. Studies have also observed proteinuria and microscopic hematuria in such patients. Although a recent autopsy series of patients who died with severe COVID-19 in China found acute tubular necrosis in the kidney, a few patient reports have also described collapsing glomerulopathy in COVID-19.We evaluated biopsied kidney samples from ten patients at our institution who had COVID-19 and clinical features of AKI, including proteinuria with or without hematuria. We documented clinical features, pathologic findings, and outcomes.Our analysis included ten patients who underwent kidney biopsy (mean age: 65 years); five patients were black, three were Hispanic, and two were white. All patients had proteinuria. Eight patients had severe AKI, necessitating RRT. All biopsy samples showed varying degrees of acute tubular necrosis, and one patient had associated widespread myoglobin casts. In addition, two patients had findings of thrombotic microangiopathy, one had pauci-immune crescentic GN, and another had global as well as segmental glomerulosclerosis with features of healed collapsing glomerulopathy. Interestingly, although the patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RT-PCR, immunohistochemical staining of kidney biopsy samples for SARS-CoV-2 was negative in all ten patients. Also, ultrastructural examination by electron microscopy showed no evidence of viral particles in the biopsy samples.The most common finding in our kidney biopsy samples from ten hospitalized patients with AKI and COVID-19 was acute tubular necrosis. There was no evidence of SARS-CoV-2 in the biopsied kidney tissue.Copyright © 2020 by the American Society of Nephrology.

The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.

A group of pauci-immune vasculitides, characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of antineutrophil cytoplasmic antibodies (ANCAs), is referred to as ANCA-associated vasculitis (AAV). ANCAs against proteinase 3 (PR3) (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) are found in over 90% of patients with active disease, and these ANCAs are implicated in the pathogenesis of AAV. Dying neutrophils surrounding the walls of small vessels are a histological hallmark of AAV. Traditionally, it has been assumed that these neutrophils die by necrosis, but neutrophil extracellular traps (NETs) have recently been visualized at the sites of vasculitic lesions. AAV patients also possess elevated levels of NETs in the circulation. ANCAs are capable of inducing NETosis in neutrophils, and their potential to do so has been shown to be affinity dependent and to correlate with disease activity. Neutrophils from AAV patients are also more prone to release NETs spontaneously than neutrophils from healthy blood donors. NETs contain proinflammatory proteins and are thought to contribute to vessel inflammation directly by damaging endothelial cells and by activating the complement system and indirectly by acting as a link between the innate and adaptive immune system through the generation of PR3-and MPO-ANCA. Injection of NET-loaded myeloid dendritic cells into mice results in circulating PR3-and MPO-ANCA and the development of AAV-like disease. NETs have also been shown to be essential in a rodent model of drug-induced vasculitis. NETs induced by propylthiouracil could not be degraded by DNaseI, implying that disordered NETs might be important for the generation of ANCAs. NET degradation was also highlighted in another study showing that AAV patients have reduced DNaseI activity resulting in less NET degradation. With this in mind, it might be that prolonged exposure to proteins in the NETs due to the overproduction of NETs and/or reduced clearance of NETs is important in AAV. However, not all ANCAs are pathogenic and some might possibly also aid in the clearance of NETs. A dual role for ANCAs in relation to circulating NET levels has been proposed because a negative correlation was observed between PR3-ANCA and NET remnants in patients in remission.

We annotated the top transcripts associated with kidney transplant rejection by p-value, either universal for all rejection or selective for T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR; ClinicalTrials.gov NCT01299168). We used eight class-comparison algorithms to interrogate microarray results from 703 biopsies, 205 with rejection. The positive comparators were all rejection, TCMR, or ABMR; the negative comparators varied from normal biopsies to all nonrejecting biopsies, including other diseases. The universal algorithm, rejection versus all nonrejection, identified transcripts mainly inducible by interferon γ. Selectivity for ABMR or TCMR required the other rejection class as well as nonrejection biopsies in the comparator to avoid selecting universal transcripts. Direct comparison of ABMR versus TCMR yielded only transcripts related to TCMR, the stronger signal. Transcripts highly associated with rejection were never completely specific for rejection: Many were increased in biopsies without rejection, reflecting sharing between rejection and injury-induced innate immunity. Union of the top 200 transcripts from universal and selective algorithms yielded 454 transcripts that permitted unsupervised analysis of biopsies in principal component analysis: PC1 was rejection, and PC2 was separation of TCMR from ABMR. Appreciating rejection-associated molecular changes requires a diverse case mix, accurate histologic classification (including C4d-negative ABMR), and both selective and universal algorithms.© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Renal tissues from two groups of patients with acquired immune deficiency syndrome (AIDS) were examined: Group A had severe proteinuria and varying degrees of renal insufficiency, designated AIDS-associated nephropathy (AAN), and Group B had no renal involvement. Control Group C consisted of patients with heroin-associated nephropathy (HAN) with proteinuria comparable to patients in Group A but without AIDS or its related complex (ARC). The most frequent finding, common to both AAN and HAN, was focal glomerular sclerosis. In contrast to HAN, AAN tissue showed mesangial hypocellularity, sparse interstitial infiltrates, severe tubular degenerative changes, tubular microcystic ectasia, Bowman's space dilatation, and presence of multiple complex inclusions both in the nuclei and cytoplasm in a variety of cells. Abundant tubuloreticular inclusions were found in the endothelial and occasionally in the interstitial cell cytoplasm. Nuclear bodies (NBs) were seen in greater frequency, complexity, size, and heterogeneity, and of budding configuration in Group A as compared with Groups B and C; NBs in Group C were mostly of simple types (I and II). In addition, a peculiar granulofibrillary transformation in many tubular and interstitial cell nuclei was observed in Group A. This transformation was rarely present in Group B and was never seen in Group C. Because complex NBs (Types III to V) and various intracytoplasmic and intranuclear inclusions present in Group A are often associated with viral invasion, their presence in kidneys of AIDS patients with proteinuria suggests a viral etiology for AAN.

Collapsing glomerulopathy is an aggressive morphologic variant of focal segmental glomerulosclerosis which typically presents with nephrotic syndrome and rapidly progressive renal failure. Most cases of collapsing glomerulopathy are associated with human immunodeficiency virus infection. We present a rare case of collapsing glomerulopathy associated with acute cytomegalovirus (CMV) infection in an immunocompetent host with improvement in renal function after the treatment of CMV with ganciclovir. CMV may be an under-recognized cause of collapsing glomerulopathy which may respond to antiviral treatment.

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-κB and characterized by increased tumor necrosis factor-α and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.