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      Sickle cell disease and albuminuria: recent advances in our understanding of sickle cell nephropathy

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          Albuminuria is considered to be a relevant biomarker for the detection of early glomerular damage in patients with sickle cell disease (SCD). Improvements in our understanding of the pathophysiological processes and molecular mechanisms underlying albuminuria are required, because increasing numbers of patients with SCD are developing chronic kidney disease. The early recognition of sickle cell nephropathy (SCN) and studies of the natural course of this emerging renal disease are therefore crucial, together with identification of the associated clinical and biological risk factors, to make it possible to initiate kidney-protective therapy at early stages of renal impairment. The pathophysiological process underlying SCN remains hypothetical, but chronic haemolysis-related endothelial dysfunction and the relative renal hypoxia triggered by repeated vaso-occlusive crises have been identified as two potential key factors. The optimal preventive and curative management of albuminuria in the context of SCD is yet to be established, but recent studies have suggested that hydroxyurea therapy, the cornerstone of SCD treatment, could play a key role in reducing albuminuria. The place of conventional kidney-protecting measures, such as renin–angiotensin system inhibitors, in the treatment of SCD patients also remains to be determined.

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          Most cited references 36

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          Hydroxyurea for the treatment of sickle cell anemia.

           Manu Platt (2008)
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            Sickle cell disease: renal manifestations and mechanisms.

            Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ(+)-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16-18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms.
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              Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme.

              Nephropathy may develop in patients with sickle cell disease. We determined the prevalence of proteinuria and renal insufficiency in a group of patients with sickle cell disease and investigated the renal pathologic changes and the effects of an angiotensin-converting-enzyme inhibitor (enalapril) on protein excretion in patients found to have nephropathy. We prospectively screened 381 patients with sickle cell disease for the presence of proteinuria and renal insufficiency. Renal biopsy and measurements of glomerular filtration rate, effective renal plasma flow, and urinary protein excretion were performed in 10 patients with mild nephropathy before and after the administration of enalapril, and again two to three weeks after its discontinuation. Of the 381 patients with sickle cell disease, 26 (7 percent) had serum creatinine concentrations above the normal range and 101 (26 percent) had proteinuria of at least 1+. The renal lesions in the 10 patients who had biopsies consisted of glomerular enlargement and perihilar focal segmental glomerulosclerosis. The mean (+/- SD) glomerular area in these patients was 28.7 +/- 4.1 x 10(3) micron 2, as compared with 15.8 +/- 4.3 x 10(3) micron 2 in 10 control patients without renal disease who had died of trauma (P less than 0.0001). During the administration of enalapril, the mean 24-hour urinary protein excretion decreased 57 percent (range, 23 to 79 percent) below the base-line value (P less than 0.001), and it increased to 25 percent below the base-line value after enalapril was discontinued. The glomerular filtration rate and effective renal plasma flow did not change significantly. Approximately 25 percent of patients with sickle cell disease have proteinuria. Treatment with enalapril reduces the degree of proteinuria in these patients, suggesting that glomerular capillary hypertension may be a pathogenic factor in sickle cell nephropathy.

                Author and article information

                Clin Kidney J
                Clin Kidney J
                Clinical Kidney Journal
                Oxford University Press
                August 2017
                21 April 2017
                21 April 2017
                : 10
                : 4
                : 475-478
                [1 ]Service de Néphrologie et Transplantation, Institut Francilien de Recherche en Néphrologie et Transplantation (IFRNT), Groupe Hospitalier Henri Mondor-Albert Chenevier, Assistance Publique–Hôpitaux de Paris (APHP), Université Paris-Est Créteil (UPEC), Créteil, France
                [2 ]Unité INSERM U955, Equipe 21, Centre de Référence Syndrome Néphrotique Idiopathique, UPEC, Créteil, France
                [3 ]Centre de Référence des Syndromes Drépanocytaires Majeurs, Groupe Hospitalier Henri Mondor-Albert Chenevier, APHP, UPEC, Créteil, France
                [4 ]Service de Médecine Interne, Groupe Hospitalier Henri Mondor-Albert Chenevier, APHP, UPEC, Créteil, France
                [5 ]Unité INSERM 955, Equipe 2 émergente, UPEC, Créteil, France
                [6 ]Laboratoire of Excellence GR-Ex, Paris, France
                Author notes
                [* ]Correspondence and offprint requests to: Vincent Audard; E-mail: vincent.audard@
                © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact

                Page count
                Pages: 4
                Genetic Kidney Disease


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