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      Imaging Acute Renal Failure with Polyamine Dendrimer-Based MRI Contrast Agents


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          Acute renal failure (ARF) induced by sepsis has a high mortality but lacks effective treatments. To develop novel therapies we must diagnose renal injury early and accurately in septic patients and identify any additional insults such as nephrotoxic drugs and ischemia. In this short review we describe our experience using MRI with dendrimer-based contrast agents in mouse models of ARF. This technique can diagnose early renal injury before serum creatinine is elevated, distinguish different ARF etiologies, track drug therapy and predict outcome. As an ARF biomarker, MRI with dendrimer-based contrast is a promising technique deserving further development.

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          Most cited references14

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          Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome.

          Acute renal failure (ARF) is a common complication in intensive care unit (ICU) patients. Although there are several reports on outcome of septic patients with ARF, there are no data regarding predisposing factors for ARF. Therefore, the incidence of ARF was investigated in 185 sepsis patients admitted in a surgical ICU during a 16-mo period. Variables predisposing to ARF on day 1 of sepsis were evaluated with univariate and multivariable analyses. APACHE II and SOFA scores were compared during a 14-d period. Additionally, the impact of organ failure on mortality was evaluated. ARF developed in 16.2% of the patients, and 70.0% of these needed renal replacement therapy (RRT). Patients with ARF were more severely ill and had a higher mortality. Remarkably, serum creatinine was already increased on day 1. Creatinine > 1 mg/dl and pH < 7.30, both on day 1 of sepsis, were independently associated with ARF. Age, need for vasoactive therapy, mechanical ventilation, and RRT, but not ARF itself, were associated with mortality. In conclusion, ARF was a frequent complication in sepsis. Sepsis patients with ARF were more severely ill and had a higher mortality. Need for RRT was independently associated with mortality. A simple risk model for ARF, on basis of two readily available parameters on day 1 of sepsis, was developed. This model allows initiating specific therapeutic measures earlier in the course of sepsis, hopefully resulting in a lower incidence of ARF and needi for RRT, thereby lowering mortality.
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            Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor.

            The authors developed a new method for delivering contrast agents to tumors and tumor cells. Gadolinium complexes of folate-conjugated dendrimer-chelates increased the longitudinal relaxation rate of tumor cells expressing the high-affinity folate receptor, hFR. The coupling of folate to polymeric chelates, composed of a dendrimer backbone, targets these chelates to endogenous folate binding proteins. These proteins exist in both the serum of patients with cancer and on the cell surface of many human cancers of epithelial origin.
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              Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats.

              Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                March 2006
                10 March 2006
                : 103
                : 2
                : c45-c49
                aRenal Diagnostics and Therapeutics Unit, NIDDK, bMolecular Imaging Program, Center for Cancer Research, NCI, and cRadioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Md., USA
                90608 Nephron Clin Pract 2006;103:c45–c49
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 4, References: 23, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/90608
                Self URI (text/html): https://www.karger.com/Article/FullText/90608
                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
                Radiologic Imaging

                Cardiovascular Medicine,Nephrology
                Biomarker,Acute renal failure,MRI,Kidney,Imaging,Sepsis
                Cardiovascular Medicine, Nephrology
                Biomarker, Acute renal failure, MRI, Kidney, Imaging, Sepsis


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