Compact Point of Care Ultrasound Reveals Hemodynamic Abnormalities in Children with Sickle Cell Disease

In sickle cell disease (SCD), kidney related morbidity and mortality are significant, with ~80% of patients displaying signs of chronic kidney disease (CKD) by age 40¹ and kidney related mortality being the third leading cause of death (16.4%)². Children with SCD are also prone to kidney disease with 20% of 12 years-old displaying microalbuminuria⁴ and enuresis and hyposthenuria commonly observed in infants⁴.

Current clinical guidelines are insufficient as they ignore pediatric disease until the development of late signs like proteinuria or large drops in eGFR have occurred⁵. A major limitation in the assessment of kidney disease in children with SCD is the incomplete understanding of disease progression and the lack of suitable biomarkers to discriminate health and disease. Serum creatinine based eGFR is the most common biomarker of kidney function but is poorly validated and relatively insensitive in SCD patients due low muscle mass and hyperfiltration⁶.

Point of care ultrasound (POCUS) offers a non-invasive alternative to blood based biomarkers. POCUS has proven clinical utility in decreasing primary and secondary stroke⁷. Additionally, POCUS technology now offers compact, cartless systems, with tablet and smartphone compatibility, multiprobe functionality in a single probe and an economical price point (<3000$)⁸.

Therefore, the goals of this study were two-fold. 1) Determine the feasibility of renal assessment using compact POCUS in children with SCD in a clinical setting. 2) Establish normative values for possible compact POCUS biomarkers that could supplement existing biomarkers of kidney disease in SCD.

Methods: Studies were performed with informed consent under an IRB approved protocol. 18 patients with SCD were recruited during their routine clinical visit to undergo a 10-20 minute ultrasound examination. All POCUS exams were performed in supine position, on the right kidney by an experienced imaging researcher (AB, +10 years).

Images were acquired with a Butterfly IQ+ (Burlington, MA, USA) system and an Apple Smartphone (Cupertino, CA, USA). The abdominal preset and B-mode imaging was used to determine the long axis renal length and echogenicity of the renal/liver parenchyma. The cardiac preset, pulsed Doppler mode was used to determine the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI = (PSV-EDV)/PSV) of the main right renal artery.

Images were saved to a cloud based, HIPPA protected database, downloaded to a local workstation and processed using custom MATLAB scripts. An angle correction of 1/cos(60°) was applied to the uncorrected velocity values.

Results: Renal length and serum creatinine was measured in 18 patients with SCD (3 HbSC, 15 HbSS) and pulsed Doppler estimates were obtained in 14 of 18 subjects (hemoglobin 9.9±2.3,12 male). The average renal length was 8.7±1.3 cms and serum creatinine was 0.69±0.16 and showed a statistically significant increase with respect to age (Figure 1). The average angle corrected main renal artery PSV was 74.5±64.4 cm/s and RI was 0.49±0.33 and both decreased with respect to age (Figure 1). The average echogenicity ratio between kidney and liver parenchyma was 0.64±0.14 and was uncorrelated with age.

Discussion: This work demonstrates that high quality structural and hemodynamic images can be acquired with low cost, compact POCUS in a clinical setting. The age dependent increase in serum creatinine⁹ and kidney length¹⁰ were in good agreement with prior cart-based sonography work in healthy children. Conversely, the age dependent drop in main renal artery PSV and RI was in opposition to work in healthy children that showed no change¹¹ or an increase with age¹².

The clinical significance of abnormally elevated velocity in young children with SCD and its impact on the development of sickle nephropathy should be studied in more detail. Future work comparing cross-sectional and longitudinal variability in compact POCUS and physiologic biomarkers of kidney function in both pediatric and adult subjects with and without SCD is ongoing.

References: 1) Guasch et al. 2006 2) Powars et al. 2005 3) Aygun et al. 2011 4) Mcpherson et al. 2011 5)Liem et al. 2019 6) Asnani et al. 2013 7) Adams et al. 2005 8) Lee et al. 2020 9) Liu et al 2019 10) Rosenbaum et al. 1984 11) Grunert et al. 1990 12) Deeg et al. 2003 13) Cutajar et al. 2010

No relevant conflicts of interest to declare.