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Revista Da Associacao Medica Brasileira... Jan 2020Chronic kidney disease is highly prevalent (10-13% of the population), irreversible, progressive, and associated with higher cardiovascular risk. Patients with this... (Review)
Review
Chronic kidney disease is highly prevalent (10-13% of the population), irreversible, progressive, and associated with higher cardiovascular risk. Patients with this pathology remain asymptomatic most of the time, presenting the complications typical of renal dysfunction only in more advanced stages. Its treatment can be conservative (patients without indication for dialysis, usually those with glomerular filtration rate above 15 ml/minute) or replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplantation). The objectives of the conservative treatment for chronic kidney disease are to slow down the progression of kidney dysfunction, treat complications (anemia, bone diseases, cardiovascular diseases), vaccination for hepatitis B, and preparation for kidney replacement therapy.
Topics: Humans; Kidney Failure, Chronic; Prevalence; Renal Dialysis; Renal Insufficiency; Renal Insufficiency, Chronic; Risk Factors
PubMed: 31939529
DOI: 10.1590/1806-9282.66.S1.3 -
The Lancet. Oncology Nov 2014This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing... (Review)
Review
This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfil the criteria for the presence of myeloma-defining CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specific metrics that new biomarkers should meet for inclusion in the disease definition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any differences in outcome that might occur as a result of the new disease definition.
Topics: Biomarkers, Tumor; Bone Marrow Cells; Humans; Multiple Myeloma; Prognosis; Renal Insufficiency
PubMed: 25439696
DOI: 10.1016/S1470-2045(14)70442-5 -
Journal of the American Society of... May 2019Senescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in the kidney and other organs with ageing and injury.... (Review)
Review
Senescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in the kidney and other organs with ageing and injury. Senescence has diverse physiologic roles and experimental studies support its importance in nephrogenesis, successful tissue repair, and in opposing malignant transformation. However, recent murine studies have shown that depletion of chronically senescent cells extends healthy lifespan and delays age-associated disease-implicating senescence and the senescence-associated secretory phenotype as drivers of organ dysfunction. Great interest is therefore focused on the manipulation of senescence as a novel therapeutic target in kidney disease. In this review, we examine current knowledge and areas of ongoing uncertainty regarding senescence in the human kidney and experimental models. We summarize evidence supporting the role of senescence in normal kidney development and homeostasis but also senescence-induced maladaptive repair, renal fibrosis, and transplant failure. Recent studies using senescent cell manipulation and depletion as novel therapies to treat renal disease are discussed, and we explore unanswered questions for future research.
Topics: Aging; Animals; Cellular Senescence; Humans; Kidney; Mice; Models, Animal; Prognosis; Renal Insufficiency, Chronic
PubMed: 31000567
DOI: 10.1681/ASN.2018121251 -
International Journal of Molecular... Aug 2021Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from... (Review)
Review
Molecular Biological and Clinical Understanding of the Pathophysiology and Treatments of Hyperuricemia and Its Association with Metabolic Syndrome, Cardiovascular Diseases and Chronic Kidney Disease.
Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Disease Management; Disease Susceptibility; Humans; Hyperuricemia; Metabolic Syndrome; Renal Insufficiency, Chronic; Severity of Illness Index
PubMed: 34502127
DOI: 10.3390/ijms22179221 -
Nephrology, Dialysis, Transplantation :... Dec 2019There have been significant recent advances in our understanding of the mechanisms that maintain potassium homoeostasis and the clinical consequences of hyperkalemia. In... (Review)
Review
There have been significant recent advances in our understanding of the mechanisms that maintain potassium homoeostasis and the clinical consequences of hyperkalemia. In this article we discuss these advances within a concise review of the pathophysiology, risk factors and consequences of hyperkalemia. We highlight aspects that are of particular relevance for clinical practice. Hyperkalemia occurs when renal potassium excretion is limited by reductions in glomerular filtration rate, tubular flow, distal sodium delivery or the expression of aldosterone-sensitive ion transporters in the distal nephron. Accordingly, the major risk factors for hyperkalemia are renal failure, diabetes mellitus, adrenal disease and the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or potassium-sparing diuretics. Hyperkalemia is associated with an increased risk of death, and this is only in part explicable by hyperkalemia-induced cardiac arrhythmia. In addition to its well-established effects on cardiac excitability, hyperkalemia could also contribute to peripheral neuropathy and cause renal tubular acidosis. Hyperkalemia-or the fear of hyperkalemia-contributes to the underprescription of potentially beneficial medications, particularly in heart failure. The newer potassium binders could play a role in attempts to minimize reduced prescribing of renin-angiotensin inhibitors and mineraolocorticoid antagonists in this context.
Topics: Global Health; Glomerular Filtration Rate; Heart Failure; Homeostasis; Humans; Hyperkalemia; Incidence; Potassium; Renal Insufficiency; Risk Factors
PubMed: 31800080
DOI: 10.1093/ndt/gfz206 -
International Journal of Molecular... Sep 2021Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association... (Review)
Review
Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association with multiple complications, including altered mineral metabolism, anemia, metabolic acidosis, and increased cardiovascular events. The mainstay of treatments for CKD lies in the prevention of the development and progression of CKD as well as its complications. Due to the heterogeneous origins and the uncertainty in the pathogenesis of CKD, efficacious therapies for CKD remain challenging. In this review, we focus on the following four themes: first, a summary of the known factors that contribute to CKD development and progression, with an emphasis on avoiding acute kidney injury (AKI); second, an etiology-based treatment strategy for retarding CKD, including the approaches for the common and under-recognized ones; and third, the recommended approaches for ameliorating CKD complications, and the final section discusses the novel agents for counteracting CKD progression.
Topics: Acidosis; Acute Kidney Injury; Anemia; Culture Media, Conditioned; Diabetes Complications; Diabetes Mellitus; Disease Progression; Epithelial-Mesenchymal Transition; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Kidney Failure, Chronic; Mesenchymal Stem Cells; Nephrolithiasis; Renal Insufficiency, Chronic
PubMed: 34576247
DOI: 10.3390/ijms221810084 -
Zoological Research Mar 2018Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in... (Review)
Review
Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in recent years. Due to the multiple causes of renal failure, many animal models have been developed to advance our understanding of human nephropathy. Among these experimental models, rodents have been extensively used to enable mechanistic understanding of kidney disease induction and progression, as well as to identify potential targets for therapy. In this review, we discuss AKI models induced by surgical operation and drugs or toxins, as well as a variety of CKD models (mainly genetically modified mouse models). Results from recent and ongoing clinical trials and conceptual advances derived from animal models are also explored.
Topics: Acute Kidney Injury; Animals; Disease Models, Animal; Humans; Kidney Diseases; Mice; Rats; Renal Insufficiency, Chronic
PubMed: 29515089
DOI: 10.24272/j.issn.2095-8137.2017.055 -
Journal of the American Society of... Jul 2018Sirtuins belong to an evolutionarily conserved family of NAD-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair,... (Review)
Review
Sirtuins belong to an evolutionarily conserved family of NAD-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1-7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging. In the kidney, the most widely studied sirtuin is SIRT1, which exerts cytoprotective effects by inhibiting cell apoptosis, inflammation, and fibrosis together with SIRT3, a crucial metabolic sensor that regulates ATP generation and mitochondrial adaptive response to stress. Here, we provide an overview of the biologic effects of sirtuins and the molecular targets thereof regulating renal physiology. This review also details progress made in understanding the effect of sirtuins in the pathophysiology of chronic and acute kidney diseases, highlighting the key role of SIRT1, SIRT3, and now SIRT6 as potential therapeutic targets. In this context, the current pharmacologic approaches to enhancing the activity of SIRT1 and SIRT3 will be discussed.
Topics: Acute Kidney Injury; Aging; Animals; Diabetic Nephropathies; Fibrosis; Humans; Kidney; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sirtuin 1; Sirtuins
PubMed: 29712732
DOI: 10.1681/ASN.2017111218 -
Nephron 2023There is a pandemic of obesity worldwide and in Europe up to 30% of the adult population is already obese. Obesity is strongly related to the risk of CKD, progression of... (Review)
Review
There is a pandemic of obesity worldwide and in Europe up to 30% of the adult population is already obese. Obesity is strongly related to the risk of CKD, progression of CKD, and end-stage renal disease (ESRD), also after adjustment for age, sex, race, smoking status, comorbidities, and laboratory tests. In the general population, obesity increases the risk of death. In nondialysis-dependent CKD patients, the association between body mass index and weight with mortality is controversial. In ESRD patients, obesity is paradoxically associated with better survival. There are only a few studies investigating changes in weight in these patients and in most weight loss was associated with higher mortality. However, it is not clear if weight change was intentional or unintentional and this is an important limitation of these studies. Management of obesity includes life-style interventions, bariatric surgery, and pharmacotherapy. In the last 2 years, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist and GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist were shown to be effective in managing weight loss in non-CKD patients, but we are awaiting results of more definitive studies in CKD patients.
Topics: Adult; Humans; Renal Insufficiency, Chronic; Obesity; Kidney Failure, Chronic; Weight Loss; Glucagon-Like Peptide 1
PubMed: 37271131
DOI: 10.1159/000531379 -
Nature Reviews. Nephrology Jul 2015Improved understanding of the oxygen-dependent regulation of erythropoiesis has provided new insights into the pathogenesis of anaemia associated with renal failure and... (Review)
Review
Improved understanding of the oxygen-dependent regulation of erythropoiesis has provided new insights into the pathogenesis of anaemia associated with renal failure and has led to the development of novel therapeutic agents for its treatment. Hypoxia-inducible factor (HIF)-2 is a key regulator of erythropoiesis and iron metabolism. HIF-2 is activated by hypoxic conditions and controls the production of erythropoietin by renal peritubular interstitial fibroblast-like cells and hepatocytes. In anaemia associated with renal disease, erythropoiesis is suppressed due to inadequate erythropoietin production in the kidney, inflammation and iron deficiency; however, pharmacologic agents that activate the HIF axis could provide a physiologic approach to the treatment of renal anaemia by mimicking hypoxia responses that coordinate erythropoiesis with iron metabolism. This Review discusses the functional inter-relationships between erythropoietin, iron and inflammatory mediators under physiologic conditions and in relation to the pathogenesis of renal anaemia, as well as recent insights into the molecular and cellular basis of erythropoietin production in the kidney. It furthermore provides a detailed overview of current clinical experience with pharmacologic activators of HIF signalling as a novel comprehensive and physiologic approach to the treatment of anaemia.
Topics: Anemia; Basic Helix-Loop-Helix Transcription Factors; Cell Hypoxia; Erythropoiesis; Humans; Hypoxia-Inducible Factor 1; Renal Insufficiency, Chronic; Signal Transduction
PubMed: 26055355
DOI: 10.1038/nrneph.2015.82