Correlation Between Cyclosporine-Induced Nephrotoxicity in Reduced Nephron Mass and Expression of Kidney Injury Molecule-1 and Aquaporin-2 Gene

Hong, Mauricio; Hong, Jeong-Ah; Stepkowski, S. M.; Kahan, Barry D.

doi:10.1016/j.transproceed.2005.10.025

Cited by 16 publications

(11 citation statements)

References 22 publications

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“…We found no statistically significant differences in the concentration of renal injury markers between control group and all treatment groups, but we observed higher levels of NGAL in dams from CMG and TMG group in comparison to dams from CEG group. Data from previous studies revealed increased expression of KIM-1 in rat kidney in a model of cyclosporine-induced nephrotoxicity [ 5 , 24 ]. Tacrolimus up-regulated renal cortical gene for MCP-1 [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats

et al. 2016

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Pregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone). The animals received drugs for 2 weeks before pregnancy and during 3 weeks of pregnancy. In all treated dams lower body weight (but not kidney mass) and alterations in serum sodium and chloride ions were found; serum creatinine concentration was increased in dams treated with cyclosporine A, everolimus and prednisone. All treatment groups of dams showed increased apoptosis in the distal tubules. In histological examination the changed intensity of acidophilic or basophilic cytoplasm of epithelial cells was found in kidneys of rats treated with calcineurin inhibitors, mycophenolate mofetil and prednisone. All immunosuppressive regimens caused abnormalities affecting nephron tubules. Regimens containing calcineurin inhibitors and mycophenolate mofetil caused higher rate of apoptosis and more pronounced histopathological changes. Regimen based on everolimus despite the lower rate of apoptosis in the proximal tubules and lower accumulation of kidney injury markers revealed higher serum creatinine concentration. Thus, interpretation which combination of drugs is better or worse for long-lasting functioning of kidneys in pregnant females requires further studies.

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Section: Discussionmentioning

confidence: 99%

The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats

et al. 2016

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“…The Kim-1 ectodomain is stable in urine and can be detected in the kidney and urine in humans with acute renal injury (Han & Bonventre, 2004), and in a variety of animal models of nephrotoxic injury (Amin et al, 2004;Ichimura et al, 2004;Vaidya et al, 2006). Some of the drugs/chemicals that have been examined in this context, and for which Kim-1 appears to be a sensitive marker of renal injury include: cisplatin, S-(1,1,2,2,-tetrafluorethyl)-L-cysteine, folic acid (Ichimura et al, 2004;Vaidya et al, 2006), cyclosporine (Hong et al, 2005;Perez-Rojas et al, 2006), Hg (Goering et al, 2006) and Cd (Prozialeck et al, 2006c).…”

Section: Kidney Injury Molecule-1mentioning

confidence: 99%

Cell adhesion molecules in chemically-induced renal injury

Prozialeck

Edwards

2007

Pharmacology & Therapeutics

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Cell adhesion molecules are integral cell-membrane proteins that maintain cell-cell and cell-substrate adhesion and in some cases act as regulators of intracellular signaling cascades. In the kidney, cell adhesion molecules, such as the cadherins, the catenins, the zonula occludens protein-1 (ZO-1), occludin and the claudins are essential for maintaining the epithelial polarity and barrier integrity that are necessary for the normal absorption/excretion of fluid and solutes. A growing volume of evidence indicates that these cell adhesion molecules are important early targets for a variety of nephrotoxic substances including metals, drugs, and venom components. In addition, it is now widely appreciated that molecules, such as intracellular adhesion molecule-1 (ICAM-1), integrins, and selectins play important roles in the recruitment of leukocytes and inflammatory responses that are associated with nephrotoxic injury. This review summarizes the results of recent in vitro and in vivo studies indicating that these cell adhesion molecules may be primary molecular targets in many types of chemically-induced renal injury. Some of the specific agents that are discussed include cadmium (Cd), mercury (Hg), bismuth (Bi), cisplatin, aminoglycoside antibiotics, S-(1,2-dichlorovinyl)-l-cysteine (DCVC), and various venom toxins. This review also includes a discussion of the various mechanisms, by which these substances can affect cell adhesion molecules in the kidney.

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“…The hepatitis A virus cellular receptor 1 (HAVCR1), also known as kidney injury molecule‐1 (Kim‐1), was reported to be highly upregulated in kidney tissue in response to various nephrotoxins suggesting a possible role of Kim‐1 as a biomarker for renal injury [43,44]. Vaidya et al [45] used a sandwich ELISA to detect the amount of urinary Kim‐1 in order to assess early kidney injury.…”

Section: Molecular Biomarkers Of Ischemia Reperfusion Injurymentioning

confidence: 99%

Gene expression and biomarkers in renal transplant ischemia reperfusion injury

et al. 2007

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Summary The incidence of postischemic acute renal allograft failure (ARF) occurs in roughly 25% of cadaveric donor kidney recipients. This high rate remained virtually unchanged over the last decades despite modification in recipient management and modern immunosuppressive strategies. It has recently been shown that among other reasons, the systemic inflammation in the brain death cadaveric organ donor contributes to subsequent ARF in the recipient. This review focuses on the consequences of ischemia and reperfusion on the cellular level and offers potential solutions for the reduction of ARF. Genome‐wide gene expression analysis together with sophisticated biostatistical analysis made it possible to identify several candidate gene products and proteins that may act as specific and sensitive biomarker for renal inflammation and ischemia. These markers may be very helpful in the clinical management of patients with a high a priori risk of subsequent ARF such as recipients of marginal donor kidneys. Ongoing clinical trials will evaluate whether immunosuppression of the cadaveric organ donor before organ harvest will have the potential to reduce inflammation in the transplant kidney and subsequently lead to a reduction in the rate of ARF.

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Correlation Between Cyclosporine-Induced Nephrotoxicity in Reduced Nephron Mass and Expression of Kidney Injury Molecule-1 and Aquaporin-2 Gene

Cited by 16 publications

References 22 publications

The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats

The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats

Cell adhesion molecules in chemically-induced renal injury

Gene expression and biomarkers in renal transplant ischemia reperfusion injury

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