Abstract
Histological evaluation of renal biopsies is currently the gold standard for acquiring important diagnostic and prognostic information in diabetic nephropathy (DN) patients. Nevertheless, there is an unmet clinical need for new biomarkers that allow earlier diagnosis and risk stratification. As biochemical changes in tissues must precede any symptomatic or morphological expression of a disease, we explored the potential of near-infrared (NIR) spectroscopy in the detection of a biochemical signature associated with DN. Kidney tissue sections were investigated using NIR spectroscopy, followed by principal component analysis and soft independent modelling of class analogy. A biochemical signature indicative of DN was detected, which enabled perfect discrimination between tissue sections with normal histological findings (n = 27) and sections obtained from DN patients (n = 26). Some spectral changes related to carbamoylation and glycation reactions appeared to be similar to the ones obtained in patients with DN. In addition, treatment with the deglycating enzyme fructosamine-3-kinase resulted in partial to pronounced restorations of the spectral pattern. Significant relationships were found between spectral features and laboratory parameters indicative of glycemic and uremic load, such as hemoglobin A1c, urea, creatinine, estimated glomerular filtration rate, and proteinuria. The presented method could be a useful tool to complement histopathological analysis in order to prevent or delay further disease progression, especially in the setting of post-transplant surveillance kidney biopsies.
Highlights
Around 20%–40% of patients with type 1 or type 2 diabetes mellitus (DM) develop diabetic nephropathy (DN) [1]
We explored for the first time the potential of NIR spectroscopy to identify and unravel a biochemical signature associated with DN on stained tissue sections
We have demonstrated for the first time the use of NIR spectroscopy to assess DN in renal biopsies from a single stained tissue section
Summary
Around 20%–40% of patients with type 1 or type 2 diabetes mellitus (DM) develop diabetic nephropathy (DN) [1] The latter is a clinical syndrome characterized by persistent albuminuria (>300 mg/24 h or > 300 mg/g creatinine), a decline in glomerular filtration rate (GFR), elevated blood pressure, and an excess cardiovascular morbidity and mortality [1,2]. Detection of DN using vibrational spectroscopy was first reported by Varma et al [4], who employed spectroscopic imaging in the mid-infrared (MIR) range to identify early biochemical changes associated with recurrence of disease in transplant patients prior to histologic changes. We explored for the first time the potential of NIR spectroscopy to identify and unravel a biochemical signature associated with DN on stained tissue sections
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