A modified elliptical formula to estimate kidney collagen content in a model of chronic kidney disease.

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.

An Empirical Biomarker-Based Calculator for Cystic Index in a Model of Autosomal Recessive Polycystic Kidney Disease-The Nieto-Narayan Formula.

Autosomal recessive polycystic kidney disease (ARPKD) is associated with progressive enlargement of the kidneys fuelled by the formation and expansion of fluid-filled cysts. The disease is congenital and children that do not succumb to it during the neonatal period will, by age 10 years, more often than not, require nephrectomy+renal replacement therapy for management of both pain and renal insufficiency. Since increasing cystic index (CI; percent of kidney occupied by cysts) drives both renal expansion and organ dysfunction, management of these patients, including decisions such as elective nephrectomy and prioritization on the transplant waitlist, could clearly benefit from serial determination of CI. So also, clinical trials in ARPKD evaluating the efficacy of novel drug candidates could benefit from serial determination of CI. Although ultrasound is currently the imaging modality of choice for diagnosis of ARPKD, its utilization for assessing disease progression is highly limited. Magnetic resonance imaging or computed tomography, although more reliable for determination of CI, are expensive, time-consuming and somewhat impractical in the pediatric population. Using a well-established mammalian model of ARPKD, we undertook a big data-like analysis of minimally- or non-invasive blood and urine biomarkers of renal injury/dysfunction to derive a family of equations for estimating CI. We then applied a signal averaging protocol to distill these equations to a single empirical formula for calculation of CI. Such a formula will eventually find use in identifying and monitoring patients at high risk for progressing to end-stage renal disease and aid in the conduct of clinical trials.