Did you mean: glomerulomegally
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American Journal of Physiology.... Jan 2023The prevalence of obesity has increased dramatically during the past decades, which has been a major health problem. Since 1975, the number of people with obesity... (Review)
Review
The prevalence of obesity has increased dramatically during the past decades, which has been a major health problem. Since 1975, the number of people with obesity worldwide has nearly tripled. An increasing number of studies find obesity as a driver of chronic kidney disease (CKD) progression, and the mechanisms are complex and include hemodynamic changes, inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system (RAAS). Obesity-related kidney disease is characterized by glomerulomegaly, which is often accompanied by localized and segmental glomerulosclerosis lesions. In these patients, the early symptoms are atypical, with microproteinuria being the main clinical manifestation and nephrotic syndrome being rare. Weight loss and RAAS blockers have a protective effect on obesity-related CKD, but even so, a significant proportion of patients eventually progress to end-stage renal disease despite treatment. Thus, it is critical to comprehend the mechanisms underlying obesity-related CKD to create new tactics for slowing or stopping disease progression. In this review, we summarize current knowledge on the mechanisms of obesity-related kidney disease, its pathological changes, and future perspectives on its treatment.
Topics: Humans; Renal Insufficiency, Chronic; Obesity; Renin-Angiotensin System; Glomerulosclerosis, Focal Segmental; Kidney Diseases; Chronic Disease; Kidney; Disease Progression
PubMed: 36383637
DOI: 10.1152/ajpendo.00179.2022 -
Diabetes, Metabolic Syndrome and... 2021Obesity-related glomerulopathy (ORG) is a secondary glomerular disease caused by obesity, with clinical manifestations such as proteinuria and glomerulomegaly.... (Review)
Review
Obesity-related glomerulopathy (ORG) is a secondary glomerular disease caused by obesity, with clinical manifestations such as proteinuria and glomerulomegaly. Currently, the high incidence of obesity brings a change in the spectrum of kidney diseases across the globe, including China. ORG has become another important secondary nephropathy leading to end-stage renal disease (ESRD), and its incidence has increased significantly. This trend is bound to bring about a serious socioeconomic burden. Therefore, it is urgent to study its pathogenesis and intervention measures. Currently, the occurrence and development mechanisms in ORG are complicated by many factors, which are still unclear. In the past 20 years, with the continuous intensive research on mechanisms such as hypoxia in the metabolic process, immune inflammation, and pyroptosis, there have been new advances in the mechanism of ORG, especially the important role of inflammation in podocyte injury and its impact on the progress of ORG. Here, we briefly review the possible pathogenic role of the inflammasome in the podocyte damage in ORG and summarize the possible therapeutical strategies targeting inflammasome.
PubMed: 34737593
DOI: 10.2147/DMSO.S334199 -
Best Practice & Research. Clinical... Jan 2014Adiponectin is a 30-kDa polypeptide secreted primarily by adipose tissue and plays a key role in kidney disease. In obesity, reduced adiponectin levels are associated... (Review)
Review
Adiponectin is a 30-kDa polypeptide secreted primarily by adipose tissue and plays a key role in kidney disease. In obesity, reduced adiponectin levels are associated with insulin resistance, cardiovascular disease and obesity related kidney disease. The latter includes microalbuminuria, glomerulomegaly, overt proteinuria and focal segmental glomerulosclerosis. Adiponectin levels in type 2 diabetics also negatively correlate with early features of nephropathy. However, in patients with established chronic kidney disease, adiponectin levels are elevated and positively predict progression of disease. The mechanism of action of adiponectin in the kidney appears to be related to AMPK activation and NADPH oxidase. Further studies are needed to elucidate this pathway and investigate the role of potential targets of adiponectin-AMPK-Nox pathway for CKD as obesity-related CKD is increasing worldwide.
Topics: AMP-Activated Protein Kinases; Adiponectin; Albuminuria; Amlodipine; Animals; Benzimidazoles; Benzoates; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Humans; Kidney; Kidney Diseases; Mice; Obesity; Oxidative Stress; Perindopril; Renal Insufficiency, Chronic; Telmisartan
PubMed: 24417947
DOI: 10.1016/j.beem.2013.08.002 -
Nephron 2021Obesity-related glomerulopathy (ORG) is an increasingly recognized cause of end-stage kidney disease. The most common clinical presentation is a slowly increasing... (Review)
Review
Obesity-related glomerulopathy (ORG) is an increasingly recognized cause of end-stage kidney disease. The most common clinical presentation is a slowly increasing nonnephrotic proteinuria that is followed by a progressive decline of kidney function. Key histological findings are glomerulomegaly and lesions of focal and segmental glomerulosclerosis. A central pathogenic mechanism is the increased sodium reabsorption by proximal tubules that typically accompanies obesity. This causes a decrease in the offer of sodium to the macula densa in the distal nephron, which results in a vasodilation of afferent glomerular arterioles and glomerular hyperfiltration. From a clinical point of view, it is essential to differentiate focal segmental glomerulosclerosis secondary to obesity from primary glomerular processes, which requires a careful differential diagnosis. Diet-induced weight loss, bariatric surgery, and renin-angiotensin blockers are the fundamental therapeutic measures in ORG. The recently developed sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonist represent a significant advance in renal protection and will probably improve clinical kidney outcomes in ORG.
Topics: Humans; Kidney Diseases; Kidney Glomerulus; Obesity; Risk Factors
PubMed: 33677441
DOI: 10.1159/000513868 -
Pflugers Archiv : European Journal of... Aug 2023Harboring apolipoprotein L1 (APOL1) variants coded by the G1 or G2 alleles of the APOL1 gene increases the risk for collapsing glomerulopathy, focal segmental... (Review)
Review
Harboring apolipoprotein L1 (APOL1) variants coded by the G1 or G2 alleles of the APOL1 gene increases the risk for collapsing glomerulopathy, focal segmental glomerulosclerosis, albuminuria, chronic kidney disease, and accelerated kidney function decline towards end-stage kidney disease. However, most subjects carrying APOL1 variants do not develop the kidney phenotype unless a second clinical condition adds to the genotype, indicating that modifying factors modulate the genotype-phenotype correlation. Subjects with an APOL1 high-risk genotype are more likely to develop essential hypertension or obesity, suggesting that carriers of APOL1 risk variants experience more pronounced insulin resistance compared to noncarriers. Likewise, arterionephrosclerosis (the pathological correlate of hypertension-associated nephropathy) and glomerulomegaly take place among carriers of APOL1 risk variants, and these pathological changes are also present in conditions associated with insulin resistance, such as essential hypertension, aging, and diabetes. Insulin resistance may contribute to the clinical features associated with the APOL1 high-risk genotype. Unlike carriers of wild-type APOL1, bearers of APOL1 variants show impaired formation of lipid droplets, which may contribute to inducing insulin resistance. Nascent lipid droplets normally detach from the endoplasmic reticulum into the cytoplasm, although the proteins that enable this process remain to be fully defined. Wild-type APOL1 is located in the lipid droplet, whereas mutated APOL1 remains sited at the endoplasmic reticulum, suggesting that normal APOL1 may participate in lipid droplet biogenesis. The defective formation of lipid droplets is associated with insulin resistance, which in turn may modulate the clinical phenotype present in carriers of APOL1 risk variants.
Topics: Humans; Apolipoprotein L1; Insulin Resistance; Genotype; Hypertension, Renal; Essential Hypertension
PubMed: 37261508
DOI: 10.1007/s00424-023-02821-z -
Frontiers in Medicine 2021Incidence of obesity related renal disorders have increased 10-folds in recent years. One of the consequences of obesity is an increased glomerular filtration rate (GFR)... (Review)
Review
Incidence of obesity related renal disorders have increased 10-folds in recent years. One of the consequences of obesity is an increased glomerular filtration rate (GFR) that leads to the enlargement of the renal glomerulus, i.e., glomerulomegaly. This heightened hyper-filtration in the setting of type 2 diabetes irreparably damages the kidney and leads to progression of end stage renal disease (ESRD). The patients suffering from type 2 diabetes have progressive proteinuria, and eventually one third of them develop chronic kidney disease (CKD) and ESRD. For ameliorating the progression of CKD, inhibitors of renin angiotensin aldosterone system (RAAS) seemed to be effective, but on a short-term basis only. Long term and stable treatment strategies like weight loss via restricted or hypo-caloric diet or bariatric surgery have yielded better promising results in terms of amelioration of proteinuria and maintenance of normal GFR. Body mass index (BMI) is considered as a traditional marker for the onset of obesity, but apparently, it is not a reliable indicator, and thus there is a need for more precise evaluation of regional fat distribution and amount of muscle mass. With respect to the pathogenesis, recent investigations have suggested perturbation in fatty acid and cholesterol metabolism as the critical mediators in ectopic renal lipid accumulation associated with inflammation, increased generation of ROS, RAAS activation and consequential tubulo-interstitial injury. This review summarizes the renewed approaches for the obesity assessment and evaluation of the pathogenesis of CKD, altered renal hemodynamics and potential therapeutic targets.
PubMed: 34268323
DOI: 10.3389/fmed.2021.673556 -
Nephron 2015For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than... (Review)
Review
For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than explain this nephrovasculopathy. Hypertensive nephrosclerosis was long considered a major cause of end-stage renal failure (ESRD). This is especially true in blacks of African descent but not in other ethnic populations. The term 'nephrosclerosis' is still an easy way out to classify a patient with renal insufficiency. This leads to neglect the possibility of an overlooked nephropathy complicated by hypertension and to believe that drastic blood pressure control may retard the progression to ESRD. Several clinical and experimental lines of evidence lead to the understanding that nephrosclerosis, especially in blacks, is a genetic renovasculopathy that precedes the rise in blood pressure. The identification of coding region variants in APOL1 encoding apolipoprotein L-1 in black but also white and Asians opens new lines of research on the genetics of nephroangiosclerosis and of FSGS. Metabolic derangements, such as obesity, oxidative stress, dyslipidemia and atherosclerosis may be considered confounding factors with regard to nephrosclerosis. Histomorphometric studies led to sorting out the lesions due to aging from those stemming from hypertension. They shed new light not only on glomerular lesions that comprise ischemic obsolescence but also on glomerulomegaly and focal-segmental sclerosis, the latter due to a loss of renal autoregulation. It appears that the control of hypertension is not credited with the expected benefit for slowing the decline of renal function. 'Nephrosclerosis' can be considered an umbrella term of poor significance that should be replaced by its pathologic description, that is, arterionephrosclerosis and incite to elucidate the various genetic and metabolic factors that lead to a lesion in quest of a specific disease.
Topics: Humans; Hypertension; Nephrosclerosis; Risk Factors; Terminology as Topic
PubMed: 25871843
DOI: 10.1159/000381195 -
Scientific Reports Apr 2023Obesity-related glomerulopathy and diabetic nephropathy (DN) are serious complications to metabolic syndrome and diabetes. The purpose was to study effects of a fat,...
Obesity-related glomerulopathy and diabetic nephropathy (DN) are serious complications to metabolic syndrome and diabetes. The purpose was to study effects of a fat, fructose and cholesterol-rich (FFC) diet with and without salt in order to induce hypertension on kidney function and morphology in Göttingen Minipigs with and without diabetes. Male Göttingen Minipigs were divided into 4 groups: SD (standard diet, n = 8), FFC (FFC diet, n = 16), FFC-DIA (FFC diet + diabetes, n = 14), FFC-DIA + S (FFC diet with extra salt + diabetes, n = 14). Blood and urine biomarkers, glomerular filtration rate (GFR), blood pressure (BP) and resistive index (RI) were evaluated after 6-7 months (T1) and 12-13 months (T2). Histology, electron microscopy and gene expression (excluding FFC-DIA + S) were evaluated at T2. All groups fed FFC-diet displayed obesity, increased GFR and RI, glomerulomegaly, mesangial expansion (ME) and glomerular basement membrane (GBM) thickening. Diabetes on top of FFC diet led to increased plasma glucose and urea and proteinuria and tended to exacerbate the glomerulomegaly, ME and GBM thickening. Four genes (CDKN1A, NPHS2, ACE, SLC2A1) were significantly deregulated in FFC and/or FFC-DIA compared to SD. No effects on BP were observed. Göttingen Minipigs fed FFC diet displayed some of the renal early changes seen in human obesity. Presence of diabetes on top of FFC diet exacerbated the findings and lead to changes resembling the early phases of human DN.
Topics: Animals; Swine; Male; Humans; Diabetic Nephropathies; Swine, Miniature; Kidney; Obesity; Glomerular Basement Membrane; Diabetes Mellitus
PubMed: 37045950
DOI: 10.1038/s41598-023-32674-6 -
Seminars in Nephrology Jul 2021The kidney is one of the target organs that may show health disorders as a result of obesity. Obesity-related glomerulopathy (ORG) is a kidney disease category based on... (Review)
Review
The kidney is one of the target organs that may show health disorders as a result of obesity. Obesity-related glomerulopathy (ORG) is a kidney disease category based on a biopsy diagnosis that may occur secondary to obesity. Detailed clinicopathologic observations of ORG have provided significant knowledge regarding obesity-associated renal complications. Glomerulomegaly with focal segmental glomerulosclerosis of perihilar locations is a typical renal histopathologic finding in ORG, which has long been considered to represent a state of single-nephron glomerular hyperfiltration. This hypothesis was recently confirmed in ORG patients by estimating single-nephron glomerular filtration rate using a combined image analysis and biopsy-based stereology. Overshooting in glomerulotubular and tubuloglomerular interactions may lead to glomerular hyperfiltration/hypertension, podocyte failure, tubular protein-traffic overload, and tubulointerstitial scarring, constituting a vicious cycle of a common pathway to the further loss of functioning nephrons and the progression of kidney functional impairment.
Topics: Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Kidney; Kidney Glomerulus; Obesity; Podocytes
PubMed: 34715960
DOI: 10.1016/j.semnephrol.2021.06.002 -
Nefrologia : Publicacion Oficial de La... 2011Obesity is associated with the early onset of glomerulomegaly, hemodynamic changes of a hyperfiltering kidney, and increased albuminuria, which are potentially... (Review)
Review
Obesity is associated with the early onset of glomerulomegaly, hemodynamic changes of a hyperfiltering kidney, and increased albuminuria, which are potentially reversible with weight loss. However, pathologic lesions of focal segmental glomerulosclerosis develop in experimental models of sustained obesity, and are observed in morbidly obese humans presenting with massive proteinuria. In addition, several observational, cross sectional and longitudinal studies document that obesity is as an independent risk factor for the onset, aggravated course, and poor outcomes of chronic kidney disease, even after adjustment for confounding co-morbidities including metabolic syndrome, diabetes and hypertension, the major causes of chronic kidney disease. Early dietary intervention to reduce weight, and where necessary bariatric surgery, should be considered in the management of overweight and obese chronic kidney disease (CKD) patients.
Topics: Cardiovascular Diseases; Chronic Disease; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Diabetes Mellitus; Disease Progression; Follow-Up Studies; Humans; Hypertension; Insulin Resistance; Kidney; Kidney Diseases; Obesity; Prognosis; Proteinuria; Renal Circulation; Renal Dialysis; Risk Factors; Weight Loss
PubMed: 21623393
DOI: 10.3265/Nefrologia.pre2011.May.10963