Transcutaneous Measurement of Glomerular Filtration Rate in Rodents

Daniele, Cristina; Nardozi, Daniela; Torelli, Angelo; Khan, Arif ul Maula; Gretz, Norbert

doi:10.1007/978-1-4939-9841-8_9

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…The measurement was performed for at least 2 hours, during which the animal was completely awake and freely moving. Half-life excretion of the administered ABZWCY-HPβCD was calculated based on a 3-compartment model using the open source freely-available software ‘GFR measure’ ( https://www.mathworks.com/products/compiler/matlab-runtime.html ) ( 28 ).…”

Section: Methodsmentioning

confidence: 99%

Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert anti-apoptotic and anti-inflammatory effects in vitro and modulate mRNA expression in a cisplatin-induced kidney injury murine model

Rendra,

Crigna,

Daniele

et al. 2024

Front. Immunol.

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Acute kidney injury (AKI) is characterized by a rapid reduction in renal function and glomerular filtration rate (GFR). The broadly used anti-cancer chemotherapeutic agent cisplatin often induces AKI as an adverse drug side effect. Therapies targeted at the reversal of AKI and its potential progression to chronic kidney disease or end-stage renal disease are currently insufficiently effective. Mesenchymal stromal cells (MSCs) possess diverse immunomodulatory properties that confer upon them significant therapeutic potential for the treatment of diverse inflammatory disorders. Human dermal MSCs expressing ATP-Binding Cassette member B5 (ABCB5) have shown therapeutic efficacy in clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. In preclinical studies, ABCB5+ MSCs have also shown to reverse metabolic reprogramming in polycystic kidney cells, suggesting a capacity for this cell subset to improve also organ function in kidney diseases. Here, we aimed to explore the therapeutic capacity of ABCB5+ MSCs to improve renal function in a preclinical rat model of cisplatin-induced AKI. First, the anti-apoptotic and immunomodulatory capacity was compared against research-grade adipose stromal cells (ASCs). Then, cross-species immunomodulatory capacity was checked, testing first inhibition of mitogen-driven peripheral blood mononuclear cells and then modulation of macrophage function. Finally, therapeutic efficacy was evaluated in a cisplatin AKI model. First, ABCB5+ MSCs suppressed cisplatin-induced apoptosis of human conditionally-immortalized proximal tubular epithelial cells in vitro, most likely by reducing oxidative stress. Second, ABCB5+ MSCs inhibited the proliferation of either human or rat peripheral blood mononuclear cells, in the human system via the Indoleamine/kynurenine axis and in the murine context via nitric oxide/nitrite. Third, ABCB5+ MSCs decreased TNF-α secretion after lipopolysaccharide stimulation and modulated phagocytosis and in both human and rat macrophages, involving prostaglandin E2 and TGF-β1, respectively. Fourth, clinical-grade ABCB5+ MSCs grafted intravenously and intraperitoneally to a cisplatin-induced AKI murine model exerted modulatory effects on mRNA expression patterns toward an anti-inflammatory and pro-regenerative state despite an apparent lack of amelioration of renal damage at physiologic, metabolic, and histologic levels. Our results demonstrate anti-inflammatory and pro-regenerative effects of clinical grade ABCB5+ MSCs in vitro and in vivo and suggest potential therapeutic utility of this cell population for treatment or prevention of cisplatin chemotherapy-induced tissue toxicity.

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Section: Methodsmentioning

confidence: 99%

Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert anti-apoptotic and anti-inflammatory effects in vitro and modulate mRNA expression in a cisplatin-induced kidney injury murine model

Rendra,

Crigna,

Daniele

et al. 2024

Front. Immunol.

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“…The NIC-Kidney device (Mannheim Pharma & Diagnostics GmbH, Mannheim, Germany) was attached to the shaved back of each animal. After a few minutes for collection of baseline values, fluorescein isothiocyanate–labeled sinistrin (7.5 mg/100 g) was injected via the tail vein, and tGFR was calculated based on the kinetics of fluorescence decay ( 33 , 34 ).…”

Section: Methodsmentioning

confidence: 99%

Cardiac-specific renalase overexpression alleviates CKD-induced pathological cardiac remodeling in mice

Wang

Bai

Wen

et al. 2022

Front. Cardiovasc. Med.

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IntroductionCKD-induced pathological cardiac remodeling is characterized by myocardial hypertrophy and cardiac fibrosis. The available therapeutic options are limited, it is thus urgently needed to identify novel therapeutic targets. Renalase (RNLS) is a newly discovered protein secreted by the kidney and was found beneficial in many renal diseases. But whether it exerts protective effects on cardiac remodeling in CKD remains unclear.MethodsRNLS knockout (KO) and wild-type (WT) mice were both used to build CKD models and the adeno-associated virus (AAV9) system was used to overexpress RNLS cardiac specifically. Echocardiography was performed to detect cardiac structural changes every 6 weeks until 18 weeks post-surgery. High throughput sequencing was performed to understand the underlying mechanisms and the effects of RNLS on cardiac fibroblasts were validated in vitro.ResultsKnockout of RNLS aggravated cardiac remodeling in CKD, while RNLS cardiac-specific overexpression significantly reduced left ventricular hypertrophy and cardiac fibrosis induced by CKD. The following RNA-sequencing analysis revealed that RNLS significantly downregulated the extracellular matrix (ECM) receptor interaction pathway, ECM organization, and several ECM-related proteins. GSEA results showed RNLS significantly downregulated several profibrotic biological processes of cardiac fibroblasts which were upregulated by CKD, including fibroblast proliferation, leukocyte migration, antigen presentation, cytokine production, and epithelial-mesenchymal transition (EMT). In vitro, we validated that RNLS reduced the primary cardiac fibroblast proliferation and α-SMA expression stimulated by TGF-β.ConclusionIn this study, we examined the cardioprotective role of RNLS in CKD-induced cardiac remodeling. RNLS may be a potential therapeutic factor that exerts an anti-fibrotic effect in pathological cardiac remodeling.

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“…The ABZWCY-HPβCD and AAZWCY-HPβCD fluorescent probes absorb at around 704 nm and emit at around 790 nm in plasma, with a Stoke's shift of roughly 86 nm. This allows deeper tissue penetration and easier transcutaneous measurement [2,26]. Similarly, Cy7.5 dye is used to label carboxymethyl inulin (CMI) to image the NIR-GFR marker using a transcutaneous pulse dye densitometer (TPDD) [27].…”

Section: Gfr Markersmentioning

confidence: 99%

“…The data from the device is recorded for a baseline (without dye) after which FITC-S is injected intravenously. A modified version of this device has been developed using NIR LEDs, which uses ABZWCY-HPβCD that has an emission maximum at 790 nm [26].…”

Section: Non-invasive Measurement Techniquesmentioning

confidence: 99%

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An overview of non-invasive methods for transcutaneous measurements of glomerular filtration

Yusuf

Picascia

Vajpayee

et al. 2021

Journal of Experimental Nephrology

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Chronic kidney disease (CKD) affects 10% of the population worldwide. It often leads to poor quality of life, especially among people suffering from end-stage CKD. Detection and treatment of the renal disorders at an early stage can help in postponing of end-stage disease as well as its treatment options, such as renal transplant and dialysis. The current routine measurement of glomerular filtration rate (GFR) includes methods that are expensive, cumbersome, time-consuming, inaccurate, often inconvenient and invasive for the patients. Non-invasive diagnostic techniques can help to overcome many of these drawbacks. This paper reviews the progress made in the field of transcutaneous GFR measurement as a way for a simpler, non-invasive, cheaper, and patient-friendly assessment of renal function. We have discussed the various markers designed in combination with different measurement devices for the measurement of GFR. Also, we have compared the different kinetic models used to study the marker's clearance from the plasma; which ultimately helps in calculating the GFR. Most of these techniques have been limited to pre-clinical studies until now, with promising results for their transition into clinical use in the near future.

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Transcutaneous Measurement of Glomerular Filtration Rate in Rodents

Cited by 5 publications

References 14 publications

Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert anti-apoptotic and anti-inflammatory effects in vitro and modulate mRNA expression in a cisplatin-induced kidney injury murine model

Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert anti-apoptotic and anti-inflammatory effects in vitro and modulate mRNA expression in a cisplatin-induced kidney injury murine model

Cardiac-specific renalase overexpression alleviates CKD-induced pathological cardiac remodeling in mice

An overview of non-invasive methods for transcutaneous measurements of glomerular filtration

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