Hemolysis & Hemoglobinuria Are Associated With Chronic Kidney Disease In Patients With Sickle Cell Anemia
thesisposted on 20.06.2014 by Santosh Saraf
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To evaluate the association between hemoglobinuria and chronic kidney disease (CKD) in sickle cell anemia (SCA), we analyzed 356 adult hemoglobin SS or Sβo thalassemia patients from the University of Illinois at Chicago and 439 from the multi-center Walk-PHaSST cohort. CKD was classified according to recommendations of the National Kidney Foundation. Hemoglobinuria was defined as positive heme on urine dipstick with absent red blood cells on microscopy and confirmed by direct hemoglobin measurement in a subset of patients. CKD outcomes included progression of CKD (halving of estimated glomerular filtration rate or requirement for dialysis or kidney transplant) and increase in albumin to creatinine ratio category (<30, 30-300, and > 300 mg/g creatinine). Hemoglobinuria was observed in 36% of UIC and 20% of Walk-PHaSST patients. Prevalence of CKD was 58% in the UIC cohort and 54% in the Walk-PHaSST cohort. Pathway analysis in both cohorts indicated an independent association of LDH with hemoglobinuria (P<0.0001) and, in turn, independent associations of hemoglobinuria (P<0.0001) and age (P<0.0001) with CKD. After a median of 32 months of follow-up, persistent hemoglobinuria was associated with progression of CKD (HR 4.0, 95%CI: 1.4-11.1; logrank P=0.0025) and worsening albuminuria category (HR 3.3, 95%CI: 1.6-5.3; logrank P=0.00013). In conclusion hemoglobinuria is common in SCA and is associated with CKD, suggesting a role for intravascular hemolysis in the pathogenesis of renal dysfunction in SCA.