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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 [1]. 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 and resistance index and kidney size may suggest a specific nephrological disease. Finally, we test wether the use of Empagliflozin gives a signal using these new ultrasound methods.
We conducted a transversal study on 468 patients comprising a group with proteinuria and normal creatinine levels, a control group with proteinuria and high creatinine levels and 20 patients in treatment with Empagliflozin for proteinuria without heart disease or diabetes.
We retrieved for all patients the resistance indices of both the kidney and the spleen, clinical variables, shear wave elastrometry, and X-Flow algorithm (Esaote) to detect the microcircle. We compared Conventional pulsed wave Doppler techniques (resistance index, RI) and ultrasensitive usDoppler algorithm (Xflow, Esaote, Genoa, GE, Italy) to study the perfusion pattern and smaller angio-architecture of kidney’s cortical vessels. Xflow is a high-resolution and high-definition Doppler technology, which, with a new algorithm, makes possible better spatial resolution 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.
Renal RI significantly correlates with creatinine values (Pearson 0.318, p <0.01). However, some patients deviate from this pattern (increased renal dissimilarity index). The multiple regression analysis revealed that RI depended on age and cholesterol levels, too. The spleen resistance index did not correlate with creatinine, while it correlated with cholesterol levels. The kidney mismatch index defined a subgroup of patients with tubular microcirculation abnormalities. Shear wave stiffness correlated with the extent of proteinuria (Pearson coeff. 0.497, p=0.008) and was not associated with creatinine. Empagliflozin treatment induced a significant modification of kidney stiffness.
Overall, creatinine levels could be considered and predicted by the size of the kidney (longitudinal diameter, LD) and by the index of renal resistance (RI) using this formula/the following formula: creatinine = 1.8 -0.175*LD + 2.601* RI
The extent of microcircle measured on X-flow images was altered in chronic forms of proteinuria with normal creatinine levels.
Kidney elastometry and kidney X-flow indices might show more sources of profitable information that can be collected from ultrasound approaches that allow to identify a diseased kidney even in presence of regular architecture and normal resistance index. X flow algorithm should be used to study the smaller vascular tree not visualizable with Doppler such as afferent arteriole.