5613511 URINARY KIDNEY INJURY MOLECULE 1 AND URINARY MONOCYTE CHEMOTACTIC PROTEIN 1 AS NOVEL BIOMARKERS FOR EARLY DIAGNOSIS OF SICKLE CELL RENAL DYSFUNCTION

Abstract

Background: Sickle cell disease can affect the kidneys through multiple pathways leading to sickle cell nephropathy (SCN) which typically presents during early childhood. Unfortunately, accurate diagnosis of early SCN is difficult(1). Preclinical markers of glomerular damage in other conditions associated with hyperfiltration and hyperperfusion as microalbuminuria is still the early predictor of progressive renal nephropathy.Hence, it is necessary to discover new diagnostic biomarkers to facilitate the diagnosis of early stage SCN, enabling timely treatment and reducing related morbidity and mortality(2). Aim: To evaluate the role of urinary MCP-1 and KIM-1 as novel biomarkers for early detection of subclinicalSCN and to correlate these markers with other parameters of renal dysfunction, and with clinical and biochemical parameters for severity of SCD Methods: A one year prospective study including 45 children and adolescent diagnosed with SCD in their steady state for at least 3 month. SCD patients were divided based on the presence of microalbuminuria into patients with or without SCN.Routine kidney indices including estimated glomerular filtration rate and grade of nephropathy by ultrasound and the novel Urine MCP1 and urine KIM1 were measured and standardized for urine creatinine (ng/mg creatinine) compared to age and sex matched control. Results: It was found that there was statistically significant difference found between control group and SCD patients regarding the level of urine MCP-1 and urine KIM-1 with p-value <0.001.Also levels of urine MCP-1 and urine KIM-1 were higher in SCN group(n=32) compared to SCD without SCN (n=13)with p value <0.001. The best cut off point to differentiate between SCN group and other SCD without SCN was >300 ng/mg creatinine for urine MCP-1 with sensitivity 93.75 and specificity 76.92 and >2.8 ng/mg creatinine for urine KIM-1 with sensitivity 68.75 and specificity 100.Both level of urine MCP-1, urine KIM-1 were positively correlated with the duration of the disease(p<0.001, p,<0.001).Although urine MCP-1 correlated with the incidence of neurovascular events (p=0.026), urine KIM-1 correlated positively with vasoocclusive crisis frequency (p=0.011).Both markers correlated positively with serum and urine uric acid (p=0.000), grade of nephropathy by U/S (P=0.001)while negatively correlated with Egfr(p=0.018, p<0.001). There was a positive correlation between MCP-1, urine KIM-1 and deferasirox dose and duration (p<0.001, P=0.000) while non-significant with doses of deferoxamine and deferiprone. Conclusion: our data shows a distinct biomarker pattern in children with SCD, identifying KIM-1 and MCP-1 as two potential biomarkers of early detection SCN especially those on deferasirox. The appropriate chelation and proper monitoring of these patients is needed for for early diagnosis of nephropathy and timely intervention.