Intrarenal Renin–Angiotensin System Involvement in the Pathogenesis of Chronic Progressive Nephropathy—Bridging the Informational Gap Between Disciplines

Obert, Leslie; Frazier, Kendall S.

doi:10.1177/0192623319861367

Cited by 12 publications

(11 citation statements)

References 249 publications

(330 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CPN in mice comprises a wide spectrum of chronic degenerative renal lesions, including glomerulosclerosis, glomerular dilation, regressive changes and atrophy of tubules, increased connective tissue, and interstitial mononuclear cell infiltrates, the latter being especially common in mice. 19 In animals with advanced lesions including pelvic dilatation, the disease may constitute the major cause of death. 3 A doubled to tripled incidence of CPN has been reported in female mice versus males.…”

Section: Discussionmentioning

confidence: 99%

Causes of Mortality and Profile of Spontaneous Tumors in Young CD-1 Mice

Apreutese¹,

Levi²,

Taylor³

et al. 2022

Toxicol Pathol

View full text Add to dashboard Cite

A retrospective study was performed to establish the causes of mortality and incidence patterns of tumors in young (<50 weeks) control CD-1® mice from Charles River Laboratories. Tumor incidences (fatal and nonfatal) and nonneoplastic causes of death observed during the first 50 weeks of the study were collected from 48 thirteen-week toxicity studies conducted between 2009 and 2018 and from 43 carcinogenicity studies conducted between 2005 and 2018. Thirteen-week studies had a mortality rate of 8/620 (1.3%) in males and 4/620 (0.65%) in females. The major factors contributing to death were integument lesions in males (3/8) and experimental procedure–related injuries in females (3/4). All tumors recorded were nonfatal. Bronchiolo-alveolar adenoma was the commonest tumor with the same incidence in both males and females (4/620, 0.65%); a single lymphoma (0.16%) and uterine leiomyosarcoma (1/620 0.16%) were reported in females. The mortality rates of males and females that died or were euthanized during the first 50 weeks in carcinogenicity studies were 192/2830 (6.8%) and 198/2830 (7%), respectively. The most common fatal tumor in this age group was lymphoma in both sexes, with an incidence of 18/192 (9.3%) and 41/198 (20.7%) in males and females, respectively. In males tumors were responsible for fewer deaths than in females (17% vs. 32.3%). The major nonneoplastic causes of death or moribundity were cutaneous lesions (44/192, 22.9%), and obstructive uropathy (39/192, 20.3%) in males, and chronic progressive nephropathy (40/198, 20.2%) in females. Only minor differences were evident compared to a similar study performed 15 years ago; these might reflect changes in terminology and diagnostic criteria, and stricter animal welfare endpoints.

show abstract

Section: Discussionmentioning

confidence: 99%

Causes of Mortality and Profile of Spontaneous Tumors in Young CD-1 Mice

Apreutese¹,

Levi²,

Taylor³

et al. 2022

Toxicol Pathol

View full text Add to dashboard Cite

show abstract

“…On the other hand, vitamin D3 deficiency activates the local RAAS in the kidney, aggravating renal injury [63,64]. Intrarenal RAAS overactivation has been implicated in various animal models of renal disease as both an initial response and a driver for disease progression without increased plasma renin activity or plasma Ang II [65].…”

Section: Discussionmentioning

confidence: 99%

“…Based on the lack of association between systemic arterial hypertension and incidence of chronic progressive nephropathy [65], our study has illuminated the feasible crosstalk of the intrarenal RAAS overactivation and oxidative stress, inflammatory, and profibrotic signaling pathways, linking MetS to nephropathy progression independently of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D3 potentiates the nephroprotective effects of vildagliptin–metformin combination in a rat model of metabolic syndrome

Wahba

Abdel-Ghany

Ghareib

et al. 2021

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

The current study was conducted to investigate the nephroprotective effects of vildagliptin-metformin combination in an experimental model of fructose/ salt-induced metabolic syndrome (MetS). A major aim was to evaluate the potential capacity of vitamin D3 to potentiate the pleiotropic nephroprotective effects of vildagliptin-metformin combination. MetS was induced in adult male Wistar rats by adding fructose (10%) to everyday drinking water and salt (3%) to the diet for 6 weeks. Along with the same concentrations of fructose/salt feeding, MetS rats were then treated orally with either vildagliptin (10 mg/kg/day)-metformin (200 mg/kg/day) combination, vitamin D3 (10 μg/kg/day), or the triple therapy for a further 6 weeks. The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia, and impaired glucose tolerance. At the end of the 12-week experimental period, MetS rats displayed significantly deteriorated renal function, enhanced intrarenal oxidative stress and inflammation together with exaggerated renal histopathological damages and interstitial fibrosis. The study has corroborated antioxidant, anti-inflammatory, and antifibrotic effects of vildagliptinmetformin combination, vitamin D3, and the triple collaborative therapy, conferring renoprotection in the setting of MetS. Due attention has been paid to the crucial role of dipeptidyl peptidase-4 inhibition and sirtuin-1/5 0 adenosine monophosphate-activated protein kinase activation as novel therapeutic targets to optimize renoprotection. The apparent potentiating effect, evoked upon coadministration of vitamin D3 with vildagliptin-metformin combination, may provide a cornerstone for further clinical investigations.

show abstract

“…In a previous investigation of glomerular nephrin expression in Crl:CD(SD) rats with minimal change disease, nephrin expression was intact, although podocyte foot processes showed effacement under electron microscopy with no apparent morphological changes observed under light microscopy 18 . In the common renal disease of rats, chronic progressive nephropathy (CPN), it has been demonstrated that albuminuria accompanied by early-stage CPN may result in less changes in glomerular permeability from the failure to reabsorb albumin from proximal tubules 19 . In humans, there have been some investigations on the reduction of nephrin expression under minor changes 10 or under other kidney diseases 14,16 .…”

Section: Discussionmentioning

confidence: 99%

Morphological analyses of nephrin expression in progressive glomerulonephropathy of common marmosets

Yamada¹,

Doi²,

Sato³

et al. 2021

J Toxicol Pathol

View full text Add to dashboard Cite

In this study, we focused on nephrin, one of the key molecules within the slit diaphragm of podocytes, as although there have been reports on its expression in humans and rats, their presence in common marmosets has not been reported. We investigated nephrin expression and changes in glomeruli, depending on the development of spontaneous progressive glomerulonephropathy in common marmosets. Nineteen common marmosets at two to ten years of age were evaluated. The kidney was examined by microscopy with hematoxylin and eosin and immunohistochemical staining for nephrin. The lesions were classified into three grades according to a renal lesion grading system reported previously. The nephrin-positive area was measured by morphometric analysis, and the nephrin-positive ratio was calculated. Nephrin expression was observed along the glomerular capillary loop in a continuous linear pattern in renal lesion grades 0 to 2 and either discontinuous linear or coarse granular pattern in grade 3. Nephrin expression tended to decrease significantly depending on the grade of renal lesions. Alteration in nephrin expression has been suggested to play an important role in the progression of renal lesions.

show abstract

Intrarenal Renin–Angiotensin System Involvement in the Pathogenesis of Chronic Progressive Nephropathy—Bridging the Informational Gap Between Disciplines

Cited by 12 publications

References 249 publications

Causes of Mortality and Profile of Spontaneous Tumors in Young CD-1 Mice

Causes of Mortality and Profile of Spontaneous Tumors in Young CD-1 Mice

Vitamin D3 potentiates the nephroprotective effects of vildagliptin–metformin combination in a rat model of metabolic syndrome

Morphological analyses of nephrin expression in progressive glomerulonephropathy of common marmosets

Contact Info

Product

Resources

About