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Is the kidney a target of SARS-CoV-2?
Martinez-Rojas, MA, Vega-Vega, O, Bobadilla, NA
American journal of physiology. Renal physiology. 2020;(6):F1454-F1462
Abstract
The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multiorgan failure. Like other coronaviruses, SARS-CoV-2 recognizes human angiotensin-converting enzyme 2 as a cellular receptor that allows it to infect different host cells and likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, a considerable incidence of many renal abnormalities associated to COVID-19 has been reported, including proteinuria, hematuria, and acute kidney injury. Moreover, it has been recently demonstrated that SARS-CoV-2 can infect podocytes and tubular epithelial cells, which could contribute to the development of the aforementioned renal abnormalities. In this review, we discuss the biological aspects of SARS-CoV-2 infection, how understanding current knowledge about SARS-CoV-2 infection may partly explain the involvement of the kidneys in the pathophysiology of COVID-19, and what questions have arisen and remain to be explored.
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Kidney disease associated with androgenic-anabolic steroids and vitamin supplements abuse: Be aware!
Parente Filho, SLA, Gomes, PEAC, Forte, GA, Lima, LLL, Silva Júnior, GBD, Meneses, GC, Martins, AMC, Daher, EF
Nefrologia. 2020;(1):26-31
Abstract
The excessive chase for beauty standards and the rise of muscle dysmorphia have ultimately led to an increase in androgenic-anabolic steroids (AAS) and intramuscular injections of vitamins A, D and E (ADE) abuse, which is associated with several adverse effects and has become a public health issue. This review of literature discusses kidney injury associated with the use of AAS and ADE, highlighting the mechanisms of acute and chronic renal lesion, such as direct renal toxicity, glomerular hyperfiltration and hypercalcemia. Future perspectives regarding evaluation and early diagnosis of kidney injury in these patients are also discussed.
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An expanding spectrum of complications in isolated methylmalonic aciduria.
Forny, P, Grunewald, S
Journal of mother and child. 2020;(2):9-13
Abstract
Isolated methylmalonic acidurias represent a heterogeneous genetic group of inborn errors of propionate metabolism with the common biochemical hallmark of elevated methylmalonic acid present in tissues and body fluids. It was first described in the 1960s and over the years better understanding of the disease and its presentation, earlier diagnosis, and most importantly advances in treatment have resulted in extended survival of patients. With that an expanding spectrum of complications is emerging which requires attention and regular monitoring to facilitate early intervention and reduce disease burden.
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Unravelling the complex genetics of common kidney diseases: from variants to mechanisms.
Sullivan, KM, Susztak, K
Nature reviews. Nephrology. 2020;(11):628-640
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Abstract
Genome-wide association studies (GWAS) have identified hundreds of loci associated with kidney-related traits such as glomerular filtration rate, albuminuria, hypertension, electrolyte and metabolite levels. However, these impressive, large-scale mapping approaches have not always translated into an improved understanding of disease or development of novel therapeutics. GWAS have several important limitations. Nearly all disease-associated risk loci are located in the non-coding region of the genome and therefore, their target genes, affected cell types and regulatory mechanisms remain unknown. Genome-scale approaches can be used to identify associations between DNA sequence variants and changes in gene expression (quantified through bulk and single-cell methods), gene regulation and other molecular quantitative trait studies, such as chromatin accessibility, DNA methylation, protein expression and metabolite levels. Data obtained through these approaches, used in combination with robust computational methods, can deliver robust mechanistic inferences for translational exploitation. Understanding the genetic basis of common kidney diseases means having a comprehensive picture of the genes that have a causal role in disease development and progression, of the cells, tissues and organs in which these genes act to affect the disease, of the cellular pathways and mechanisms that drive disease, and of potential targets for disease prevention, detection and therapy.
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[Immune check point inhibitor-associated renal toxicity].
Izzedine, H, Gueutin, V
Nephrologie & therapeutique. 2020;(1):19-26
Abstract
Immune checkpoint inhibition had a major clinical success in clinical oncology and impacted the treatment paradigm in many cancers. Immune related adverse events are well-described toxicities that are closely associated with CPI therapies and can involve any organ in the body. Renal toxicity is multifocal. In addition to the predominant tubulointerstitial involvement, immunotherapy can lead to a variety of glomerular damage and electrolyte disorders. Suggested mechanisms include direct renal interstitium lymphocyte infiltration, renal immune complex deposition, microangiopathic endothelial disease, or cytokine release leading to podocytopathy. Immunotherapy in the renal transplant patient raises the question of the rejection occurrence. Current recommendations for diagnosis and management of renal effects are not optimal because of the limited data available and understanding of their pathophysiology.
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A diagnostician's field guide to crystalline nephropathies.
Nicholas Cossey, L, Dvanajscak, Z, Larsen, CP
Seminars in diagnostic pathology. 2020;(3):135-142
Abstract
The kidney's role in filtration of blood and production of urine occurs via a combination of size and charge filtration at the glomerular basement membrane and resorption and excretion of molecules through a complex tubular system embedded within an ion gradient. This delicate system provides the kidney with a unique propensity for substrate saturation and crystal nucleation within the nephron. While crystalline nephropathies may seem exotic to the uninitiated, they are comprised of easily recognizable morphologies and generally lack complicated classification schemas. Additionally, unlike many intrinsic kidney diseases, crystalline nephropathies are often associated with systemic conditions that, upon further investigation, may elucidate critically important information. This review focuses on practical, diagnostically relevant and high yield information that can be utilized by diagnosticians. Our hope is to equip the reader who reviews renal tissue with a practical toolkit that they feel empowered to use when faced with crystal formation in a kidney biopsy, pre-implantation biopsy, or nephrectomy specimen. Short Abstract The kidney's role in filtration of blood and production of urine provides a unique propensity for substrate saturation and crystal nucleation within the nephron. While crystalline nephropathies may seem exotic to the uninitiated, they are comprised of easily recognizable morphologies and generally lack complicated classification. Additionally, crystalline nephropathies are often associated with systemic conditions that, upon further investigation, may elucidate critically important information.
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Drug Development in Kidney Disease: Proceedings From a Multistakeholder Conference.
Edmonston, DL, Roe, MT, Block, G, Conway, PT, Dember, LM, DiBattiste, PM, Greene, T, Hariri, A, Inker, LA, Isakova, T, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2020;(6):842-850
Abstract
Occasional bursts of discovery and innovation have appeared during the otherwise stagnant past several decades of drug development in nephrology. Among other recent drug discoveries, the unexpected kidney benefits observed with sodium/glucose cotransporter 2 inhibitors may herald a renaissance of drug development in kidney disease. This recent progress highlights the need to further promote and stimulate research and development of promising therapies that may ameliorate the morbidity and mortality associated with kidney disease. To help identify and address barriers to drug development in nephrology, the Duke Clinical Research Institute convened a conference in April 2019 that included stakeholders from academia, industry, government agencies, and patient advocacy. From these discussions, several opportunities were identified to improve every stage of drug development for kidney disease from early discovery to implementation into practice. Key topics reviewed in this article are the utility of interconnected data and site research networks, surrogate end points, pragmatic and adaptive trial designs, the promising uses of real-world data, and methods to improve the generalizability of trial results and uptake of approved drugs for kidney-related diseases.
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Vitamin K effects in human health: new insights beyond bone and cardiovascular health.
Fusaro, M, Gallieni, M, Porta, C, Nickolas, TL, Khairallah, P
Journal of nephrology. 2020;(2):239-249
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Abstract
Vitamin K is a cofactor for the function of the enzyme γ-glutamyl carboxylase, necessary for the activation of multiple vitamin K dependent-proteins. Vitamin K dependent-proteins (VKDPs) have important roles in bone health, vascular health, metabolism, reproduction as well as in cancer progression. Vitamin K deficiency is common in different conditions, including kidney disease, and it may influence the activity of VKDPs. This review discusses vitamin K status in human health and the physiologic and pathologic roles of VKDPs, beyond the established effects in skeletal and cardiovascular health.
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Dose discordance of direct acting oral anticoagulants using different equations for estimating GFR: a literature review.
Nabiee, M, Dashti-Khavidaki, S, Khajeh, B
Expert review of clinical pharmacology. 2020;(8):857-863
Abstract
INTRODUCTION Direct oral anticoagulants (DOACs) are widely prescribed nowadays. Available DOACs are renally eliminated to some extent and need dose adjustment in patients with kidney dysfunction. Cockcroft-Gault (CG) formula has been used to estimate creatinine clearance in DOACs trials. Nowadays, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are preferred equations for estimating glomerular filtration rate (GFR). We reviewed studies that simulated DOACs dosing in patients with atrial fibrillation by MDRD, CKD-EPI, and CG. AREAS COVERED DOACs dose discordance varies from 28.8% underdosing to 59.2% overdosing when MDRD or CKD-EPI equations are substituted for CG. MDRD and CKD-EPI overestimate the GFR in lower thresholds of kidney function especially in elderly and females and result in overestimation of DOACs dosing or misclassifying the patients to be eligible for receiving DOACs when they are contraindicated. Compared with CG, MDRD and CKD-EPI underestimate the level of kidney function in higher GFR extremes and in these patients suggest DOACs when they are not recommended or suggest lower doses. EXPERT OPINION Until running large clinical studies on efficacy/safety of DOACs dosing using MDRD or CKD-EPI equations, use of CG method for DOACs dosing is recommended in real practice.
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Nocturia: The Complex Role of the Heart, Kidneys, and Bladder.
Lombardo, R, Tubaro, A, Burkhard, F
European urology focus. 2020;(3):534-536
Abstract
We review the role of the heart, kidneys, and bladder in the pathophysiology of nocturia and nocturnal polyuria. Lower urinary tract symptoms such as nocturia have often been associated with lower urinary tract dysfunction. It is known that the bladder contributes to nocturia in the case of low functional capacity, urgency, and detrusor overactivity. Heart diseases, especially arterial hypertension and congestive heart failure, are closely related to nocturnal polyuria. The main mechanisms include renal hyperfiltration and elevated atrial natriuretic peptide. A number of drugs frequently used in cardiovascular disorders are implicated in nocturia; diuretics, calcium channel blockers, and β-blockers induce nocturnal polyuria and thus nocturia, whereas alpha-blockers improve nocturia. Among the different forms of hypertension, nondipping arterial hypertension has been associated with a higher risk of nocturnal polyuria. Besides the role of the kidneys in nocturia linked to arterial hypertension, chronic kidney disease is an independent predictor of nocturia through an osmotic diuresis mechanism. Some evidence suggests a close relationship between the heart (nondipping arterial hypertension), kidneys (chronic kidney disease), and nocturia/nocturnal polyuria. These complex interactions between the heart, kidneys, and bladder warrant a multidisciplinary approach in patients with nocturia. PATIENT SUMMARY We review the different mechanisms that lead to nocturia and nocturnal polyuria. The complex interactions between the heart, the kidneys, and the bladder warrant a multidisciplinary approach in patients with nocturia. Careful investigation of the cause of nocturia can improve its management.