#2280 Kidney elastometry, X-flow algorithms to interrogate adult and pediatric number of nephrons
Authors: Viggiano Davide , Iulianiello Pietro , Facchiano Clorinda , Corte Michele Della , Borriello Gianmarco , Gravina Ilenia , Malgieri Gabriele , Petruzzelli Luigi Annicchiarico 
Published: May 2024

Abstract

Background and Aims
Standard ultrasound mainly provides information about structural changes in the kidney, whereas parenchymal Doppler ultrasound provides the renal resistance index (RI), which correlates with plasma creatinine levels. Unfortunately, in the case of isolated proteinuria and normal renal function/creatinine levels, these two classical approaches do not show any changes. Recent advances in ultrasound analysis, allowing the measure of kidney stiffness (sharewave elastometry) and the imaging of ultralow-flow vessels up glomeruli (such as X-Flow), might be helpful to identify kidney alterations in case of proteinuria with normal creatinine.
We hypothesize that proteinuria with intact glomerular filtration may induce a measurable change in kidney stiffness and the size of low-flow microcircle, with different effects in acute and chronic conditions. We also verify whether the mismatch between creatinine, resistance index, and kidney size may suggest a specific nephrological disease.

Method
We conducted a transversal study on 301 patients with chronic kidney disease (CKD) and 160 kidney transplant patients (Tx), comparable for age, gender, and eGFR. For all patients, we retrieved the resistance indices of both the kidney and the spleen, clinical variables, shear wave elastrometry, and the X-Flow algorithm (Esaote) to detect the microcircle. We compared Conventional pulsed wave Doppler techniques (resistance index, RI) and ultrasensitive Doppler algorithm (Xflow, Esaote, Genoa, GE, Italy) to study the perfusion pattern and smaller angio-architecture of kidney's cortical vessels. X-Flow is a high-resolution and high-definition Doppler technology, which, with a new algorithm, makes better spatial resolution possible and maximizes Doppler signal penetration capabilities. We also identify a mismatch between creatinine and the renal RI, calculating the renal mismatch index (correlation between renal resistance index and creatinine level). The connection between the resistance index and the kidney size was tested as a significant marker of chronicity.

Results
The eGFR was best predicted by renal RI in Tx patients (Pearson −0.4, p &lt; 0.01). At variance, the RI is a poor predictor of eGFR in CKD patients: in these subjects, the kidney longitudinal size was a better predictor of eGFR (Pearson's coefficient 0.39, p &lt; 0.01). Using a large dataset from a previous study, we estimated the total number of nephrons using the following approximation: nephron number = (5270*total cortical volume – 61612)*number of kidneys. This formula is only valid for chronic patients and cannot be applied to polycystic patients. We speculated that while eGFR was proportional to the number of active glomeruli in CKD patients (thus correlating with kidney size), in TX patients, the local microcircle better explained the changes in eGFR. The consequence is that the eGFR has different meaning in CKD and Tx patients.
Patients deviating from this pattern are identified as having an increased renal dissimilarity index. The multiple regression analysis revealed that RI also depended on age and cholesterol levels. The spleen resistance index correlated with cholesterol levels. The kidney mismatch index defined a subgroup of patients with tubular microcirculation abnormalities. Shearwave stiffness correlated with Resistance index (Pearson −0.3, p = 0.04) and, limited to Tx patients, to the cortical volume (Pearson = −0.446, p &lt; 0.05) and number of nephrons (Pearson −0.44, p &lt; 0.05), but was not associated with creatinine or eGFR. The extent of microcircle measured on X-flow images was altered in chronic forms of proteinuria with normal creatinine levels.

Conclusion
Kidney elastometry and kidney X-flow indices might show more sources of profitable information that can be collected from ultrasound approaches that allow the identification of a diseased kidney, even in the presence of regular architecture and average resistance index. The X-flow algorithm should be used to study the smaller vascular tree not visualizable with Doppler, such as the afferent arteriole.