A collagen-binding protein enables molecular imaging of kidney fibrosis in vivo

Pathological deposition of collagen is a hallmark of kidney fibrosis. To illustrate this process we employed multimodal optical imaging to visualize and quantify collagen deposition in murine models of kidney fibrosis (ischemia-reperfusion or unilateral ureteral obstruction) using the collagen-binding adhesion protein CNA35. For in vivo imaging, we used hybrid computed tomography-fluorescence molecular tomography and CNA35 labeled with the near-infrared fluorophore Cy7. Upon intravenous injection, CNA35-Cy7 accumulation was significantly higher in fibrotic compared to non-fibrotic kidneys. This difference was not detected for a non-specific scrambled version of CNA35-Cy7. Ex vivo, on kidney sections of mice and patients with renal fibrosis, CNA35-FITC co-localized with fibrotic collagen type I and III, but not with the basement membrane collagen type IV. Following intravenous injection, CNA35-FITC bound to both interstitial and perivascular fibrotic areas. In line with this perivascular accumulation, we observed significant perivascular fibrosis in the mouse models and in biopsy sections from patients with chronic kidney disease using computer-based morphometry quantification. Thus, molecular imaging of collagen using CNA35 enabled specific non-invasive quantification of kidney fibrosis. Collagen imaging revealed significant perivascular fibrosis as a consistent component next to the more commonly assessed interstitial fibrosis. Our results lay the basis for further probe and protocol optimization towards the clinical translation of molecular imaging of kidney fibrosis. Pathological deposition of collagen is a hallmark of kidney fibrosis. To illustrate this process we employed multimodal optical imaging to visualize and quantify collagen deposition in murine models of kidney fibrosis (ischemia-reperfusion or unilateral ureteral obstruction) using the collagen-binding adhesion protein CNA35. For in vivo imaging, we used hybrid computed tomography-fluorescence molecular tomography and CNA35 labeled with the near-infrared fluorophore Cy7. Upon intravenous injection, CNA35-Cy7 accumulation was significantly higher in fibrotic compared to non-fibrotic kidneys. This difference was not detected for a non-specific scrambled version of CNA35-Cy7. Ex vivo, on kidney sections of mice and patients with renal fibrosis, CNA35-FITC co-localized with fibrotic collagen type I and III, but not with the basement membrane collagen type IV. Following intravenous injection, CNA35-FITC bound to both interstitial and perivascular fibrotic areas. In line with this perivascular accumulation, we observed significant perivascular fibrosis in the mouse models and in biopsy sections from patients with chronic kidney disease using computer-based morphometry quantification. Thus, molecular imaging of collagen using CNA35 enabled specific non-invasive quantification of kidney fibrosis. Collagen imaging revealed significant perivascular fibrosis as a consistent component next to the more commonly assessed interstitial fibrosis. Our results lay the basis for further probe and protocol optimization towards the clinical translation of molecular imaging of kidney fibrosis. In this issueKidney InternationalVol. 97Issue 3PreviewProgressive kidney diseases result in interstitial fibrosis, and successful therapies must abrogate this accumulation of scar. However, because clinical markers of progression change slowly, and frequently repeated histologic investigation is not practical, success has been difficult to assess in clinical trials and practice. Baues et al. addressed this, describing the results of optical imaging for collagen types I and III (scar collagen) using a fluorescently tagged molecular probe (collagen-binding adhesion protein CNA35). Full-Text PDF The scar that never felt a woundKidney InternationalVol. 97Issue 3PreviewChronic kidney disease is inevitably associated with the proliferation of fibroblasts following injury of the tubular system and collagen deposition in the interstitial tissue. To date, renal fibrosis has been hard to detect without histologic tissue examination. In this issue of Kidney International, Baues et al. introduce a novel technology for noninvasive detection of renal fibrosis using a multimodal optical approach with the fluorescent-labelled collagen-binding agent CNA35-Cy7. Full-Text PDF Visualizing fibrosis—hope for ideal markers beyond imagingKidney InternationalVol. 97Issue 3PreviewHow do nephrologists, or physicians, evaluate chronic kidney disease (CKD) progression? Clinically, the progression of CKD is routinely assessed by the decrease in estimated glomerular filtration rate and histologically by expansion of the fibrotic area. Unfortunately, the level of estimated glomerular filtration rate does not always precisely reflect the extent of kidney fibrosis. The gap between the estimated glomerular filtration rate (the clinical indicator of the renal function of toxin excretion) and the interstitial fibrosis and tubular atrophy index (the histological index of collagen accumulation) complicates the precise understanding and evaluation of CKD progression. Full-Text PDF