Advertisement

Sickle Cell Disease and Kidney

      Sickle cell disease causes several kidney manifestations. They include defects in urine concentration, impaired handling of potassium and hydrogen ion, albuminuria, acute kidney injury, and chronic kidney disease to name a few. Glomerular hyperfiltration, tubular hyperfunctioning, endothelial damage from repeated sickling and vaso-occlusive episodes, and iron-induced proinflammatory changes in the glomerular mesangium and tubulointerstitium are some of the mechanisms of kidney damage. Albuminuria is one of the most and common clinical features of kidney disease and progresses with age. Kidney disease in patients with sickle cell is associated with increased mortality. Annual screening for proteinuria starting at age 10 years and limiting the use of nonsteroidal anti-inflammatory agents and the use of angiotensin-converting enzyme inhibitors may help in early detection and delaying the progression of kidney disease. Adequate hydration, angiotensin-converting enzyme inhibitors, and adequate control of sickle cell are the main stay of treatment for albuminuria. The hemoglobin goal for patients with sickle cell nephropathy is lesser (10 g/dL) than that for patients with chronic kidney disease due to other causes given that a higher hemoglobin level increases viscosity and the risk of precipitating vaso-occlusive episodes. A multidisciplinary approach is recommended for managing patients with sickle cell and kidney diseases.

      Graphical abstract

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Advances in Chronic Kidney Disease
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kato G.J.
        • Piel F.B.
        • Reid C.D.
        • et al.
        Sickle cell disease.
        Nat Rev Dis Primers. 2018; 4 (18010): 1-22
        • Piel F.B.
        • Steinberg M.H.
        • Rees D.C.
        Sickle cell disease.
        N Engl J Med. 2017; 376: 1561-1573
        • Frenette P.S.
        • Atweh G.F.
        Sickle cell disease: old discoveries, new concepts, and future promise.
        J Clin Invest. 2007; 117: 850-858
        • Gurbanov K.
        • Rubinstein I.
        • Hoffman A.
        • Abassi Z.
        • Better O.S.
        • Winaver J.
        Differential regulation of renal regional blood flow by endothelin-1.
        Am J Physiol. 1996; 271: F1166-F1172
        • Nath K.A.
        • Grande J.P.
        • Haggard J.J.
        • et al.
        Oxidative stress and induction of heme oxygenase-1 in the kidney in sickle cell disease.
        Am J Pathol. 2001; 158: 893-903
        • Naik R.P.
        • Derebail V.K.
        The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait.
        Expert Rev Hematol. 2017; 10: 1087-1094
        • Ataga K.I.
        • Brittain J.E.
        • Moore D.
        • et al.
        Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: potential role of soluble fms-like tyrosine kinase-1.
        Eur J Haematol. 2010; 85: 257-263
        • Nath K.A.
        • Hebbel R.P.
        Sickle cell disease: renal manifestations and mechanisms.
        Nat Rev Nephrol. 2015; 11: 161-171
        • Drawz P.
        • Ayyappan S.
        • Nouraie M.
        • et al.
        Kidney disease among patients with sickle cell disease, hemoglobin SS and SC.
        Clin J Am Soc Nephrol. 2016; 11: 207-215
        • Guasch A.
        • Navarrete J.
        • Nass K.
        • et al.
        Glomerular involvement in adults with sickle cell hemoglobinopathies: prevalence and clinical correlates of progressive renal failure.
        J Am Soc Nephrol. 2006; 17: 2228-2235
        • Guasch A.
        • Zayas C.F.
        • Eckman J.R.
        • et al.
        Evidence that microdeletions in the alpha globin gene protect against the development of sickle cell glomerulopathy in humans.
        J Am Soc Nephrol. 1999; 10: 1014-1019
        • Saraf S.L.
        • Shah B.N.
        • Zhang X.
        • et al.
        APOL1, α-thalassemia, and BCL11A variants as a genetic risk profile for progression of chronic kidney disease in sickle cell anemia.
        Haematologica. 2017; 102: e1-e6
        • Ashley-Koch A.E.
        • Okocha E.C.
        • Garrett M.E.
        • et al.
        MYH9 and APOL1 are both associated with sickle cell disease nephropathy.
        Br J Haematol. 2011; 155: 386-394
        • Nolan V.G.
        • Ma Q.
        • Cohen H.T.
        • et al.
        Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B.
        Am J Hematol. 2007; 82: 179-184
        • Statius van Eps L.W.
        • Pinedo-Veels C.
        • de Vries G.H.
        • de Koning J.
        Nature of concentrating defect in sickle-cell nephropathy.
        Microradioangiographic Studies Lancet. 1970; 1: 450-452
        • Statius van Eps L.W.
        • Schouten H.
        • La Porte-Wijsman L.W.
        • Struyker Boudier A.M.
        The influence of red blood cell transfusions on the hyposthenuria and renal hemodynamics of sickle cell anemia.
        Clin Chim Acta. 1967; 17: 449-461
        • Sharpe C.C.
        • Thein S.L.
        Sickle cell nephropathy - a practical approach.
        Br J Haematol. 2011; 155: 287-297
        • Maurel S.
        • Stankovic Stojanovic K.
        • Avellino V.
        • et al.
        Prevalence and correlates of metabolic acidosis among patients with homozygous sickle cell disease.
        Clin J Am Soc Nephrol. 2014; 9: 648-653
        • DeFronzo R.A.
        • Taufield P.A.
        • Black H.
        • McPhedran P.
        • Cooke C.R.
        Impaired renal tubular potassium secretion in sickle cell disease.
        Ann Intern Med. 1979; 90: 310-316
        • Batlle D.
        • Itsarayoungyuen K.
        • Arruda J.A.
        • Kurtzman N.A.
        Hyperkalemic hyperchloremic metabolic acidosis in sickle cell hemoglobinopathies.
        Am J Med. 1982; 72: 188-192
        • Cazenave M.
        • Audard V.
        • Bertocchio J.P.
        • et al.
        Tubular acidification defect in adults with sickle cell disease.
        Clin J Am Soc Nephrol. 2020; 15: 16-24
        • Kiryluk K.
        • Jadoon A.
        • Gupta M.
        • Radhakrishnan J.
        Sickle cell trait and gross hematuria.
        Kidney Int. 2007; 71: 706-710
        • Sharpe C.C.
        • Thein S.L.
        How I treat renal complications in sickle cell disease.
        Blood. 2014; 123: 3720-3726
        • Pegelow C.H.
        • Colangelo L.
        • Steinberg M.
        • et al.
        Natural history of blood pressure in sickle cell disease: risks for stroke and death associated with relative hypertension in sickle cell anemia.
        Am J Med. 1997; 102: 171-177
        • Ware R.E.
        • Rees R.C.
        • Sarnaik S.A.
        • et al.
        Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial.
        J Pediatr. 2010; 156: 66-70
        • Aygun B.
        • Mortier N.A.
        • Smeltzer M.P.
        • Shulkin B.L.
        • Hankins J.S.
        • Ware R.E.
        Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia.
        Am J Hematol. 2013; 88: 116-119
        • Derebail V.K.
        • Ciccone E.J.
        • Zhou Q.
        • Kilgore R.R.
        • Cai J.
        • Ataga K.I.
        Progressive decline in estimated GFR in patients with sickle cell disease: an Observational cohort study.
        Am J Kidney Dis. 2019; 74: 47-55
        • Maigne G.
        • Ferlicot S.
        • Galacteros F.
        • et al.
        Glomerular lesions in patients with sickle cell disease.
        Medicine (Baltimore). 2010; 89: 18-27
        • Niss O.
        • Lane A.
        • Asnani M.R.
        • et al.
        Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study.
        Blood Adv. 2020; 4: 1501-1511
        • Quek L.
        • Sharpe C.
        • Dutt N.
        • et al.
        Acute human parvovirus B19 infection and nephrotic syndrome in patients with sickle cell disease.
        Br J Haematol. 2010; 149: 289-291
        • Ataga K.I.
        • Derebail V.K.
        • Archer D.R.
        The glomerulopathy of sickle cell disease.
        Am J Hematol. 2014; 89: 907-914
        • Gosmanova E.O.
        • Zaidi S.
        • Wan J.Y.
        • et al.
        Prevalence and progression of chronic kidney disease in adult patients with sickle cell disease.
        J Investig Med. 2014; 62: 804-807
        • Naik R.P.
        • Irvin M.R.
        • Judd S.
        • et al.
        Sickle cell trait and the risk of ESRD in blacks.
        J Am Soc Nephrol. 2017; 28: 2180-2187
        • Abbott K.C.
        • Hypolite I.O.
        • Agodoa L.Y.
        Sickle cell nephropathy at end-stage renal disease in the United States: patient characteristics and survival.
        Clin Nephrol. 2002; 58: 9-15
        • McClellan A.C.
        • Luthi J.C.
        • Lynch J.R.
        • et al.
        High one year mortality in adults with sickle cell disease and end-stage renal disease.
        Br J Haematol. 2012; 159: 360-367
        • Quinn C.T.
        • Rogers Z.R.
        • McCavit T.L.
        • Buchanan G.R.
        Improved survival of children and adolescents with sickle cell disease.
        Blood. 2010; 115: 3447-3452
        • Bae S.
        • Johnson M.
        • Massie A.B.
        • et al.
        Mortality and access to kidney transplantation in patients with sickle cell disease-associated kidney failure.
        Clin J Am Soc Nephrol. 2021; 16: 407-414
        • Audard V.
        • Homs S.
        • Habibi A.
        • et al.
        Acute kidney injury in sickle patients with painful crisis or acute chest syndrome and its relation to pulmonary hypertension.
        Nephrol Dial Transpl. 2010; 25: 2524-2529
        • Pham P.T.
        • Pham P.C.
        • Wilkinson A.H.
        • Lew S.Q.
        Renal abnormalities in sickle cell disease.
        Kidney Int. 2000; 57: 1-8
        • Olaniran K.O.
        • Allegretti A.S.
        • Zhao S.H.
        • Nigwekar S.U.
        • Kalim S.
        Acute kidney injury among Black patients with sickle cell trait and sickle cell disease.
        Clin J Am Soc Nephrol. 2021; 16: 348-355
        • Cecchini J.
        • Lionnet F.
        • Djibré M.
        • et al.
        Outcomes of adult patients with sickle cell disease admitted to the ICU: a case series.
        Crit Care Med. 2014; 42: 1629-1639
        • Yawn B.P.
        • Buchanan G.R.
        • Afenyi-Annan A.N.
        • et al.
        Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members [published correction appears in JAMA. 2014 Nov 12;312(18):1932] [published correction appears in JAMA. 2015 Feb 17;313(7):729].
        JAMA. 2014; 312: 1033-1048
        • Expert Panel NHLBI
        Evidence-based management of sickle cell disease.
        • Voskaridou E.
        • Terpos E.
        • Michail S.
        • et al.
        Early markers of renal dysfunction in patients with sickle cell/beta-thalassemia.
        Kidney Int. 2006; 69: 2037-2042
        • Laurentino M.R.
        • Parente Filho S.L.A.
        • Parente L.L.C.
        • da Silva Júnior G.B.
        • Daher E.F.
        • Lemes R.P.G.
        Non-invasive urinary biomarkers of renal function in sickle cell disease: an overview.
        Ann Hematol. 2019; 98: 2653-2660
        • Castro-Sesquen Y.E.
        • Saraf S.L.
        • Gordeuk V.R.
        • Nekhai S.
        • Jerebtsova M.
        Use of Multiple urinary biomarkers for early detection of chronic kidney disease in sickle cell anemia patients.
        Blood. 2020; 136: 30
        • Liem R.I.
        • Lanzkron S.
        • D Coates T.
        • et al.
        American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease.
        Blood Adv. 2019; 3: 3867-3897
        • Quinn C.T.
        • Saraf S.L.
        • Gordeuk V.R.
        • et al.
        Losartan for the nephropathy of sickle cell anemia: a phase-2, multicenter trial.
        Am J Hematol. 2017; 92: E520-E528
      1. Losartan for sickle cell kidney disease (SCD-Losartan) ClinicalTrials.gov identifier: NCT01989078.
        • Telen M.J.
        Curative vs targeted therapy for SCD: does it make more sense to address the root cause than target downstream events?.
        Blood Adv. 2020; 4: 3457-3465
      2. A Voxelotor for sickle cell anemia patients at highest risk for progression of chronic kidney disease. ClinicalTrials.gov Identifier: NCT04335721.
      3. Study exploring the effect of Crizanlizumab on kidney function in patients with chronic kidney disease caused by sickle cell disease. ClinicalTrials.gov Identifier: NCT04053764.
        • Hoppe C.
        • Neumayr L.
        Sickle cell disease: monitoring, Current treatment, and Therapeutics under development.
        Hematol Oncol Clin North Am. 2019; 33: 355-371
        • Boyle S.M.
        • Jacobs B.
        • Sayani F.A.
        • Hoffman B.
        Management of the dialysis patient with sickle cell disease.
        Semin Dial. 2016; 29: 62-70
        • Ojo A.O.
        • Govaerts T.C.
        • Schmouder R.L.
        • et al.
        Renal transplantation in end-stage sickle cell nephropathy.
        Transplantation. 1999; 67: 291-295
        • Okafor U.H.
        • Aneke E.
        Outcome and challenges of kidney transplant in patients with sickle cell disease.
        J Transpl. 2013; 2013: 614610
        • Nath J.
        • McDaid J.
        • Bentall A.
        • Ball S.
        • Ready A.R.
        • Inston N.G.
        Sickle cell and renal transplant: a national survey and literature review.
        Exp Clin Transpl. 2012; 10: 1-7
        • Willis J.C.
        • Awogbade M.
        • Howard J.
        • et al.
        Outcomes following kidney transplantation in patients with sickle cell disease: the impact of automated exchange blood transfusion.
        PLoS One. 2020; 15: e0236998
        • Hosoya H.
        • Levine J.
        • Abt P.
        • Henry D.
        • Porter D.L.
        • Gill S.
        Toward dual hematopoietic stem-cell transplantation and solid-organ transplantation for sickle-cell disease.
        Blood Adv. 2018; 2: 575-585