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1.
Renoprotection with sodium-glucose cotransporter-2 inhibitors in children: Knowns and unknowns.
Jiang, B, Cheng, Z, Liu, F, Li, Q, Fu, H, Mao, J
Nephrology (Carlton, Vic.). 2022;(2):126-132
Abstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent novel hypoglycemic drugs for the treatment of adult diabetes that have shown considerable potential for cardioprotection and renoprotection. This new drug can inhibit SGLT2 at the proximal tubule, increase glucosuria and natriuresis, and thus decreases the serum glucose level and blood pressure. Furthermore, the tubuloglomerular feedback activated by the natriuresis can decrease glomerular hyperfiltration, acknowledged as the main foundation of renoprotection. Several studies have confirmed the protective effects of SGLT2 inhibitors on the kidneys of adult diabetic patients and those with non-diabetic nephropathy; however, limited researches are seen in paediatric patients. In this review, we have summarized the mechanisms of action of SGLT2 inhibitors, the current experiences in adults, results of exploratory studies in children, and adverse events & obstacles of paediatric use. We further explore the potential and possible future research direction of SGLT2 inhibitors in paediatric diseases.
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2.
Kidney function monitoring in inflammatory bowel disease: The MONITORED consensus.
Guillo, L, Delanaye, P, Flamant, M, Figueres, L, Karam, S, Lemoine, S, Benezech, A, Pelletier, AL, Amiot, A, Caron, B, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(3):309-315
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Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD. METHODS A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement. RESULTS Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient. CONCLUSION The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients.
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The Continuum of Acid Stress.
Wesson, DE
Clinical journal of the American Society of Nephrology : CJASN. 2021;(8):1292-1299
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Abstract
Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This "acid stress" continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.
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Targeting immune cell metabolism in kidney diseases.
Basso, PJ, Andrade-Oliveira, V, Câmara, NOS
Nature reviews. Nephrology. 2021;(7):465-480
Abstract
Insights into the relationship between immunometabolism and inflammation have enabled the targeting of several immunity-mediated inflammatory processes that underlie infectious diseases and cancer or drive transplant rejection, but this field remains largely unexplored in kidney diseases. The kidneys comprise heterogeneous cell populations, contain distinct microenvironments such as areas of hypoxia and hypersalinity, and are responsible for a functional triad of filtration, reabsorption and secretion. These distinctive features create myriad potential metabolic therapeutic targets in the kidney. Immune cells have crucial roles in the maintenance of kidney homeostasis and in the response to kidney injury, and their function is intricately connected to their metabolic properties. Changes in nutrient availability and biomolecules, such as cytokines, growth factors and hormones, initiate cellular signalling events that involve energy-sensing molecules and other metabolism-related proteins to coordinate immune cell differentiation, activation and function. Disruption of homeostasis promptly triggers the metabolic reorganization of kidney immune and non-immune cells, which can promote inflammation and tissue damage. The metabolic differences between kidney and immune cells offer an opportunity to specifically target immunometabolism in the kidney.
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Potential Therapeutic Effects of Natural Plant Compounds in Kidney Disease.
Avila-Carrasco, L, García-Mayorga, EA, Díaz-Avila, DL, Garza-Veloz, I, Martinez-Fierro, ML, González-Mateo, GT
Molecules (Basel, Switzerland). 2021;(20)
Abstract
BACKGROUND The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. METHODS This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. RESULTS Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. CONCLUSIONS This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.
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Kidney injury and disease in patients with haematological malignancies.
Bridoux, F, Cockwell, P, Glezerman, I, Gutgarts, V, Hogan, JJ, Jhaveri, KD, Joly, F, Nasr, SH, Sawinski, D, Leung, N
Nature reviews. Nephrology. 2021;(6):386-401
Abstract
Acute kidney injury (AKI) is common in patients with cancer, especially in those with haematological malignancies. Kidney injury might be a direct consequence of the underlying haematological condition. For example, in the case of lymphoma infiltration or extramedullary haematopoiesis, it might be caused by a tumour product; in the case of cast nephropathy it might be due to the presence of monoclonal immunoglobulin; or it might result from tumour complications, such as hypercalcaemia. Kidney injury might also be caused by cancer treatment, as many chemotherapeutic agents are nephrotoxic. High-intensity treatments, such as high-dose chemotherapy followed by haematopoietic stem cell transplantation, not only increase the risk of infection but can also cause AKI through various mechanisms, including viral nephropathies, engraftment syndrome and sinusoidal obstruction syndrome. Some conditions, such as thrombotic microangiopathy, might also result directly from the haematological condition or the treatment. Novel immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cell therapy, can also be nephrotoxic. As new therapies for haematological malignancies with increased anti-tumour efficacy and reduced toxicity are developed, the number of patients receiving these treatments will increase. Clinicians must gain a good understanding of the different mechanisms of kidney injury associated with cancer to better care for these patients.
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The glycine betaine role in neurodegenerative, cardiovascular, hepatic, and renal diseases: Insights into disease and dysfunction networks.
Rosas-Rodríguez, JA, Valenzuela-Soto, EM
Life sciences. 2021;:119943
Abstract
Glycine betaine (N, N, N-trimethyl amine) is an osmolyte accumulated in cells that is key for cell volume and turgor regulation, is the principal methyl donor in the methionine cycle and is a DNA and proteins stabilizer. In humans, glycine betaine is synthesized from choline and can be obtained from some foods. Glycine betaine (GB) roles are illustrated in chemical, metabolic, agriculture, and clinical medical studies due to its chemical and physiological properties. Several studies have extensively described GB role and accumulation related to specific pathologies, focusing mainly on analyzing its positive and negative role in these pathologies. However, it is necessary to explain the relationship between glycine betaine and different pathologies concerning its role as an antioxidant, ability to methylate DNA, interact with transcription factors and cell receptors, and participate in the control of homocysteine concentration in liver, kidney and brain. This review summarizes the most important findings and integrates GB role in neurodegenerative, cardiovascular, hepatic, and renal diseases. Furthermore, we discuss GB impact on other dysfunctions as inflammation, oxidative stress, and glucose metabolism, to understand their cross-talks and provide reliable data to establish a base for further investigations.
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Inherited Tubulopathies of the Kidney: Insights from Genetics.
Downie, ML, Lopez Garcia, SC, Kleta, R, Bockenhauer, D
Clinical journal of the American Society of Nephrology : CJASN. 2021;(4):620-630
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Abstract
The kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we focus on genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of genetically defined patients have shaped our understanding of kidney physiology.
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The role of Elabela in kidney disease.
Zheng, Q, Tian, G, Xu, F, Ci, X, Luan, R, Wu, L, Lu, X
International urology and nephrology. 2021;(9):1851-1857
Abstract
Elabela, also known as Toddler or Apela, is a recently discovered hormonal peptide containing 32 amino acids. Elabela is a ligand of the apelin receptor (APJ). APJ is a G protein-coupled receptor widely expressed throughout body, and together with its cognate ligand, apelin, it plays an important role in various physiological processes including cardiovascular functions, angiogenesis and fluid homeostasis. Elabela also participates in embryonic development and pathophysiological processes in adulthood. Elabela is highly expressed in undifferentiated embryonic stem cells and regulates endoderm differentiation and cardiovascular system development. During differentiation, Elabela is highly expressed in pluripotent stem cells and in adult renal collecting ducts and loops, where it functions to maintain water and sodium homeostasis. Other studies have also shown that Elabela plays a crucial role in the pathogenesis of kidney diseases. This review addresses the role of Elabela in kidney diseases including renal ischemia/reperfusion injury, hypertensive nephropathy, diabetic nephropathy, and cardiorenal syndrome.
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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.