Urinary Biomarkers for the Assessment of Acute Kidney Injury of Pediatric Sickle Cell Anemia Patients Admitted for Severe Vaso-occlusive Crises

Abstract

Sickle cell nephropathy is a progressive morbidity, beginning in childhood, which is incompletely understood partially due to insensitive measures. We performed a prospective pilot study of pediatric and young adult patients with sickle cell anemia (SCA) to assess urinary biomarkers during acute pain crises. Four biomarkers were analyzed with elevations potentially suggesting acute kidney injury: (1) neutrophil gelatinase-associated lipocalin (NGAL), (2) kidney injury molecule-1, (3) albumin, and (4) nephrin. Fourteen unique patients were admitted for severe pain crises and were found to be representative of a larger SCA population. Urine samples were collected at the time of admission, during admission, and at follow-up after discharge. Exploratory analyses compared cohort values to the best available population values; individuals were also compared against themselves at various time points. Albumin was found to be moderately elevated for an individual during admission compared with follow-up (P = 0.006, Hedge g: 0.67). Albumin was not found to be elevated compared with population values. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and nephrin were not found to be significantly elevated compared with population values or comparing admission to follow-up. Though albumin was found to be minimally elevated, further research should focus on alternative markers in efforts to further understand kidney disease in patients with SCA.

Nontargeted Plasma Proteomic Analysis of Renal Disease and Pulmonary Hypertension in Patients with Sickle Cell Disease

“…The identification of biomarkers associated with clinical measures of SCDN and pHTN in blood, an easily accessible tissue, offers great promise for earlier diagnosis. One example is cystatin-C, a cysteine proteinase inhibitor, that was first proposed as a biomarker of glomerular filtration in 1985 and has since been widely utilized for chronic kidney disease (CKD) diagnosis, outperforming traditional measures such as creatinine as it is less dependent on muscle mass and biological factors. − Still, CKD diagnosis using cystatin-C is far from perfect, and misclassification errors are common. , In the quest for more accurate predictive and diagnostic parameters, many potential biomarkers for CKD have been studied, including cytokines and chemokines, urinary proteins related to inflammation and tissue repair, as well as efforts to improve GFR estimation using serum metabolites. − It is unclear how these biomarkers for CKD will translate to SCDN, as the mechanisms underlying disease pathogenesis are unique given the chronic hemolysis and anemia that exacerbate kidney injury in SCD. − Moreover, hyperfiltration and hypersecretion into the renal tubules at early stages of SCDN may make creatinine clearance rates misleading. , Several novel SCDN biomarkers have been proposed, ,− however many of these studies suffered from small sample size and/or limitations of targeted analysis. Far fewer studies have investigated a role for biomarkers in early detection of pHTN in SCD patients. − However, protein biomarkers for cardiovascular disease have been associated with kidney function in the general population, and interestingly, sFLT-1 has been associated with both SCDN and pHTN among SCD patients. , More predictive power may arise from using multiple biomarkers simultaneously or from predicting the co-occurrence of SCDN and pHTN, although this has not previously been considered in the context of SCD.…”