Blood test may improve kidney damage detection in children with SCD
Measuring levels of cystatin C protein could prove to be more reliable method
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A blood test measuring levels of the protein cystatin C may provide a more reliable way to monitor for kidney problems in children and young adults with sickle cell disease (SCD), a small study suggests.
Data showed that commonly used formulas based on creatinine-to-protein ratio, a well-established kidney damage marker, tended to overestimate kidney function more than cystatin C-based formulas, potentially masking early signs of kidney damage.
“This pilot study demonstrates the feasibility and potential relevance of cystatin C–based [kidney function] estimation in children with SCD,” researchers wrote.
The study, “Kidney function monitoring in pediatric sickle cell disease: evidence from the NEPHRODREPA study,” was published in Pediatric Nephrology by a team led by researchers in France.
Kidney complications among most severe SCD manifestations
The production of a faulty version of hemoglobin, the oxygen-carrying protein in red blood cells, causes SCD. As a result, red blood cells acquire a sickle-like shape, making them more prone to destruction and to forming clumps that block blood flow in small vessels, thereby reducing oxygen delivery to tissues.
“Kidney complications are among the most severe and frequent manifestations of SCD,” the researchers wrote.
These complications start in childhood, with glomerular hyperfiltration — an abnormally high kidney filtration rate that acts as an early compensatory mechanism — and hyposthenuria, or the inability of the kidneys to concentrate urine, resulting in excessively diluted urine. Over time, up to 15% of SCD patients develop chronic kidney disease.
However, “kidney function assessment in SCD remains challenging, as traditional biomarkers like [blood] creatinine and Schwartz-based estimated glomerular filtration rate (eGFR) often overestimate kidney function,” the researchers wrote.
Schwartz-based eGFR is a test that measures how well the kidneys filter waste in pediatric patients, usually based on age, sex, and blood levels of creatinine.
In children with SCD, creatinine-based eGFR formulas usually overestimate filtration rates relative to reference isotopic measures, which assess kidney filtration rate by tracking how quickly a substance labeled with a radioactive tracer is cleared from the blood.
However, this gold standard method is “impractical for annual monitoring in SCD due to high cost, lengthy procedure, radiation exposure, and the difficulty of obtaining multiple blood samples from anemic children,” the researchers wrote.
Therefore, identifying better kidney function markers may help to improve the monitoring of kidney damage in children with SCD.
Cystatin C is ‘a promising biomarker’
Cystatin C is “a promising biomarker for assessing GFR, as it provides a reliable estimate of GFR,” the researchers wrote, adding that unlike creatinine, it is not affected by “muscle mass, …, hemoglobin, or [kidney tube] hyperactivity, factors commonly altered in SCD.”
In this pilot study, called NEPHRODREPA, researchers compared the performance of eGFR formulas based on creatinine and/or cystatin C with the gold-standard isotopic GFR measurements in children and young adults with SCD without known kidney damage.
Creatinine and cystatin C formulas were based on the Chronic Kidney Disease in Children Under 25 (CKiDU25) equation, which accounts for age- and sex-dependent constants, height, and blood creatinine. It is used in people up to age 25.
A total of 13 children and four adults, with median ages of 11.4 and 20.7 years, respectively, were enrolled at a single center in France. Most participants were male (58.8%) and had a history of vaso-occlusive crises (82.4%) — when sickled red blood cells block blood flow, depriving tissues of oxygen and causing pain.
Blood tests showed that patients’ median levels of creatinine and cystatin C were within the normal range, as were values of isotopic GFR measurements for all patients, indicating normal kidney function.
This study suggests that in young patients with SCD without known [kidney disease], the CKiDU25 equation using [blood] cystatin C, provides GFR estimates close to the gold standard isotopic measurement.
CKiDU25 formulas based on creatinine or both creatinine and cystatin C levels overestimated GFR by 17% and 10%, respectively, with results being significantly different from those obtained using the isotropic method.
In contrast, the CKiDU25 formula incorporating cystatin C levels alone underestimated GFR by only 5%, with no significant difference from GFR values obtained using the isotropic method.
“Cystatin C-based estimation provided values more closely aligned with isotopic measurements,” the researchers wrote.
As for additional kidney function measurements, 41.2% of patients had hyposthenuria, and 47.1% had elevated blood levels of the hormone renin, which is released by the kidneys in response to low blood pressure or low sodium levels. These conditions are indicative of early tubular disorders, when kidney tubules, which normally filter waste and reabsorb water and salts, fail to function properly.
Imaging tests, performed in 11 participants, did not reveal any kidney abnormalities.
Overall, “this study suggests that in young patients with SCD without known [kidney disease], the CKiDU25 equation using [blood] cystatin C provides GFR estimates close to the gold standard isotopic measurement,” the researchers wrote. “Confirmation of these preliminary results in larger [follow-up studies] is warranted to refine follow-up strategies in patients without advanced [SCD-related kidney damage] and to incorporate early monitoring of tubular dysfunction markers for timely therapeutic intervention.”
