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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 -
Advances in Therapy Jan 2022Chronic kidney disease (CKD) is a complex disease which affects approximately 13% of the world's population. Over time, CKD can cause renal dysfunction and progression... (Review)
Review
Chronic kidney disease (CKD) is a complex disease which affects approximately 13% of the world's population. Over time, CKD can cause renal dysfunction and progression to end-stage kidney disease and cardiovascular disease. Complications associated with CKD may contribute to the acceleration of disease progression and the risk of cardiovascular-related morbidities. Early CKD is asymptomatic, and symptoms only present at later stages when complications of the disease arise, such as a decline in kidney function and the presence of other comorbidities associated with the disease. In advanced stages of the disease, when kidney function is significantly impaired, patients can only be treated with dialysis or a transplant. With limited treatment options available, an increasing prevalence of both the elderly population and comorbidities associated with the disease, the prevalence of CKD is set to rise. This review discusses the current challenges and the unmet patient need in CKD.
Topics: Aged; Cardiovascular Diseases; Disease Progression; Humans; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 34739697
DOI: 10.1007/s12325-021-01927-z -
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 -
Nature Reviews. Nephrology May 2021Mitochondria are essential for the activity, function and viability of eukaryotic cells and mitochondrial dysfunction is involved in the pathogenesis of acute kidney... (Review)
Review
Mitochondria are essential for the activity, function and viability of eukaryotic cells and mitochondrial dysfunction is involved in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease, as well as in abnormal kidney repair after AKI. Multiple quality control mechanisms, including antioxidant defence, protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy and mitochondrial biogenesis, have evolved to preserve mitochondrial homeostasis under physiological and pathological conditions. Loss of these mechanisms may induce mitochondrial damage and dysfunction, leading to cell death, tissue injury and, potentially, organ failure. Accumulating evidence suggests a role of disturbances in mitochondrial quality control in the pathogenesis of AKI, incomplete or maladaptive kidney repair and chronic kidney disease. Moreover, specific interventions that target mitochondrial quality control mechanisms to preserve and restore mitochondrial function have emerged as promising therapeutic strategies to prevent and treat kidney injury and accelerate kidney repair. However, clinical translation of these findings is challenging owing to potential adverse effects, unclear mechanisms of action and a lack of knowledge of the specific roles and regulation of mitochondrial quality control mechanisms in kidney resident and circulating cell types during injury and repair of the kidney.
Topics: Acute Kidney Injury; Animals; Humans; Mitochondria; Renal Insufficiency, Chronic
PubMed: 33235391
DOI: 10.1038/s41581-020-00369-0 -
Vascular Health and Risk Management 2021The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI)... (Review)
Review
The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis.
The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction.
Topics: Acute Disease; Biomarkers; Humans; Myocardial Infarction; Physical Exertion; Pulmonary Embolism; Pulmonary Heart Disease; Renal Insufficiency; Sepsis; Troponin; Troponin I; Troponin T
PubMed: 34584417
DOI: 10.2147/VHRM.S327661 -
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 -
Clinical Journal of the American... Feb 2020Hematopoietic stem cell transplantation is a life-saving therapy for many patients with cancer, as well as patients with some nonmalignant hematologic disorders, such as... (Review)
Review
Hematopoietic stem cell transplantation is a life-saving therapy for many patients with cancer, as well as patients with some nonmalignant hematologic disorders, such as aplastic anemia, sickle cell disease, and certain congenital immune deficiencies. Kidney injury directly associated with stem cell transplantation includes a wide range of structural and functional abnormalities, which may be vascular (hypertension, thrombotic microangiopathy), glomerular (albuminuria, nephrotic glomerulopathies), and/or tubulointerstitial. AKI occurs commonly after stem cell transplant, affecting 10%-73% of patients. The cause is often multifactorial and can include sepsis, nephrotoxic medications, marrow infusion syndrome, hepatic sinusoidal obstruction syndrome, thrombotic microangiopathy, infections, and graft versus host disease. The risk of post-transplant kidney injury varies depending on patient characteristics, type of transplant (allogeneic versus autologous), and choice of chemotherapeutic conditioning regimen (myeloablative versus nonmyeloablative). Importantly, AKI is associated with substantial morbidity, including the need for KRT in approximately 5% of patients and the development of CKD in up to 60% of transplant recipients. AKI has been associated universally with higher all-cause and nonrelapse mortality regardless of transplant type, and studies have consistently shown extremely high (>80%) mortality rates in those patients requiring acute dialysis. Accordingly, prevention, early recognition, and prompt treatment of kidney injury are essential to improving kidney and patient outcomes after hematopoietic stem cell transplantation, and for realizing the full potential of this therapy.
Topics: Acute Kidney Injury; Early Diagnosis; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 31836598
DOI: 10.2215/CJN.08580719 -
Kidney & Blood Pressure Research 2021Chronic kidney disease-associated pruritus (CKD-aP), also known as uraemic pruritus, is a disabling symptom for patients and a challenging condition for clinicians.... (Review)
Review
BACKGROUND
Chronic kidney disease-associated pruritus (CKD-aP), also known as uraemic pruritus, is a disabling symptom for patients and a challenging condition for clinicians. Despite being common amongst end-stage kidney disease (ESKD) patients, it remains underestimated and underdiagnosed. The exact pathogenesis remains largely elusive, which hampers the synthesis of a definite treatment approach.
SUMMARY
Chronic pruritus (lasting 6 weeks or more in duration) is a common and potentially disabling symptom in patients with advanced CKD. A unified hypothesis of pathogenesis has not yet been concluded. Studies have shown changes in the immunochemical milieu of the skin in patients with CKD-aP with several inciting stimuli identified. However, other unrecognized factors are likely to be involved. This article will review the current observations and understanding of the postulated pathogenesis of CKD-aP, as well as the evidence for current management strategies. Key Messages: CKD-aP is a common and troubling symptom amongst ESKD patients that is associated with decreased quality of life and poor prognosis. Its exact pathogenesis, at the time of writing, is not well-understood. A stepwise approach is recommended for management. Systematic reviews show the largest body of evidence was found for the effectiveness of gabapentin. Comparison is needed between newly emerging pharmacological agents such as kappa-opioid receptor agonists and more established agents, such as the gabapentinoids. Finally, renal transplantation should be considered in severe and refractory cases who are suitable transplant candidates as it has shown an excellent outcome in most cases.
Topics: Disease Management; Disease Progression; Humans; Kidney Failure, Chronic; Pruritus; Quality of Life; Renal Insufficiency, Chronic
PubMed: 34515143
DOI: 10.1159/000518391