0
selected
-
1.
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.
-
2.
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.
-
3.
[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.
-
4.
Renal Toxicities of Novel Agents Used for Treatment of Multiple Myeloma.
Wanchoo, R, Abudayyeh, A, Doshi, M, Edeani, A, Glezerman, IG, Monga, D, Rosner, M, Jhaveri, KD
Clinical journal of the American Society of Nephrology : CJASN. 2017;(1):176-189
-
-
Free full text
-
Abstract
Survival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma.
-
5.
Kidney disease and psoriasis: novel evidences beyond old concepts.
Visconti, L, Leonardi, G, Buemi, M, Santoro, D, Cernaro, V, Ricciardi, CA, Lacquaniti, A, Coppolino, G
Clinical rheumatology. 2016;(2):297-302
Abstract
Psoriasis is an immune-mediated inflammatory disease for a long time considered as a type of pathology characterized by an exclusive skin involvement. Recently it has been shown that patients affected by this disease have a higher risk of developing comorbidities such as cardiovascular diseases, arterial hypertension, diabetes mellitus, and metabolic syndrome. Even the kidneys can be affected by psoriasis through three different mechanisms: immune-mediated renal damage, drug-related renal damage and chronic renal damage. Renal function should be monitored periodically to minimize the risk of renal adverse events.
-
6.
Effects of gluten-free, dairy-free diet on childhood nephrotic syndrome and gut microbiota.
Uy, N, Graf, L, Lemley, KV, Kaskel, F
Pediatric research. 2015;(1-2):252-5
-
-
Free full text
-
Abstract
Emerging evidence suggests an association between food sensitivity and gut microbiota in children with nephrotic syndrome. Diminished proteinuria resulted from eliminating cow's milk and the use of an oligoantigenic diet which excluded gluten, especially in patients with immune-related conditions, i.e., celiac disease and nephrotic syndrome. The mechanisms underlying the association of diet, gut microbiota, and dysregulation of the immune system are unknown. Gut microbiota is influenced by a number of factors including diet composition and other environmental epigenetic exposures. The imbalance in gut microbiota may be ameliorated by gluten-free and dairy-free diets. Gluten-free diet increased the number of unhealthy bacteria while reducing bacterial-induced cytokine production of IL-10. Thus, gluten-free diet may influence the composition and immune function of gut microbiota and should be considered a possible environmental factor associated with immune-related disease, including nephrotic syndrome. Furthermore, the imbalance of gut microbiota may be related to the development of cow's milk protein allergy. Investigations are needed to fill the gaps in our knowledge concerning the associations between the gut microbiome, environmental exposures, epigenetics, racial influences, and the propensity for immune dysregulation with its inherent risk to the developing individual.
-
7.
Mechanisms and biological functions of autophagy in diseased and ageing kidneys.
Fougeray, S, Pallet, N
Nature reviews. Nephrology. 2015;(1):34-45
Abstract
Autophagy degrades pathogens, altered organelles and protein aggregates, and is characterized by the sequestration of cytoplasmic cargos within double-membrane-limited vesicles called autophagosomes. The process is regulated by inputs from the cellular microenvironment, and is activated in response to nutrient scarcity and immune triggers, which signal through a complex molecular network. Activation of autophagy leads to the formation of an isolation membrane, recognition of cytoplasmic cargos, expansion of the autophagosomal membrane, fusion with lysosomes and degradation of the autophagosome and its contents. Autophagy maintains cellular homeostasis during stressful conditions, dampens inflammation and shapes adaptive immunity. A growing body of evidence has implicated autophagy in kidney health, ageing and disease; it modulates tissue responses during acute kidney injuries, regulates podocyte homeostasis and protects against age-related renal disorders. The renoprotective functions of autophagy in epithelial renal cells and podocytes are mostly mediated by the clearance of altered mitochondria, which can activate inflammasomes and apoptosis, and the removal of protein aggregates, which might trigger inflammation and cell death. In translational terms, autophagy is undoubtedly an attractive target for developing new renoprotective treatments and identifying markers of kidney injury.
-
8.
[Kidney and thyroid dysfunction].
Ponsoye, M, Paule, R, Gueutin, V, Deray, G, Izzedine, H
Nephrologie & therapeutique. 2013;(1):13-20
Abstract
Thyroid hormones influence renal development, kidney structure, renal hemodynamics, glomerular filtration rate, the function of many transport systems along the nephron, and sodium and water homeostasis. Effects of hypothyroidism and hyperthyroidism on kidney function are the result of direct renal effects, as well as systemic hemodynamic, metabolic, and cardiovascular effects. Most of the renal manifestations of thyroid disorders, which are clinically most significant with hypothyroidism, are reversible with treatment. Patients with hypothyroidism can have clinically important reductions in GFR, so screening for hypothyroidism should be considered in patients with unexplained elevations in serum creatinine. Patients with thyroid disorders are also at risk for immune-mediated glomerular diseases. Finally, patients with nephrotic syndrome, as well as acute and chronic kidney injury, have alterations in thyroid gland physiology that can impact thyroid function and the testing of thyroid function status. Dialysis patients have frequently hypothyroidism whose biological diagnosis must be careful.
-
9.
Use of vitamin D in chronic kidney disease patients.
Gal-Moscovici, A, Sprague, SM
Kidney international. 2010;(2):146-51
Abstract
Chronic kidney disease (CKD) has been recognized as a significant public health problem, with 20 million Americans, or 11% of the adult population, currently living with CKD. Life expectancy in patients with CKD is limited by the development of disturbances of mineral metabolism, which occurs in virtually all patients during the progression of their disease, and is associated with bone loss and fractures, cardiovascular disease, immune suppression, and increased mortality. As kidney disease develops, there is decreased functional renal mass and a reduction in renal 1alpha-hydroxylase activity and thus in renal production of calcitriol at very early CKD stages. Recently, a potentially important role of vitamin D receptor activation (VDRa) in the survival of patients undergoing dialysis has been suggested. Beyond the effect on parathyroid hormone suppression, the pleiotropic effect of vitamin D has been associated with improvement of cardiovascular risk factors, including increased renin activity, hypertension, inflammation, insulin resistance, diabetes, and albuminuria. However, the current K/DOQI and KDIGO recommendations limit the administration of VDRa agents for treatment of hyperparathyroidism only. The role of vitamin D administration in the different CKD stages will be discussed in this review.