Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. The initial injuries ...vary widely. Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS. Varying phenotypes of the sclerosis are also manifest, with varying prognosis. The so-called tip lesion has the best prognosis, whereas the collapsing type of FSGS has the worst prognosis. New insights into glomerular cell injury response and repair may pave the way for possible therapeutic strategies.
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.
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AI applications in renal pathology Huo, Yuankai; Deng, Ruining; Liu, Quan ...
Kidney international,
06/2021, Letnik:
99, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The explosive growth of artificial intelligence (AI) technologies, especially deep learning methods, has been translated at revolutionary speed to efforts in AI-assisted healthcare. New applications ...of AI to renal pathology have recently become available, driven by the successful AI deployments in digital pathology. However, synergetic developments of renal pathology and AI require close interdisciplinary collaborations between computer scientists and renal pathologists. Computer scientists should understand that not every AI innovation is translatable to renal pathology, while renal pathologists should capture high-level principles of the relevant AI technologies. Herein, we provide an integrated review on current and possible future applications in AI-assisted renal pathology, by including perspectives from computer scientists and renal pathologists. First, the standard stages, from data collection to analysis, in full-stack AI-assisted renal pathology studies are reviewed. Second, representative renal pathology-optimized AI techniques are introduced. Last, we review current clinical AI applications, as well as promising future applications with the recent advances in AI.
Pathologists use visual classification of glomerular lesions to assess samples from patients with diabetic nephropathy (DN). The results may vary among pathologists. Digital algorithms may reduce ...this variability and provide more consistent image structure interpretation.
We developed a digital pipeline to classify renal biopsies from patients with DN. We combined traditional image analysis with modern machine learning to efficiently capture important structures, minimize manual effort and supervision, and enforce biologic prior information onto our model. To computationally quantify glomerular structure despite its complexity, we simplified it to three components consisting of nuclei, capillary lumina and Bowman spaces; and Periodic Acid-Schiff positive structures. We detected glomerular boundaries and nuclei from whole slide images using convolutional neural networks, and the remaining glomerular structures using an unsupervised technique developed expressly for this purpose. We defined a set of digital features which quantify the structural progression of DN, and a recurrent network architecture which processes these features into a classification.
Our digital classification agreed with a senior pathologist whose classifications were used as ground truth with moderate Cohen's kappa κ = 0.55 and 95% confidence interval 0.50, 0.60. Two other renal pathologists agreed with the digital classification with κ
= 0.68, 95% interval 0.50, 0.86 and κ
= 0.48, 95% interval 0.32, 0.64. Our results suggest computational approaches are comparable to human visual classification methods, and can offer improved precision in clinical decision workflows. We detected glomerular boundaries from whole slide images with 0.93±0.04 balanced accuracy, glomerular nuclei with 0.94 sensitivity and 0.93 specificity, and glomerular structural components with 0.95 sensitivity and 0.99 specificity.
Computationally derived, histologic image features hold significant diagnostic information that may augment clinical diagnostics.
We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an ...international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents. The term “endocapillary proliferation” is eliminated and the definition of endocapillary hypercellularity considered in some detail. We also eliminate the class IV-S and IV-G subdivisions of class IV lupus nephritis. The active and chronic designations for class III/IV lesions are replaced by a proposal for activity and chronicity indices that should be applied to all classes. In the activity index, we include fibrinoid necrosis as a specific descriptor. We also make recommendations on issues for which there are limited data at present and that can best be addressed in future studies (phase 2). We propose to proceed to these investigations, with clinicopathologic studies and tests of interobserver reproducibility to evaluate the applications of the proposed definitions and to classify lupus nephritis lesions.
Chronic kidney disease (CKD) occurs in all age groups, including children. Regardless of the underlying cause, CKD is characterized by progressive scarring that ultimately affects all structures of ...the kidney. The relentless progression of CKD is postulated to result from a self-perpetuating vicious cycle of fibrosis activated after initial injury. We will review possible mechanisms of progressive renal damage, including systemic and glomerular hypertension, various cytokines and growth factors, with special emphasis on the renin-angiotensin-aldosterone system (RAAS), podocyte loss, dyslipidemia and proteinuria. We will also discuss possible specific mechanisms of tubulointerstitial fibrosis that are not dependent on glomerulosclerosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number.
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