## 4 Discussion  
In healthy and diseased left and right kidneys from two genders and two species, we report that calculation of renal dimensions using a modified ellipse-based formula provides a better estimate of both measured renal parenchymal area and measured TKV in comparison to the existing ellipse-based formula. Accurate determination of renal dimension is critical to a number of subspecialties within nephrology. Accurate measurement of renal metrics is also critical to inform changes in values from previous measurements. In the CKD patient, functional changes are long preceded by extracellular matrix accumulation within the renal interstitium and parenchymal echogenicity, and abnormalities in renal size often inform presence of some disease [1; 2; 3]. Autosomal dominant and autosomal recessive PKD is characterized by increased TKV with both TKV, and its rate of increase, a prognostic biomarker for outcome in these populations [4; 5; 6]. Consequently, there is increasing interest within the nephrology community and pharmaceutical companies to use TKV as a surrogate endpoint in PKD trials to define the efficacy of drug candidates [7]. In renal transplantation, organ size is critical to match a donor with the recipient, and is especially the case with pediatric recipients. Kidney size can also inform allograft rejection as it has been reported that transplants with severe rejection had either an abnormal renal length or renal growth rate or both [8; 9; 10]. Changes in kidney size can also inform vesicoureteral reflux, infections within that organ, renal insufficiency and threats to the prospective mother in the setting of pregnancy [20]. Finally, determination of TKV is important in the debulking of renal tumors as it can dictate margins [21]. Remnant nephron mass governs renal function, especially in kidneys with prior functional impairment. Given the impracticality of using the gold-standard fluid displacement method, imaging has become the mainstay for reporting kidney volume and changes in kidney volume. Ultrasonography is readily available, cost-effective, non-toxic therefore affording repeated measurements, and requires minimal patient compliance unlike more expensive imaging modalities which might also involve use of a contrast agent that might be nephrotoxic. Kidney volume is calculated using an ellipse-based formula  
Figure 9: Measured vs. calculated total kidney volume (TKV). (**A**) An H&E-stained coronal renal slice from a PCK rat. The major axis (_a_), minor axis (_b_), and extended minor axis are shown (_be_). (**B**) Kidney volume calculated using the existing formula was lower than measured TKV whereas kidney volume calculated using the modified formula was not different from the measured TKV (\({}^{*}\), \(p<0.01\) vs). following measurement of renal length, width and thickness [11; 12; 13; 15]. Nevertheless, data from a number of studies [11; 12; 13; 15] have consistently shown that use of this method underestimates kidney size by \(\sim\)25%. In fact, the existing method underestimates renal size regardless of whether the kidney is healthy or diseased and regardless of whether the image is obtained by ultrasound or magnetic resonance [13; 15]. In a seminal study [13] by [PERSON] and colleagues, porcine kidney volumes measured by the magnetic resonance imaging disc-summation method was within 5% of the actual kidney volume measured by the fluid displacement method. In contrast, applying the existing ellipse-based formula to the magnetic resonance images underestimated TKV by 17% to 29%. A comprehensive clinical study [15] to determine the accuracy and repeatability of ultrasonography and the existing formula to calculate TKV concluded that this formula is neither appropriate for accuracy nor reproducible for such a determination. Recently, this laboratory [16] reported a modification to this methodology using a murine model of kidney disease.