Abstract
The extent of scarring or renal interstitial collagen deposition in chronic kidney disease (CKD) can only be ascertained by highly invasive, painful and sometimes risky, tissue biopsy. Interestingly, while CKD-related abnormalities in kidney size can often be visualized using ultrasound, not only does the ellipsoid formula used today underestimate true renal size, but the calculated renal size does not inform tubulointerstitial collagen content. We used coronal kidney sections from healthy mice and mice with kidney disease to develop a new formula for estimating renal parenchymal area. While treating the kidney as an ellipse with the major axis (a) the polar distance, this technique involves extending the minor axis (b) into the renal pelvis to obtain a new minor axis, be. The calculated renal parenchymal area is remarkably similar to the true or measured area. Biochemically determined kidney collagen content revealed a strong and positive correlation with the calculated renal parenchymal area. Picrosirius red staining for tubulointerstitial collagen also correlated with calculated renal parenchymal area. The extent of renal scarring, i.e. kidney interstitial collagen content, can now be computed by making just two axial measurements which can easily be accomplished via noninvasive imaging of this organ.
Highlights
Given the prevalence of diabetes, hypertension and Metabolic Syndrome, chronic kidney disease (CKD) is reaching epidemic proportions across the world [1,2]
In a model of murine uniphrectomy+DOCA+NaCl-induced CKD,_wee report that a) renal fibrosis is evidenced by increased total kidney collagen content or increased tubulointerstitial collagen, b) kidney collagen is directly proportional to renal parenchymal area and c) a new technique involving just two linear axial measurements allows for calculation of renal parenchymal area
Management of the CKD patient continues to present a challenge for the nephrologist given that functional changes are long preceded by extracellular matrix accumulation within the renal interstitium, and given that highly invasive and painful tissue biopsy remains the mainstay for determining the extent of scarring [5]
Summary
Given the prevalence of diabetes, hypertension and Metabolic Syndrome, chronic kidney disease (CKD) is reaching epidemic proportions across the world [1,2]. Characterized by scarring or accumulation of fibrillar collagen within the renal interstitium, CKD is associated with a progressive decline in renal function. Existing disease is often diagnosed late because clinically meaningful changes in renal function occur long after substantial and irreversible scar formation [3,4]. Further compounding both disease diagnosis and prognosis is the fact that highly invasive renal biopsy remains the mainstay for determining the extent of renal scarring [5].
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