title: Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia.
abstract: To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβ(o) thalassaemia patients from the University of Illinois at Chicago (UIC) and 439 from the multi-centre Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) cohort. CKD was classified according to National Kidney Foundation Kidney Disease Outcomes Quality Initiatives guidelines. Haemoglobinuria, defined as positive haem on urine dipstick with absent red blood cells on microscopy, was confirmed by enzyme-linked immunosorbent assay in a subset of patients. The prevalence of CKD was 58% in the UIC cohort and 54% in the Walk-PHaSST cohort, and haemoglobinuria was observed in 36% and 20% of the patients, respectively. Pathway analysis in both cohorts indicated an independent association of lactate dehydrogenase with haemoglobinuria and, in turn, independent associations of haemoglobinuria and age with CKD (P < 0·0001). After a median of 32 months of follow-up in the UIC cohort, haemoglobinuria was associated with progression of CKD [halving of estimated glomerular filtration rate or requirement for dialysis; Hazard ratio (HR) 13·9, 95% confidence interval (CI) 1·7-113·2, P = 0·0012] and increasing albuminuria (HR 3·1, 95% CI: 1·3-7·7; logrank P = 0·0035). In conclusion haemoglobinuria is common in SCA and is associated with CKD, consistent with a role for intravascular haemolysis in the pathogenesis of renal dysfunction in SCA.
authors: Section of Hematology-Oncology, Department of Medicine, Comprehensive Sickle Cell Center, University of Illinois at Chicago, Chicago, IL, USA.
authors: Santosh L
authors: SL
authors: Saraf
authors: Xu
authors: X
authors: Zhang
authors: Tamir
authors: T
authors: Kanias
authors: James P
authors: JP
authors: Lash
authors: Robert E
authors: RE
authors: Molokie
authors: Bharvi
authors: B
authors: Oza
authors: Catherine
authors: C
authors: Lai
authors: Julie H
authors: JH
authors: Rowe
authors: Michel
authors: M
authors: Gowhari
authors: Johara
authors: J
authors: Hassan
authors: Joseph
authors: J
authors: Desimone
authors: Roberto F
authors: RF
authors: Machado
authors: Mark T
authors: MT
authors: Gladwin
authors: Jane A
authors: JA
authors: Little
authors: Victor R
authors: VR
authors: Gordeuk
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000209:etiology; D000755:Anemia, Sickle Cell / Q000150:complications*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000378:metabolism; D006456:Hemoglobinuria / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D006454:Hemoglobins
keywords: albuminuria; haemoglobinuria; haemolysis; kidney disease; sickle cell