Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia

Santosh L. Saraf, Xu Zhang, Tamir Kanias, James P. Lash, Robert E. Molokie, Bharvi Oza, Catherine Lai, Julie H. Rowe, Michel Gowhari, Johara Hassan, Joseph Desimone, Roberto Machado, Mark T. Gladwin, Jane A. Little, Victor R. Gordeuk

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Summary: To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβo 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.

Original languageEnglish (US)
Pages (from-to)729-739
Number of pages11
JournalBritish Journal of Haematology
Volume164
Issue number5
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

Fingerprint

Hemoglobinuria
Sickle Cell Anemia
Chronic Renal Insufficiency
Disease Progression
Pulmonary Hypertension
Confidence Intervals
Sickle Hemoglobin
Kidney
Albuminuria
Thalassemia
Kidney Diseases
Therapeutics
Hemolysis
Glomerular Filtration Rate
Heme
L-Lactate Dehydrogenase
Dialysis
Microscopy
Erythrocytes
Enzyme-Linked Immunosorbent Assay

Keywords

  • Albuminuria
  • Haemoglobinuria
  • Haemolysis
  • Kidney disease
  • Sickle cell

ASJC Scopus subject areas

  • Hematology

Cite this

Saraf, S. L., Zhang, X., Kanias, T., Lash, J. P., Molokie, R. E., Oza, B., ... Gordeuk, V. R. (2014). Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia. British Journal of Haematology, 164(5), 729-739. https://doi.org/10.1111/bjh.12690

Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia. / Saraf, Santosh L.; Zhang, Xu; Kanias, Tamir; Lash, James P.; Molokie, Robert E.; Oza, Bharvi; Lai, Catherine; Rowe, Julie H.; Gowhari, Michel; Hassan, Johara; Desimone, Joseph; Machado, Roberto; Gladwin, Mark T.; Little, Jane A.; Gordeuk, Victor R.

In: British Journal of Haematology, Vol. 164, No. 5, 01.03.2014, p. 729-739.

Research output: Contribution to journalArticle

Saraf, SL, Zhang, X, Kanias, T, Lash, JP, Molokie, RE, Oza, B, Lai, C, Rowe, JH, Gowhari, M, Hassan, J, Desimone, J, Machado, R, Gladwin, MT, Little, JA & Gordeuk, VR 2014, 'Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia', British Journal of Haematology, vol. 164, no. 5, pp. 729-739. https://doi.org/10.1111/bjh.12690
Saraf, Santosh L. ; Zhang, Xu ; Kanias, Tamir ; Lash, James P. ; Molokie, Robert E. ; Oza, Bharvi ; Lai, Catherine ; Rowe, Julie H. ; Gowhari, Michel ; Hassan, Johara ; Desimone, Joseph ; Machado, Roberto ; Gladwin, Mark T. ; Little, Jane A. ; Gordeuk, Victor R. / Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia. In: British Journal of Haematology. 2014 ; Vol. 164, No. 5. pp. 729-739.
@article{150354d7970e4d7f92d8493cd1ea45e9,
title = "Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia",
abstract = "Summary: To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβo 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.",
keywords = "Albuminuria, Haemoglobinuria, Haemolysis, Kidney disease, Sickle cell",
author = "Saraf, {Santosh L.} and Xu Zhang and Tamir Kanias and Lash, {James P.} and Molokie, {Robert E.} and Bharvi Oza and Catherine Lai and Rowe, {Julie H.} and Michel Gowhari and Johara Hassan and Joseph Desimone and Roberto Machado and Gladwin, {Mark T.} and Little, {Jane A.} and Gordeuk, {Victor R.}",
year = "2014",
month = "3",
day = "1",
doi = "10.1111/bjh.12690",
language = "English (US)",
volume = "164",
pages = "729--739",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia

AU - Saraf, Santosh L.

AU - Zhang, Xu

AU - Kanias, Tamir

AU - Lash, James P.

AU - Molokie, Robert E.

AU - Oza, Bharvi

AU - Lai, Catherine

AU - Rowe, Julie H.

AU - Gowhari, Michel

AU - Hassan, Johara

AU - Desimone, Joseph

AU - Machado, Roberto

AU - Gladwin, Mark T.

AU - Little, Jane A.

AU - Gordeuk, Victor R.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Summary: To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβo 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.

AB - Summary: To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβo 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.

KW - Albuminuria

KW - Haemoglobinuria

KW - Haemolysis

KW - Kidney disease

KW - Sickle cell

UR - http://www.scopus.com/inward/record.url?scp=84894046080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894046080&partnerID=8YFLogxK

U2 - 10.1111/bjh.12690

DO - 10.1111/bjh.12690

M3 - Article

C2 - 24329963

AN - SCOPUS:84894046080

VL - 164

SP - 729

EP - 739

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 5

ER -