Evaluation of Novel Urinary Renal Biomarkers with a Cisplatin Model of Kidney Injury: Effects of Collection Period

Pinches, Mark; Betts, Catherine J.; Bickerton, Sue; Beattie, Laura; Burdett, Lisa; Thomas, Helen T.; Derbyshire, Nicola; Moores, Michelle

doi:10.1177/0192623311432437

Cited by 20 publications

(15 citation statements)

References 23 publications

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“…Moreover, the relationship between the histopathological grade of glomerulonephropathy and our routine examination parameters remains unclear. We suggest that measuring sensitive biomarkers of glomerular injury such as plasma cystatin C, urinary b2-microglobulin, and kidney injury molecule-1 may facilitate the ability to judge the degree of progressive glomerulonephropathy in common marmosets (Pinches et al 2012a(Pinches et al , 2012b(Pinches et al , 2012c. …”

Section: Discussionmentioning

confidence: 99%

Morphological Study of Progressive Glomerulonephropathy in Common Marmosets (Callithrix jacchus)

et al. 2013

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Spontaneous progressive glomerulonephropathy often occurs in common marmosets. However, there are few detailed reports concerning the agerelated progressive process of glomerular changes. We discuss the glomerular changes in the early stage and the progressive changes in the advanced stage of nephropathy. We investigated the kidneys of common marmosets (2-11 years old; 9 males and 12 females) using hematoxylin and eosin, periodic acid-Schiff, periodic acid-methenamine-silver, and Masson's trichrome (MT) stains and a transmission electron microscope. There was no remarkable change in urine cytology, hematology, or blood chemistry. In the early stage of nephropathy, effacement of podocyte foot processes was observed ultrastructurally even though there were no marked glomerular lesions in the light microscopy. Subsequently, mesangial proliferation occurred from the hilar to peripheral side along the tuft. In the middle stage, red deposits were visible at the glomerular basement membrane (GBM) and the mesangial region directly under the GBM (paramesangial area) with the MT stain. Electron dense deposits were seen at the same area. In the advanced stage, the irregularity became prominent with or without dense deposits. It is necessary to investigate in detail whether the change of podocyte in the early stage was immuno-mediated or due to podocyte failure.

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Section: Discussionmentioning

confidence: 99%

Morphological Study of Progressive Glomerulonephropathy in Common Marmosets (Callithrix jacchus)

et al. 2013

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“…of MTX 2 days before the experiments was used (M360 2D, n = 4). The rats were placed in metabolic cages 24 hours before experiments without food to improve urine sample quality, as previously described, and with access to water ad libitum through urine collection periods. On the day of the experiment, urine was collected.…”

Section: Methodsmentioning

confidence: 99%

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

Severin

Campagno

Brandoni

et al. 2019

Clin Exp Pharma Physio

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Methotrexate (MTX) is commonly used in the treatment of malignant diseases and autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on the kidneys. Discovery of new biomarkers is required to improve the early detection of renal damage and optimize the effectiveness of treatments. The aim of this study was to evaluate the time course of MTX‐induced nephrotoxicity and to compare the urinary excretion of the organic anion transporter 5 (uOat5) with alterations in other markers of renal function, and to elucidate the possible molecular mechanisms involved in uOat5. Animals were exposed to a unique dose of MTX (80 mg/kg body weight, intraperitoneal). Experiments were carried out at days 2, 4, 8 or 14 after MTX administration. Markers of renal damage, such as creatinine and urea plasma levels, urinary activity of alkaline phosphatase, microalbuminuria, urinary excretion of neutrophil gelatinase‐associated lipocalin (uNGAL) and histopathology, were evaluated. Renal organic anion transporter 5 (Oat5) expression and its presence in different urine fraction were assessed by western blotting. uOat5 was significantly increased 2 days after MTX treatment, before than any alteration in other parameters of kidney injury or renal morphology occurred. uNGAL showed an inverted pattern of urinary excretion compared to uOat5. Exosomal pathway is involved in the urinary excretion of Oat5 and depends on the degree of damage induced by MTX. These experimental data allow proposing uOat5 as a potential non‐invasive biomarker for early detection of MTX‐induced nephrotoxicity.

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“…They can be species specific; thus, it is important to stress that they were evaluated only on rats. More information can be found elsewhere [ 100 , 122 , 123 , 181 – 183 ]. Recently, also urinary miRNA as noninvasive biomarker of AKI in humans [ 184 ] and rodents [ 185 ] was proposed.…”

Section: Challenges Of Cisplatin Rodent Modelmentioning

confidence: 99%

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Perše

Večerić-Haler

2018

BioMed Research International

178

140

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Cisplatin is an antitumor drug used in the treatment of a wide variety of malignancies. However, its primary dose-limiting side effect is kidney injury, which is a major clinical concern. To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed. Given the complex pathogenesis of kidney injury, which involves both local events in the kidney and interconnected and interdependent systemic effects in the body, cisplatin rodent model is indispensable in the investigation of underlying mechanisms and potential treatment strategies of both acute and chronic kidney injury. Cisplatin rodent model is well appreciated and widely used model due to its simplicity. It has many similarities to human cisplatin nephrotoxicity, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using cisplatin model. The present paper is aimed at giving a concise insight into the complex characteristics of cisplatin rodent model and heterogeneity of cisplatin dosage regimens as well as outlining factors that can severely influence the outcome of the model and the study. Challenges for future research are also mentioned.

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Evaluation of Novel Urinary Renal Biomarkers with a Cisplatin Model of Kidney Injury: Effects of Collection Period

Cited by 20 publications

References 23 publications

Morphological Study of Progressive Glomerulonephropathy in Common Marmosets (Callithrix jacchus)

Morphological Study of Progressive Glomerulonephropathy in Common Marmosets (Callithrix jacchus)

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

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