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1.
Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for cardiovascular and renal protection: A treatment approach far beyond their glucose-lowering effect.
Gómez-Huelgas, R, Sanz-Cánovas, J, Cobos-Palacios, L, López-Sampalo, A, Pérez-Belmonte, LM
European journal of internal medicine. 2022;:26-33
Abstract
Findings from cardiovascular outcome trials on certain newer glucose-lowering drugs have shown clear cardiovascular and renal benefits. In this review, we provide an updated overview of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors in terms of cardiovascular and renal protection. Both drugs have been described as diabetes/disease-modifying drugs. There is robust evidence on the benefits of GLP-1 receptor agonists in renal disease and atherosclerotic cardiovascular disease-especially in stroke-which are mainly explained by their antiproteinuric effect. However, this class of drugs has only shown neutral effects on heart failure and further studies are necessary in order to assess their role in this disease. SGLT-2 inhibitors have shown strong benefits in heart failure hospitalizations and renal outcomes, mainly through limiting glomerular filtration rate deterioration, regardless of the presence of diabetes. Nonetheless, their effect on the prevention of major adverse atherosclerotic cardiovascular events and cardiovascular mortality seems to be limited to patients with type 2 diabetes and established cardiovascular disease. Evidence on the cardiovascular and renal benefits of GLP-1 receptor agonists and SGLT-2 inhibitors have significantly modified management plans and treatment choices for patients with type 2 diabetes. There is now a focus on a multifactorial approach that goes beyond the glucose-lowering effect of these drugs, which are the preferred choice in routine clinical practice. According to the current evidence, a patient-focused approach that includes both individualized glycemic control and cardiorenal prevention using GLP-1 receptor agonists and SGLT-2 inhibitors with proven cardiovascular and renal benefits is believed to be the best strategy for achieving the treatment goals of patients with type 2 diabetes. Despite the strong cardiovascular and renal benefits of these drugs, further research is required in order to clarify questions that remain unanswered.
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2.
[Clinical and genetic analysis of a newborn with hypoparathyroidism, sensorineural hearing loss, and renal dysplasia syndrome].
Shao, Q, Wu, P, Lin, B, Chen, S, Liu, J, Chen, S
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2022;(2):222-226
Abstract
OBJECTIVE To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.
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3.
Reducing the Risk of Stroke in Patients with Impaired Renal Function: Nutritional Issues.
Spence, JD
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2021;(9):105376
Abstract
Patients with renal failure have extremely high cardiovascular risk; in dialysis patients the risk of stroke is increased approximately 10-fold over that in the general population. Reasons include not only a high prevalence of traditional risk factors such as diabetes, hypertension and dyslipidemia, but also the accumulation of toxic substances that are eliminated by the kidneys, so have very high levels in patients with renal failure. These include plasma total homocysteine, asymmetric dimethylarginine, thiocyanate, and toxic products of the intestinal microbiome (Gut-Derived Uremic Toxins; GDUT), which include trimethylamine N- oxide (TMAO), produced from phosphatidylcholine (largely from egg yolk) and carnitine (largely from red meat). Other GDUT are produced from amino acids, largely from meat consumption. Deficiency of vitamin B12 is very common, raises plasma tHcy, and is easily treated. However, cyanocobalamin is toxic in patients with renal failure. To reduce the risk of stroke in renal failure it is important to limit the intake of meat, avoid egg yolk, and use methylcobalamin instead of cyanocobalamin, in addition to folic acid.
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4.
Mitochondrion-driven nephroprotective mechanisms of novel glucose lowering medications.
Afsar, B, Hornum, M, Afsar, RE, Ertuglu, LA, Ortiz, A, Covic, A, van Raalte, DH, Cherney, DZI, Kanbay, M
Mitochondrion. 2021;:72-82
Abstract
Therapy for diabetic kidney disease (DKD) is undergoing a revolution with the realization that some glucose-lowering drugs have nephroprotective actions that may be intrinsic to the drugs and not dependent on the impact on diabetes control, as demonstrated with the sodium glucose co-transporter-2 (SGLT-2) inhibitors. Mitochondria are a critical factor required for the maintenance of kidney function, given its high energy demanding profile, with extensive use of adenosine triphosphate (ATP). Consequently, deficiency of the master regulator of mitochondrial biogenesis peroxisome proliferator-activated receptor gamma coactivator 1α predisposes to kidney disease. Perhaps as a result of key role of mitochondria in fundamental cellular functions, mitochondrial dysfunction may play a role in the pathogenesis of common conditions such as DKD. Finding pharmacological agents to influence this pathway could therefore lead to early implementation of therapy. Importantly, glucose-lowering drugs such as glucagon-like peptide-1 receptor activators and SGLT2 inhibitors have kidney and/or cardioprotective actions in patients with diabetes. Accumulating evidence from preclinical studies has suggested a protective effect of these drugs that is in part mediated by normalizing mitochondrial function. We now critically review this evidence and discuss studies needed to confirm mitochondrial protective benefits across a range of clinical studies.
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5.
Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? - A scoping review.
Nowroozpoor, A, Gutterman, D, Safdar, B
Microvascular research. 2021;:104123
Abstract
Although microvascular dysfunction (MVD) has been well characterized in individual organs as different disease entities, clinical evidence is mounting in support of an underlying systemic process. To address this hypothesis, we systematically searched PubMed and Medline for studies in adults published between 2014 and 2019 that measured blood biomarkers of MVD in three vital organs i.e. brain, heart, and the kidney. Of the 9706 unique articles 321 met the criteria, reporting 49 biomarkers of which 16 were common to the three organs. Endothelial dysfunction, inflammation including reactive oxidation, immune activation, and coagulation were the commonly recognized pathways. Triglyceride, C-reactive protein, Cystatin C, homocysteine, uric acid, IL-6, NT-proBNP, thrombomodulin, von Willebrand Factor, and uric acid were increased in MVD of all three organs. In contrast, vitamin D was decreased. Adiponectin, asymmetric dimethylarginine, total cholesterol, high-density and low-density cholesterol were found to be variably increased or decreased in studies. We review the pathways underlying MVD in the three organs and summarize evidence supporting its systemic nature. This scoping review informs clinicians and researchers in the multi-system manifestation of MVD. Future work should focus on longitudinal investigations to evaluate the multi-system involvement of this disease.
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6.
Metabolism of sugars: A window to the regulation of glucose and lipid homeostasis by splanchnic organs.
Tappy, L
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1691-1698
Abstract
BACKGROUND &AIMS: Dietary sugars are absorbed in the hepatic portal circulation as glucose, fructose, or galactose. The gut and liver are required to process fructose and galactose into glucose, lactate, and fatty acids. A high sugar intake may favor the development of cardio-metabolic diseases by inducing Insulin resistance and increased concentrations of triglyceride-rich lipoproteins. METHODS A narrative review of the literature regarding the metabolic effects of fructose-containing sugars. RESULTS Sugars' metabolic effects differ from those of starch mainly due to the fructose component of sucrose. Fructose is metabolized in a set of fructolytic cells, which comprise small bowel enterocytes, hepatocytes, and kidney proximal tubule cells. Compared to glucose, fructose is readily metabolized in an insulin-independent way, even in subjects with diabetes mellitus, and produces minor increases in glycemia. It can be efficiently used for energy production, including during exercise. Unlike commonly thought, fructose when ingested in small amounts is mainly metabolized to glucose and organic acids in the gut, and this organ may thus shield the liver from potentially deleterious effects. CONCLUSIONS The metabolic functions of splanchnic organs must be performed with homeostatic constraints to avoid exaggerated blood glucose and lipid concentrations, and thus to prevent cellular damages leading to non-communicable diseases. Excess fructose intake can impair insulin-induced suppression of glucose production, stimulate de novo lipogenesis, and increase intrahepatic and blood triglyceride concentrations. With chronically high fructose intake, enterocyte can switch to lipid synthesis and accumulation of triglyceride, possibly causing an enterocyte dysfunction.
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7.
Implications of Klotho Protein for Managing Kidney Disease - an Emerging Role in Therapeutics and Molecular Medicine.
Ray, SK, Masarkar, N, Mukherjee, S
Current molecular medicine. 2021;(6):484-494
Abstract
Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are a growing public health problem. There is a paucity of sensitive biomarkers to detect AKI, early CKD, and ameliorate extra-renal complications. Klotho protein, detected mainly in the kidneys, regulates renal health and functions as a co-receptor for fibroblast growth factor 23 (FGF-23) signaling. It is now coming to be known for its extreme pleiotropic actions. These include cytoprotection via anti-oxidation, anti-senescence, anti-apoptosis, renoprotective effects, promotion of angiogenesis and vascularisation, inhibition of fibrogenesis, and stem cell preservation. Emerging clinical studies suggest kidney damage to be a perpetual state of renal Klotho deficiency. In AKI, Klotho levels in plasma and/or urine possibly will serve as an initial biomarker for kidney parenchymal injury. In CKD, Klotho levels may also be an indicator of early disease as well as predict the rate of progression. Earlier studies using ELISA as a technique reveal a correlation between plasma Klotho, eGFR, serum creatine, and Blood Urea Nitrogen (BUN) levels. Thereby preventing the decline of Klotho levels by various mechanisms can retard CKD advancement and improve renal function. Substantial data indicate Klotho can be therapeutically included as an individualized regimen for managing CKD patients. Considerable research is required in investigating the role of soluble Klotho as a biomarker in patients with different types and severity of kidney diseases, which will be highlighted in our review.
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8.
Occupational heat exposure and the risk of chronic kidney disease of nontraditional origin in the United States.
Chapman, CL, Hess, HW, Lucas, RAI, Glaser, J, Saran, R, Bragg-Gresham, J, Wegman, DH, Hansson, E, Minson, CT, Schlader, ZJ
American journal of physiology. Regulatory, integrative and comparative physiology. 2021;(2):R141-R151
Abstract
Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.
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9.
[Contrast medium-induced acute kidney injury-Consensus paper of the working group "Heart and Kidney" of the German Cardiac Society and the German Society of Nephrology].
Latus, J, Schwenger, V, Schlieper, G, Reinecke, H, Hoyer, J, Persson, PB, Remppis, BA, Mahfoud, F
Der Internist. 2021;(1):111-120
Abstract
This consensus paper summarizes the expert consensus and recommendations of the working group "Heart and Kidney" of the German Cardiac Society (DGK) and the German Society of Nephrology (DGfN) on contrast medium-induced acute kidney injury. Potentially nephrotoxic contrast agents containing iodine are frequently used in interventional medicine and for computer tomography diagnostics. Acute kidney injury occurs in approximately 8-17% of patients exposed to contrast media. The risk factors and underlying pathophysiology are discussed and recommendations for the prophylaxis and treatment of contrast medium-induced acute nephropathy are presented.
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10.
High-Density Lipoproteins and the Kidney.
Strazzella, A, Ossoli, A, Calabresi, L
Cells. 2021;(4)
Abstract
Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin-cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.