Transcutaneous Assessment of Renal Function in Conscious Rodents

Pérez, Zeneida Herrera; Weinfurter, Stefanie; Gretz, Norbert

doi:10.3791/53767-v

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…GFR was measured by transdermal analysis using the fluorescein isothiocyanate–sinistrin method. 21 Briefly, animals under anesthesia were shaved on the dorsal side and the optical device (Transdermal Mini GFR Monitor, MediBeacon) attached to measure fluorescein isothiocyanate–sinistrin clearance as an estimate of GFR, as described below. Background readings were recorded for 3 minutes before administration of the sinistrin (7 mg/100 g bodyweight bolus).…”

Section: Methodsmentioning

confidence: 99%

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease

Lima Posada,

Soulié,

Stephan

et al. 2024

JAHA

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Background The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO‐DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO‐DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes. Methods and Results We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD‐related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short‐term finerenone treatment decreased LV end‐diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity. Conclusions We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.

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Section: Methodsmentioning

confidence: 99%

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease

Lima Posada,

Soulié,

Stephan

et al. 2024

JAHA

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show abstract

“…SCr and blood urea nitrogen (BUN) concentrations were tested using the QuantiChrom Creatinine or Urea Assay Kit (BioAssay Systems, Hayward, CA, USA). Subsequently, the transcutaneous GFR was measured with FITC-conjugated sinistrin (MediBeacon, Inc, Mannheim, Germany) (25). Briefly, after anesthesia, a miniaturized imaging device with two light-emitting diodes (MediBeacon, Inc, Mannheim, Germany) was taped to the cleaned lank back.…”

Section: Methodsmentioning

confidence: 99%

A Novel Rat Model of Contrast-Induced Acute Kidney Injury Based on Renal Congestion and the Reno-Protection of Mitochondrial Fission Inhibition

Yang

Ning

et al. 2023

Shock

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Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication in patients receiving intravenous iodinated contrast medium (CM). Clinically, congestive heart failure is the most critical risk factor for CI-AKI and always leads to renal congestion for increased central venous pressure and fluid overload. Here, we aimed to investigate a novel CI-AKI rat model based on renal congestion. After the exploratory testing phase, we successfully constructed a CI-AKI rat model by inducing renal congestion by clamping the unilateral renal vein, removing the contralateral kidney, and a single tail vein injection of iohexol. This novel CI-AKI rat model showed elevated serum creatinine, urea nitrogen, and released tubular injury biomarkers (KIM-1 and NGAL), reduced glomerular filtration rate, and typical pathologic features of CM-induced tubular injury with extensive foamy degeneration, tubular edema, and necrosis. Electron microscopy and confocal laser scanning revealed excessive mitochondrial fission and increased translocation of Drp1 from the cytoplasm to the mitochondrial surface in tubular epithelial cells. As a Drp1 inhibitor, Mdivi-1 attenuated excessive mitochondrial fission and exerted reno-protection against CM injury. Simultaneously, Mdivi-1 alleviated oxidative stress, apoptosis, and inflammatory responses induced by CM toxicity. We concluded that renal congestion exacerbated CM toxicity and presented a novel CI-AKI rat model. Excessive mitochondrial fission plays a crucial role in CM reno-toxicity and is a promising target for preventing and treating CI-AKI.

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Activation of renal vascular smooth muscle TRPV4 channels by 5-hydroxytryptamine impairs kidney function in neonatal pigs

Afolabi

Michael

Falayi

et al. 2023

Microvascular Research

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Transcutaneous Assessment of Renal Function in Conscious Rodents

Cited by 3 publications

References 13 publications

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease

A Novel Rat Model of Contrast-Induced Acute Kidney Injury Based on Renal Congestion and the Reno-Protection of Mitochondrial Fission Inhibition

Activation of renal vascular smooth muscle TRPV4 channels by 5-hydroxytryptamine impairs kidney function in neonatal pigs

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