Refining the Mouse Subtotal Nephrectomy in Male 129S2/SV Mice for Consistent Modeling of Progressive Kidney Disease With Renal Inflammation and Cardiac Dysfunction

Chronic kidney disease (CKD) is prevalent worldwide and is associated with significant co-morbidities including cardiovascular disease (CVD). Traditionally, the subtotal nephrectomy (remnant kidney) experimental model has been performed in rats to model progressive renal disease. The model experimentally mimics CKD by reducing nephron number, resulting in renal insufficiency. Presently, there is a lack of translation of pre-clinical findings into successful clinical results. The pre-clinical nephrology field would benefit from reproducible progressive renal disease models in mice in order to avail of more widely available transgenics and experimental tools to dissect mechanisms of disease. Here we evaluate if a simplified single step subtotal nephrectomy (STNx) model performed in the 129S2/SV mouse can recapitulate the renal and cardiac changes observed in patients with CKD in a reproducible and robust way. The single step STNx surgery was well-tolerated and resulted in clinically relevant outcomes including hypertension, increased urinary albumin:creatinine ratio, and significantly increased serum creatinine, phosphate and urea. STNx mice developed significant left ventricular hypertrophy without reduced ejection fraction or cardiac fibrosis. Analysis of intra-renal inflammation revealed persistent recruitment of Ly6Chi monocytes transitioning to pro-fibrotic inflammatory macrophages in STNx kidneys. Unlike 129S2/SV mice, C57BL/6 mice exhibited renal fibrosis without protein...
Source: Frontiers in Physiology - Category: Physiology Source Type: research

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Therapeutic Targeting of Fibrotic Epithelial-Mesenchymal Transition–An Outstanding Challenge Attila Fintha1, Ákos Gasparics2, László Rosivall3 and Attila Sebe3,4* 12nd Department of Pathology, Semmelweis University, Budapest, Hungary 21st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary 3Department of Pathophysiology, International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary 4Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany Back in 1995, a landmark paper was published, which shaped the fi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
CONCLUSIONS: The prevalence of adverse renal effects after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region, nephrectomy, or any combination of these, ranged from 0% to 84% depending on the study population, received treatment combination, reported outcome measure, follow-up duration and methodological quality. With currently available evidence, it was not possible to draw solid conclusions regarding the prevalence of, and treatment-related risk factors for, specific adverse renal effects. Future studies should focus on adequate study designs and reporting, including large pr...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
This study aimed to create a 1/16 remnant kidney model and to determine whether blood pressure (BP) control affects the progression of CKD. A group of dogs received BP treatment (group A) and another received BP treatment except for the first 2 weeks (group B). The remnant kidney model was induced using a two-step subtotal nephrectomy method; dogs received antihypertensive therapy. Systolic BP, blood urea nitrogen, serum creatinine, urinary protein, and creatinine levels were measured weekly. Kidney tissues were obtained at the conclusion of the study. Systolic BP was controlled to
Source: General Physiology and Biophysics - Category: Physiology Authors: Tags: Gen Physiol Biophys Source Type: research
Abstract Tetrahydrocurcumin (THC) is the principal metabolite of curcumin and has antioxidant properties. In the present investigation, the effect of THC on renal and cardiovascular outcomes was studied in rats with chronic kidney disease (CKD). CKD rats were randomized following 5/6 nephrectomy to a special diet for 9 weeks which contained 1% THC (CKD+THC group). Low‐dose polyenylphosphatidylcholine was used as a lipid carrier to increase bioavailability. Endpoints included tail blood pressure, normalized heart weight, plasma and urine biochemical data, and kidney tissue analyses. CKD animals demonstrated increased...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Abstract Chronic kidney disease (CKD) is a major health issue in the United States. The typical five-sixths nephrectomy (typical 5/6 NX) is a widely used experimental CKD model. However, the typical 5/6 NX model is hypertensive in rats, but strain dependent in mice. In particular, C57BL/6 mice with the typical 5/6 NX exhibits normal blood pressure and well-preserved renal function. The goal of the present study is to create a new hypertensive CKD model in C57BL/6 mice. We first characterized the vascular architecture originated from each renal artery branch by confocal laser scanning microscopy with fluorescent le...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
Authors: Jing W, Vaziri ND, Nunes A, Suematsu Y, Farzaneh T, Khazaeli M, Moradi H Abstract Progressive deterioration of kidney function in chronic kidney disease (CKD) is mediated by hypertension, oxidative stress, inflammation, and fibrosis. Renin-angiotensin blockade is commonly used to retard CKD progression. In addition, vasoactive peptides have been shown to reduce blood pressure and exert antioxidant, anti-inflammatory and anti-fibrotic effects. We hypothesized that administration of LCZ696 (sacubitril/valsartan) is more effective than valsartan alone in slowing progression of CKD. Male Sprague Dawley rats un...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Abstract Solitary functioning kidneys form an important subgroup of congenital anomalies of the kidney and urinary tract (CAKUT). A solitary kidney can be congenital or acquired after unilateral nephrectomy and is often associated with ipsilateral urogenital anomalies. Both types of solitary functioning kidney are associated with an increased risk of chronic kidney disease (CKD). A low functional nephron number results in compensatory glomerular hypertension and enlargement of remnant nephrons, indicating glomerular hyperfiltration. Glomerular hyperfiltration may lead to glomerulosclerosis, which further results i...
Source: Archives de Pediatrie - Category: Pediatrics Authors: Tags: Arch Pediatr Source Type: research
Abstract The consequences of live kidney donation on the donor health with main emphasis on postdonation blood pressure (BP), proteinuria, kidney size, and glomerular filtration rate (GFR) were evaluated. Twenty-five donors with minimum of six months postdonation duration were included in the study. Donor age at nephrectomy, duration postnephrectomy, systolic and diastolic BP measurement pre-and post-donation, postdonation, blood urea nitrogen, serum creatinine and 24-h proteinuria, blood sugar, two-dimensional echocardiogram were recorded. Kidney sizes pre-and post-donation were noted. GFR was calculated by chron...
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
Progressive fibrosis in chronic kidney disease (CKD) is the well-recognized cause leading to the progressive loss of renal function. Emerging evidence indicated a pathogenic role of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in mediating kidney injury. However, the role of NLRP3 in the remnant kidney disease model is still undefined. The present study was undertaken to evaluate the function of NLRP3 in modulating renal fibrosis in a CKD model of 5/6 nephrectomy (5/6 Nx) and the potential involvement of mitochondrial dysfunction in the pathogenesis. Employing NLRP3+/+ and NLRP3–/– m...
Source: AJP: Renal Physiology - Category: Urology & Nephrology Authors: Tags: ARTICLES Source Type: research
Authors: Tapia E, García-Arroyo F, Siverio O, Rodríguez-Alcocer AN, Jiménez-Flores AB, Cristobal M, Arellano AS, Soto V, Osorio-Alonso H, Molina-Jijón E, Pedraza-Chaverri J, Sanchez-Lozada LG Abstract Increased oxidative stress and inflammation have an important role in the pathophysiology of chronic kidney disease (CKD). On the other hand, more affordable therapeutic alternatives for treating this disease are urgently needed. Therefore, we compared the therapeutic efficacy of curcumin and mycophenolate mofetil (MMF) in 5/6 nephrectomy (5/6 Nx) model of CKD. Also, we evaluated whether bo...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research
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