A Method for the Evaluation of Site-Specific Nephrotoxic Injury in the Intact Rat Kidney.

In a previously published report we detailed an in situ method to quantify cell death in the renal cortex by perfusing the cell membrane impermeable fluorochrome, ethidium homodimer in situ. The objective of the present study was to use this in situ viability assay to examine cell death following the administration of nephrotoxic drugs known to produce cell death and/or injury in specific segments of the nephron. Male Sprague/Dawley rats were treated with the following nephrotoxicants: Gentamicin, amphotericin-B, and indomethacin. Results of the in situ viability assay indicated that gentamicin and amphotericin-B treatment caused cell death localized in the kidney cortex and medulla, respectively. The urinary biomarker kidney injury molecule-1 (Kim-1) showed significant increases in both gentamicin (20 fold increase) and amphotericin-B-treated (9.2 fold increase) animals. Urinary alpha glutathione-S-transferase (GST) showed significant increases for gentamicin (6.2 fold increase) only and mu GST for amphotericin-B-treated (19.1 fold increase) animals only. These results show that this in situ viability assay provides a sensitive method to identify cell death in different regions of the kidney. Furthermore, urinary alpha GST and mu GST are specific for proximal and distal tubule injury, respectively; urinary Kim-1 demonstrated greater sensitivity to both proximal and distal tubule injury.

Fusion FDG-PET/MRI Evidence to Support Diagnosis of Frontotemporal Dementia-Related Primary Progressive Aphasia.

A 61-year-old right-handed man presented for cognitive neurological evaluation with word-finding difficulty, impaired word retrieval, impaired repetition of phrases, and stammering. Brain MRI and FDG-PET/CT were performed as initial imaging workup. Further FDG PET/MRI brain images were obtained through software fusion and revealed regional cortical atrophy with corresponding hypometabolic activity involving the posterior aspects of the left middle and inferior temporal gyri. These characteristic imaging findings are supportive of patient's diagnosis of frontotemporal dementia-related primary progressive aphasia.

Evaluation of cystatin C as an early biomarker of cadmium nephrotoxicity in the rat.

Cadmium (Cd) is a nephrotoxic environmental pollutant that causes insidious injury to the proximal tubule that results in severe polyuria and proteinuria. Cystatin C is a low molecular weight protein that is being evaluated as a serum and urinary biomarker for various types of ischemic and nephrotoxic renal injury. The objective of the present study was to determine if cystatin C might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. At 3, 6, 9 and 12 weeks, urine samples were analyzed for cystatin C, protein, creatinine, ß2 microglobulin and kidney injury molecule-1. The results showed that Cd caused a significant increase in the urinary excretion of cystatin C that occurred 3-4 weeks before the onset of polyuria and proteinuria. Serum levels of cystatin C were not altered by Cd. Immunolabeling studies showed that Cd caused the relocalization of cystatin C from the cytoplasm to the apical surface of the epithelial cells of the proximal tubule. The Cd-induced changes in cystatin C labelling paralleled those of the brush border transport protein, megalin, which has been implicated as a mediator of cystatin C uptake in the proximal tubule. These results indicate that Cd increases the urinary excretion of cystatin C, and they suggest that this effect may involve disruption of megalin-mediated uptake of cystatin C by epithelial cells of the proximal tubule.

FDG PET/CT Manifestation of Rare Widespread Metastatic Chemoradiation-Refractory Thymic Squamous Cell Carcinoma.

A 74-year-old man underwent excisional biopsy of an anterior mediastinal mass that revealed squamous cell carcinoma of thymic origin. Immunohistochemistry revealed insulin-like growth factor-1 receptor positivity, which has been associated with worse prognosis. Restaging FDG PET/CT revealed extensive soft tissue and osseous metastases despite surgery and chemoradiation therapy. Patient was then enrolled in a clinical trial with anti-insulin-like growth factor-1 receptor therapy. A 3-month follow-up FDG PET/CT showed disease progression with an increase in size and number of hypermetabolic metastatic lesions, including interval development of multiple new metastases.