Association between hemolysis and albuminuria in adults with sickle cell anemia

Abstract

We have investigated renal function and markers of hemolysis in a cohort of 424 adult African-British patients with sickle cell disease. While significant associations were found in HbSS and HbSb 0 (sickle cell anemia) patients with and without controlling for covariates between hemolytic markers and albuminuria, the associations were not significant in patients with HbSC. Estimated glomerular filtration rate, a marker of renal function, correlated significantly with reticulocyte count and bilirubin. Alpha thalassemia, present in 34% of the sickle cell anaemia patients, had a protective effect against albuminuria in this group. Altogether, the incidence of hyperfiltration was 71% and microalbuminuria 37%, making nephropathy a common complication of sickle cell anemia. Haematologica 2012;97(2):201-205. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACTexcluded from the study group if they had a history of diabetes mellitus, HIV infection, malignancy or another cause of chronic kidney disease (CKD) or if they were on a blood transfusion program. Seventeen patients were on ACE (angiotensin converting enzyme) inhibitor or ARB (angiotensin II receptor blocker) therapy; these patients were also excluded from the study. Since 2006, urinary albumin/creatinine ratio (ACR) has been a routine measurement for patients attending the specialist clinic. All patients were routinely genotyped for α thalassemia using a PCR-based methodology on DNA extracted from peripheral blood.17

Intravascular hemolysis and the pathophysiology of sickle cell disease

“…Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias. (24)(25)(26). In contrast, as mentioned earlier, other complications were associated with lower hemolysis rates and higher steady-state hemoglobin levels, including the rate of vaso-occlusive painful episodes, ACS, and osteonecrosis (Table 1).…”

A dose‐escalation phase IIa study of 2,2‐dimethylbutyrate (HQK‐1001), an oral fetal globin inducer, in sickle cell disease

“…The increase in total hemoglobin observed with HQK-1001 merits further evaluation as higher hemoglobin levels in SCD have been associated with fewer central nervous events, such as silent brain infarcts, and lower hemoglobin levels are associated with worse cognitive function in adults [38]. Furthermore, higher hemoglobin levels and decreased hemolysis have been associated with less vasculopathy and less albuminuria in SCD [39,40]. Based on the encouraging results of the present study, a multi-national placebo-controlled Phase II study was initiated in 2012 to determine if HQK-1001 administered as single agent at 30 mg/kg daily, for a longer period of time, results in higher Hb F response than seen in this study and would support the conduct of a large phase 3 study in SCD.…”

How I treat renal complications in sickle cell disease

“…3,5 In our patient cohort, both the incidence and degree of microalbuminuria are much lower in adults with HbSC disease when compared with HbSS or HbSb 0 . 6 Indeed, all our patients with HbSC disease and eGFR ,45 mL/min per 1.73 m 2 have a second renal diagnosis to account for their CKD, as in case 1. The other 2 major genetic modifiers are fetal Hb (HbF) levels and a-globin genotype.…”

“…In their cohort of 725 HbSS patients, Powars et al observed that no patient with .20% HbF had renal insufficiency. 1 Coinheritance of a thalassemia, present in 30% to 35% of SCD patients of African descent, delays the onset of microalbuminuria, 6 an effect ascribed to the ensuing reduction in hemolysis and complications related to nitric oxide-depleted vasculopathy.…”