History of Asthma is Associated with Albuminuria within an International Pediatric Cohort of Sickle Cell Disease Patients: A Casire Group Analysis

Background: Renal disease is a common end organ complication of sickle cell disease(SCD). Risk factors of sickle cell nephropathy include age, genotype, and anemia. We have investigated and discovered Lower Hemoglobin Oxygen Saturation levels associated with microalbuminuria. To further investigate this, we investigated a patient's history of asthma as a risk factor of renal disease. Asthma has been linked to increased mortality in adult and children with SCD from the National Cooperative SCD Study Group. In our ongoing International CASIRE Renal Cohort study, we investigated the clinical history of asthma and laboratory correlates of albuminuria and proteinuria as measured by Urine Protein/Creatinine and Urine Albumin/Creatinine .

Methods: 538pediatric and adult SCD (3-59 y/o) patients were recruited at baseline from 6 Centers (USA: Univ of Michigan, Case Medical Center/Rainbow Babies, Albert Einstein-Montefiore Medical Center, Univ of Connecticut; Italy: Univ. of Padova, Univ of Naples;). Clinical history and laboratory studies, including Pain crisis patterns, SBP, DBP, BMI, CBC, Serum Crt, Urine ph, Urine SG were collected. For this report, we concentrated on patient's comorbidities and sickle cell medical history, specifically pain crisis patterns, acute chest history and asthma. Urine Microalbumin/Crt(UMA) (mg/gm) was obtained in 172 patients and we categorized patients into No Albuminuria: (No UMA)<30mg/gm and Albuminuria(UMAlbum): Microalbuminuria(MicroUMA) 30-299mg/gm and Macroalbuminuria (MacroUMA)>300mg/gm.334 subjects answered the question of medical history of asthma and of those 172 had Urine Microalbumin (UMA) levels. 75% of SCD-Asthma group (N=56) and 78% of SCD-NoAsthma group (N=204) had severe SCD (SS or SBeta Zero). Children (<18y/o) comprised 58% of the SCD-Asthma group (N=43) and 62% of the SCD-NoAsthma group (N=161). Mean age was 16 y/o in both SCD-Asthma and SCD-NoAsthma Groups.

Results: No Albuminuria (NoUMAlbum) was reported in 80% (138/172) while Albuminuria(UMAlbum) was recorded in 20% (34/172) of the Cohort. Severe SCD pts represented 91% (n=33) of the Albuminuria pts. Adult UMA levels were higher (mean=61) than Peds UMA levels (mean=22) (p=0.025). Patients with History of Asthma had higher mean UMA levels ( 94 vs 21, p=0.005). Further, a history of asthma was associated with higher mean UMA levels (122 vs 23, p=0.003) within the Severe Genotype group (p=0.002), within all Pediatric SCD patients ( 60 vs 17, p=0.002), and within Severe Pediatric SCD patients ( 68 vs 19, p=0.004) (One Way Anova). Within the Medical history, BMI in the underweight range and a history of priapism were associated with elevated UMA levels.

Conclusions: Age and Severe Genotype was associated with Albuminuria. A history of asthma was strongly associated with renal disease in Pediatric SCD patients in addition to a very strong association within Pediatric Severe Genotype patients. Optimal control of asthma could possibly mitigate the risk of kidney disease with SCD patients. A more in-dept analysis of patient's history of asthma would provide stronger evidence of these findings.