Urinary Angiotensinogen Predicts Persistent Albuminuria in Sickle Cell Anemia

The biomarker urinary angiotensinogen (AGT) is predictive of persistent albuminuria (PA) in adult patients with sickle cell anemia (SCA), according to a study in the British Journal of Haematology that evaluated the association of biomarkers with PA.¹

“What we’re most excited about is that urinary angiotensinogen was not only highly sensitive for PA in patients with sickle cell anemia, but was independently associated with PA. What will be even more exciting is if we’re able to find that urinary angiotensinogen can predict patients who will develop PA,” senior author Kenneth I. Ataga told The American Journal of Managed Care^®.

Sickle cell anemia affects an estimated 100,000 people in the US | image credit: Studios - stock.adobe.com

In a prospective, longitudinal cohort study of 280 patients in North Carolina, Tennessee and Ohio, slightly more than a third of patients with SCA exhibited PA. Researchers evaluated the association of biomarkers of endothelial function, coagulation activation, glomerular and kidney tubular injury with PA.

Patients with PA were found to have significantly higher levels of median plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) (1176.3 vs. 953.4 ng/mL), thrombin–antithrombin complex (5.5 vs. 4.7 ng/mL), and urinary angiotensinogen (12.2 vs. 5.3 ng/mg), urinary nephrin (30.6 vs. 27.2 ng/mg), and urinary kidney injury molecule-1 (KIM-1) (0.8 vs. 0.5 ng/mg), normalized to urine creatinine.

In multivariable analysis, urinary AGT was the only significant predictor of PA. Soluble VCAM-1, D-dimer, urinary AGT, KIM-1, and nephrin were significantly associated with urine albumin–creatinine ratio.

PA was defined as urine albumin–creatinine ratio (ACR) values of 30 mg/g of creatinine or higher, obtained in at least 2 out of 3 spot urine collections within 6 months of the research visit or a single urine ACR value of 100 mg/g or higher, obtained at the research visit if only one assessment was available.

Patients were excluded who had a history of diabetes mellitus with suspicion of diabetic nephropathy as determined by a nephrologist, had known hepatitis B or C infection or HIV infection, history of cancer except for non-melanoma skin cancer, connective tissue disease such as systemic lupus erythematous, known glomerular disease unrelated to SCA, end-stage kidney disease on chronic dialysis, were pregnant, breastfeeding, or had undergone bone marrow or kidney transplantation.

SCA affects an estimated 100,000 Americans, and millions of people worldwide, according to the study. Albuminuria is an early clinical symptom of CKD. Multiple studies have found an association of CKD, regardless of severity, with increased mortality in adult patients with SCA.

“[I]dentification of biomarkers that predict the development and progression of CKD in SCA presents an opportunity to prevent its onset, slow its progression and ultimately reduce mortality,” the authors wrote.

Sickled cells can result in reduced blood flow to the kidneys, which may cause kidney damage and chronic kidney disease, according to the CDC.² The kidneys filter waste from blood and produce urine. When the kidney lacks oxygen, kidney cells can die. As a result, the kidney cannot filter out waste adequately and excessive urination can result.

“[A]n increase in urinary AGT has been reported to precede the onset of albuminuria in normotensive adults with diabetes, suggesting that urinary AGT may also predict early kidneydamage in SCA. However, longitudinal studies are required to evaluate the utility of urinary AGT in predicting incident albuminuria and decline of kidney function in SCA. Further investigation is also warranted as to whether intervention in those with urinary AGT elevation can delay the onset of CKD,” the authors wrote.¹

References

1. Elsherif L, Tang Y, Patillo K, et al. Association of biomarkers of endothelial function, coagulation activation and kidney injury with persistent albuminuria in sickle cell anaemia. BR J Haematol. Published online September 3, 2024. doi:10.1111/bjh.19743
2. Sickle Cell Disease. CDC.gov. Accessed Sept. 18, 2024. https://www.cdc.gov/sickle-cell/complications/kidney-problems.html