Models of chronic kidney disease

Yang, Haichun; Zuo, Yiqin; Fogo, Agnes B.

doi:10.1016/j.ddmod.2010.08.002

Cited by 254 publications

(255 citation statements)

References 40 publications

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“…The 5/6 nephrectomized Sprague Dawley rat model mimics the progressive renal failure after loss of renal mass (19). Animals develop proteinuria and early glomerular hypertrophy during the acute phase (after 4 weeks), with increases in BUN.…”

Section: Discussionmentioning

confidence: 99%

“…The control (sham surgery) and 5/6 nephrectomized rats were used in these studies. Between 5 and 12 weeks, the 5/6 nephrectomized rats demonstrated increasing nephropathy with progressive albuminuria and rising ACR (18,19). At 10 weeks of age (with surgery performed at 5 weeks of age), the animals were dosed with 1 mg/kg of hIgG IV or SC (in the flank region).…”

Section: Methodsmentioning

confidence: 99%

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Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

Chadha

Morris

2015

AAPS J

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Abstract. The objective of this research was to assess the effects of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) on the pharmacokinetics of human IgG (hIgG), an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Furthermore, the specific role of T2DM in the altered disposition of hIgG was evaluated by treating diabetic rats with pioglitazone, while the role of chronic kidney disease (CKD) was assessed using 5/6 nephrectomized Sprague Dawley rats. ZDF male (lean non-diabetic control and obese diabetic) and pioglitazone-treated ZDF rats were studied at ages 12-13 weeks (only DM was present), and at ages 29-30 weeks (progression to DN). All animals were dosed with 1 mg/kg of hIgG intravenously (IV) or subcutaneously (SC). ZDF rats had significantly higher blood glucose concentrations and urinary albumin excretion compared to control rats. Significant increases in total clearance (2.5-fold) and renal clearance (100-fold) of hIgG were observed; however the major increase in total clearance was due to increased non-renal clearance. Greater changes in urinary albumin excretion and total and renal clearances of IgG (3.5-fold and 300-fold, respectively) were observed with progression to DN. SC bioavailability of hIgG in all animal groups was similar (>84%). With pioglitazone-treatment, diabetic animals remained euglycemic and treatment was able to reverse the clearance changes, although incompletely. In the CKD group, no difference in hIgG clearance was observed when compared with controls. In conclusion, the increased clearance of hIgG in ZDF diabetic animals, reversal by pioglitazone treatment and lack of effect of CKD, demonstrate the influence of T2DM on hIgG pharmacokinetics.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

Chadha

Morris

2015

AAPS J

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“…One week later (week 0), the intact right kidney was removed via a right flank incision, as previously described. 18,19 One week after the operation (week 1), the 5/6NX mice were randomized and divided into different groups (n Z 6 to 8 in each group): i) sham control; ii) 5/6NX mice injected with empty vector pcDNA3 (designated as 5/6NX group); and iii) 5/6NX mice injected with pV5-sKlotho plasmid (designated as 5/6NXþK group). In vivo expression of secreted Klotho in mice was performed by a hydrodynamic-based gene delivery approach, as described previously.…”

Section: Animal Modelsmentioning

confidence: 99%

Klotho Ameliorates Kidney Injury and Fibrosis and Normalizes Blood Pressure by Targeting the Renin-Angiotensin System

Zhou

Miao

et al. 2015

The American Journal of Pathology

140

117

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Loss of Klotho and activation of the renin-angiotensin system (RAS) are common pathological findings in chronic kidney diseases. However, whether these two events are intricately connected is poorly understood. We hypothesized that Klotho might protect kidneys by targeted inhibition of RAS activation in diseased kidneys. To test this hypothesis, mouse models of remnant kidney, as well as adriamycin nephropathy and unilateral ureteral obstruction, were utilized. At 6 weeks after 5/6 nephrectomy, kidney injury was evident, characterized by elevated albuminuria and serum creatinine levels, and excessive deposition of interstitial matrix proteins. These lesions were accompanied by loss of renal Klotho expression, up-regulation of RAS components, and development of hypertension. In vivo expression of exogenous Klotho through hydrodynamic-based gene delivery abolished the induction of multiple RAS proteins, including angiotensinogen, renin, angiotensin-converting enzyme, and angiotensin II type 1 receptor, and normalized blood pressure. Klotho also inhibited b-catenin activation and ameliorated renal fibrotic lesions. Similar results were obtained in mouse models of adriamycin and obstructive nephropathy. In cultured kidney tubular epithelial cells, Klotho dose-dependently blocked Wnt1-triggered RAS activation. Taken together, these results demonstrate that Klotho exerts its renal protection by targeted inhibition of RAS, a pathogenic pathway known to play a key role in the evolution and progression of hypertension and chronic kidney disorders. Chronic kidney disease (CKD) is increasingly recognized as a major public health problem, because it affects about 10% to 13% of the adult population worldwide.1e3 Among many risk factors for developing CKD, aging is an independent and strong predictor for progressive renal insufficiency. 4 The elderly population also tends to develop hypertension and cardiovascular disease, characteristic features consistent with the activation of the renin-angiotensin system (RAS). 5,6 These observations suggest that aging, CKD, and RAS activation might be intimately linked. However, the molecular details behind these connections are not fully understood.RAS consists of several key components, including angiotensinogen (AGT), renin, angiotensin-converting enzyme (ACE), and angiotensin II type I and type II receptors (AT1 and AT2, respectively).7e9 Two main enzymes in this system, renin and ACE, lead to the formation of angiotensin II, the principal active peptide of RAS, which mediates both blood pressureedependent and eindependent kidney damage in CKD. Several factors can induce RAS activation, such as reactive oxygen species, hyperglycemia, and albumin. 10,11 We recently found that all RAS genes contain T cell factor/ lymphoid enhancer-binding factor binding sites in their promoter regions and are directly regulated by canonical Wnt/ b-catenin signaling.12 These results have established that bcatenin is a master regulator controlling the expression of all RAS components in the kidneys.

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“…A full pharmacological importance of O. sanctum has been reviewed by Pattanayak et al [19]. O. sanctum is used in the siddha medicine for the treatment of nephrotic disorders [37,38].…”

Section: Resultsmentioning

confidence: 99%

Total Phenolic Content and Free Radical Scavenging Activity of Representative Medicinal Plants of Thailand

Chaiyasut

Kesika

Chaiyasut

et al. 2017

Asian J Pharm Clin Res

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Objective: Plants are the vital source of pharmaceutically important compounds with less or no adverse side effects. The current study was conducted to catalog the commonly used indigenous and medicinal plants of Thailand based on their phenolic acid content and antioxidant activity. Methods:The herbs were collected from Chiang Mai province, Thailand. The plants were extracted with 70% ethanol. The total phenolic acid content and antioxidant activity were evaluated. Results:The ethanolic extract of plant samples was prepared. Among the tested plant samples, Phyllanthus emblica Linn. and Terminalia belerica Roxb. showed highest phenolic content (Gallic acid equivalent [GAE]; 764.81 mg GAE/g sample) and antioxidant activity (trolox equivalent antioxidant capacity [TEAC]; 394.20 mg/g sample), respectively. About 94-97% of inhibition of free radical was detected in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay tested against the plant samples. The ethanolic extract of Anaxagorea luzonensis Gray., Terminalia sp., T. belerica Roxb, Terminalia chebula Retz., Albizia procera Benth., Harrisonia perforata Merr., and P. emblica Linn. exhibited 97.87, 96.08, 92.26, 86.74, 86.08, 84.47, and 83.13% of superoxide radical inhibition, respectively. Conclusion:The results suggested that T. belerica Roxb. possessed high TEAC ability and DPPH radical scavenging capacity and A. luzonensis Gray. exhibited high superoxide scavenging activity, when compared to that of the other tested samples. The additional detailed study is desirable to understand the complexity and distribution of bioactive compounds present in the commonly used plant species of Thailand.

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Models of chronic kidney disease

Cited by 254 publications

References 40 publications

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

Klotho Ameliorates Kidney Injury and Fibrosis and Normalizes Blood Pressure by Targeting the Renin-Angiotensin System

Total Phenolic Content and Free Radical Scavenging Activity of Representative Medicinal Plants of Thailand

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