U.S. Department of Health and Human Services

Delving deep into the kidney with a novel imaging technique

Scientists have developed a new imaging technique that allows them to see deep into the kidney’s internal structures and gain novel insights about cisplatin-induced chronic kidney disease (CKD) in mice. Cisplatin is a chemotherapy drug that is used to treat various types of cancer. However, some people taking the drug develop CKD, which limits the drug’s usefulness. To investigate how cisplatin treatment causes kidney damage, researchers first generated a new mouse model of cisplatin-induced CKD by administering two doses of the drug to mice 2 weeks apart. The animals developed CKD similarly to what is seen in people taking the drug. To examine the resulting kidney damage in the mice, the researchers used a specialized imaging technique, called multiphoton microscopy. However, a major limitation to using this technique is that it only gives a shallow view of the organ. To overcome this barrier, the scientists used a novel way to process samples of kidney tissue before looking at them under the microscope—they used a “clearing” solution that replaced the water in the tissue with other chemicals. Use of this clearing solution greatly increased the imaging depth so that the microscope could produce high-resolution three-dimensional images deep inside the kidneys of the mice; this allowed the scientists to observe the damage caused by cisplatin. For example, they found that cisplatin treatment reduced the number of a type of cell (cuboidal cells) in the capsule of the glomerulus—the fundamental filtering apparatus in the kidney.  The loss of cuboidal cells corresponded, almost exactly, to reduced kidney function. The observations made in this study, as well as future research using this new approach, could provide novel insights about kidney damage caused by cisplatin and identify prevention targets to make the drug safer for people. Additionally, the imaging technique could be used to study other forms of kidney damage, such as kidney disease caused by diabetes or high blood pressure.

Torres R, Velazquez H, Chang JJ,…Safirstein R. Three-dimensional morphology by multiphoton microscopy with clearing in a model of cisplatin-induced CKD. J Am Soc Nephrol 27:1102-1112, 2016.