Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia
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Summary: 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‐ PH a SST ) 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‐ PH a SST 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 .
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SCD patients with higher hemolysis rates have lower steady-state hemoglobin and are more likely to develop vascular injury and organ dysfunction with age, including pulmonary hypertension, diastolic left heart disease, and renal dysfunction.
“Patients with higher rates of hemolysis have lower steady-state Hb levels and are more likely to develop vascular injury and organ dysfunction as they age, manifesting as pulmonary hypertension, diastolic left heart disease, and renal dysfunction (proteinuria, albuminuria, and chronic kidney dysfunction) (62, 64, 65, 70, 79).”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [70]
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Experimental — accuracy not yet measuredThe kidneys are among the most commonly affected organs in patients with sickle cell disease.
“The kidneys are among the most commonly affected organs in patients with SCD (70, 201)”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [70]
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Gene Therapies for Sickle Cell Disease
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Self-citationKidney function after nonmyeloablative hematopoietic cell transplant for sickle cell disease
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Self-citation
- Authors
- Saraf, S. L., Zhang, X., Kanias, T., Lash, J. P., Molokie, R. E., Oza, B., Lai, C., Rowe, J. H., Gowhari, M., Hassan, J., DeSimone, J., Machado, R. F., Gladwin, M. T., Little, J. A., & Gordeuk, V. R.
- Affiliations
- University of Illinois Chicago (US)
- University of Pittsburgh (US)
- Case Western Reserve University (US)
- Corresponding author
- Saraf, Santosh L.
- ORCID
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2013-12-12
- Volume
- 164
- Issue
- 5
- Pages
- 729-739
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- PMC
- PMC3945021
- OpenAlex
- W2087355617
- Cited by
- 120
- References
- 51
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 5 · 2022: 12 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 14 · 2017: 17 · 2016: 9 · 2015: 14 · 2014: 6
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services (R01HL111656)
- National Institutes of Health (KL2TR000048)
- National Heart, Lung, and Blood Institute (R01HL096973, K23HL098454, P01HL103455, HHSN268200617182C, R01HL098032, R01HL111656)
- National Institute of Diabetes and Digestive and Kidney Diseases (L30 DK099990, K24DK092290)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- hemoglobinuria, sickle cell disease, chronic kidney disease, chronic kidney disease progression, intravascular hemolysis, lactate dehydrogenase, albuminuria, estimated glomerular filtration rate, dialysis requirement, thalassemia, renal dysfunction
- MeSH terms
- Adult, Albuminuria, Anemia, Sickle Cell, Female, Follow-Up Studies, Glomerular Filtration Rate, Hemoglobins, Hemoglobinuria, Humans, Male, Middle Aged, Severity of Illness Index, Disease Progression, Renal Insufficiency, Chronic, Young Adult
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