Proteinuria in adults with sickle-cell disease: the role of hydroxycarbamide(hydroxyurea) as a protective agent

Silva, Geraldo Bezerra da; Vieira, Ana Patrícia Freitas; Couto, Amanda X.; Alves, Marília P.; Meneses, Gdayllon Cavalcante; Martins, Alice Maria Costa; Araújo, Sônia Maria Holanda Almeida; Liborio, Alexandre; Daher, Elizabeth F.

doi:10.1007/s11096-014-9955-4

Cited by 14 publications

(8 citation statements)

References 16 publications

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“…We did not find significant differences in creatinine, urine osmolality, cystatin C, or estimated GFR, suggesting that renal pathology may have been too far advanced or that 1 year was not sufficient to reverse these kidney parameters. However, similar to other studies, hydroxyurea significantly decreased albuminuria in our patients 45,46,49,50 . In fact, of 3 patients with macroalbuminuria at baseline, protein levels decreased to the microalbuminuria range in 1 patient and no albuminuria range in 1 patient.…”

Section: Discussionsupporting

confidence: 91%

“…Hydroxyurea has been reported to decrease cortical iron kidney deposits in a patient with SCD 44 . Further, hydroxyurea has been shown to prospectively decrease proteinuria in adults and children with SCD 45,46 and was associated with a lower prevalence of albuminuria in adults with SCD 47 . Although hydroxyurea dosed at MTD significantly decreased GFR in children with SCD, there was no significant change in cystatin C levels, and a randomized, placebo‐controlled trial of fixed dose hydroxyurea (20 mg/kg/day) in infants did not show improvement in GFR between those receiving hydroxyurea versus placebo 11 ; however, infants receiving hydroxyurea had significantly higher urine osmolality and decreased kidney enlargement, implying some benefit to the kidneys 48 .…”

Section: Discussionmentioning

confidence: 96%

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Computer Algorithm‐Based Hydroxyurea Dosing Facilitates Titration to Maximum Tolerated Dose in Sickle Cell Anemia

Oldham

Conrey

Pittman

et al. 2020

The Journal of Clinical Pharma

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Adults with sickle cell disease (SCD) experience acute and chronic complications and die prematurely. When taken at maximum tolerated dose (MTD), hydroxyurea prolongs survival; however, it has not consistently reversed organ dysfunction. Patients also frequently do not take hydroxyurea, at least in part because of physician discomfort with prescribing hydroxyurea. We sought to develop a computer program that could easily titrate hydroxyurea to MTD. This was a single-arm, open-label pilot study. Fifteen patients with homozygous SCD were enrolled in the protocol, and 10 patients were followed at baseline and then for 1 year after hydroxyurea initiation or dose titration. Fetal hemoglobin significantly increased in all 10 patients from 8.3% to 25.1% (P < .001). Nine patients were titrated to MTD in an average of 7.9 months, and the tenth patient's hydroxyurea dose was increased to 33 mg/kg/day. Computer program dosing recommendations were the same as manual dosing decisions made using the same algorithm for all patients and at all times. We also evaluated markers of cardiopulmonary, liver and renal damage. Although cardiopulmonary function did not significantly improve, direct bilirubin and alanine aminotransferase levels significantly decreased (P < .001 and P < .01, respectively). Last, although kidney function did not improve, degree of proteinuria was significantly reduced (P < .05). We have developed a computer program that reliably titrates hydroxyurea to MTD. A larger study is indicated to test the program either as a computer program or a downloadable application.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Computer Algorithm‐Based Hydroxyurea Dosing Facilitates Titration to Maximum Tolerated Dose in Sickle Cell Anemia

Oldham

Conrey

Pittman

et al. 2020

The Journal of Clinical Pharma

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“…Approximately 12% of patients with SCD have chronic renal failure, which is associated with significant morbidity and mortality 9. Use of hydroxyurea may be beneficial to prevent the progression of sickle cell nephropathy10 by decreasing the degree of proteinuria,11 which is perhaps correlated with increased Haemoglobin F 12. Hydroxyurea reduces the production of RBCs with predominant Haemoglobin S by inhibiting ribonucleotide reductase, with subsequent compensatory increase in RBC with Haemoglobin F formation by activating the γ- gene 4.…”

Section: Discussionmentioning

confidence: 99%

A predictable but life-threatening complication of hydroxyurea in a patient with sickle cell anaemia: an experience learned from a Jehovah's Witness

et al. 2015

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It is well known that hydroxyurea can cause pancytopaenia secondary to bone marrow suppression, which is reversible with short-term discontinuation of the therapy. However, it is important to note that bone marrow suppressive effects caused by hydroxyurea could be easily potentiated in patients with sickle cell anaemia complicated by chronic kidney disease (CKD). We present a case of a Jehovah's Witness with sickle cell anaemia, who developed severe bone marrow suppression due to the combined effects of hydroxyurea and CKD, resulting in a prolonged recovery period after discontinuation of hydroxyurea.

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“…The use of hydroxyurea (HU) has been suggested to reduce proteinuria and hyperfiltration as suggested in one prospective study consisting of 26 patients with SCD. However, no effect on microalbuminuria was found [77,149]. A cross-sectional study of 149 adult patients showed that those using hydroxyurea were less likely to exhibit albuminuria (defined as urinary urinary-creatinine ratios ≥30 mg/g) [149].…”

Section: Treatment Of Proteinuriamentioning

confidence: 99%

“…However, no effect on microalbuminuria was found [77,149]. A cross-sectional study of 149 adult patients showed that those using hydroxyurea were less likely to exhibit albuminuria (defined as urinary urinary-creatinine ratios ≥30 mg/g) [149]. A multi-center trial in infants (mean age 13.8 months) demonstrated that treatment with hydroxyurea for 24 months did not influence the GFR.…”

Section: Treatment Of Proteinuriamentioning

confidence: 99%

Sickle Cell Nephropathy: Current Understanding of the Presentation, Diagnostic and Therapeutic Challenges

Inusa¹,

Lodi²,

Palazzi³

et al. 2018

Hematology - Latest Research and Clinical Advances

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Sickle cell nephopathy (SCN) begins early in childhood from failure of urinary concentration (hyposthenuria), albuminuria to hyperfiltration, hematuria and progression to falling glomerular filtration to end-stage renal disease and increased mortality. Renal involvement is more severe in homozygous individuals (HbSS) than in compound heterozygous patients (HbSC). The pathogenesis of SCN is multifactorial from hypoxia, acidosis, hemolysis, ischemia-reperfusion injury and albuminuria. The clinical manifestations depend on whether the main pathology is tubular, glomerular or a mixture of both abnormalities. This chapter offers a critical review of the recent literature and will highlight the pathophysiology, epidemiology, clinical manifestations and management of sickle cell nephropathy with particular focus on the major advance in the early diagnosis. Learning points: For SCN, the onset of hyperfiltration and albuminuria in infants and childhood is an opportunity to intervene early. There is no diagnostic markertest capable of detecting the onset of these changes. Moreover there is no reliable therapeutic agent to prevent or halt early changes due to SCN. The development of a marker of renal impairment in SCD such as such as Cystatin C assay if validated may be appropriate for wider clinical application.

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Proteinuria in adults with sickle-cell disease: the role of hydroxycarbamide(hydroxyurea) as a protective agent

Abstract: SCD is associated with important renal abnormalities. Hydroxycarbamide seems to protect kidney function in SCD by decreasing proteinuria but not microalbuminuria.

Cited by 14 publications

References 16 publications

Computer Algorithm‐Based Hydroxyurea Dosing Facilitates Titration to Maximum Tolerated Dose in Sickle Cell Anemia

Computer Algorithm‐Based Hydroxyurea Dosing Facilitates Titration to Maximum Tolerated Dose in Sickle Cell Anemia

A predictable but life-threatening complication of hydroxyurea in a patient with sickle cell anaemia: an experience learned from a Jehovah's Witness

Sickle Cell Nephropathy: Current Understanding of the Presentation, Diagnostic and Therapeutic Challenges

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