Hyperpolarized [1‐13C] alanine production: A novel imaging biomarker of renal fibrosis

Purpose Renal tubulointerstitial fibrosis is strongly linked to the progressive decline of renal function seen in chronic kidney disease. State‐of‐the‐art noninvasive diagnostic modalities are currently unable to detect the earliest changes associated with the onset of fibrosis. This study was undertaken to evaluate the potential for detecting the earliest alterations in fibrogenesis using a biofluid‐based method and metabolic hyperpolarized [1‐13C]pyruvate imaging. Methods We evaluated renal fibrosis in a combined ischemia reperfusion–induced and streptozotocin‐induced diabetic nephropathy rodent model by hyperpolarized [1‐13C]pyruvate MRI and correlated the metabolic MRI parameters with biomarkers of fibrosis measured on renal tissue and plasma/urine. Results The hyperglycemic rats experienced maladaptive injury repair after the ischemic insults, as shown by the elevation in the injury markers kidney injury molecule‐1 and neutrophil gelatinase–associated lipocalin. Renal function was significantly impaired in the ischemic hyperglycemic kidney, as seen in the reduced perfusion and single‐kidney glomerular filtration rate. A deranged energy metabolism was detected in the ischemic hyperglycemic kidney, as seen in the reduced fractional perfusion of lactate. Renal fibrosis biomarkers correlated significantly with the alanine production. Conclusion Hyperpolarized carbon‐13 MRI provides a promising approach to assess renal fibrosis in an animal model of fibrotic chronic kidney disease. In particular, the metabolic supply of amino acids for fibrogenesis (alanine production) correlates well with biomarkers of fibrosis. Thus, [1‐13C]pyruvate‐to‐[1‐13C]alanine conversion might be a candidate for noninvasive assessment of renal fibrogenesis.