Skip to main content

Advertisement

SpringerLink
Log in

Sickle cell nephropathy: insights into the pediatric population

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The life expectancy of individuals with sickle cell disease has increased over the years, majorly due to an overall improvement in diagnosis and medical care. Nevertheless, this improved longevity has resulted in an increased prevalence of chronic complications such as sickle cell nephropathy (SCN), which poses a challenge to the medical care of the patient, shortening the lifespan of patients by 20–30 years. Clinical presentation of SCN is age-dependent, with kidney dysfunction slowly beginning to develop from childhood, progressing to chronic kidney disease and kidney failure during the third and fourth decades of life. This review explores the epidemiology, pathology, pathophysiology, clinical presentation, and management of SCN by focusing on the pediatric population. It also discusses the factors that can modify SCN susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ranque B, Menet A, Diop IB, Thiam MM, Diallo D, Diop S, Diagne I, Sanogo I, Kingue S, Chelo D, Wamba G, Diarra M, Anzouan JB, N’Guetta R, Diakite CO, Traore Y, Legueun G, Deme-Ly I, BelingaS Boidy K, Kamara I, Tharaux PL, Jouven X (2014) Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional study. Lancet Haematol 1:e64–e73

    Article  PubMed  Google Scholar 

  2. Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW, Dewi M, Temperley WH, Williams TN, Weatherall DJ, Hay SI (2013) Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet 381:142–151

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene- Frempong K, Krishnamurti L, Smith WR, Panepinto JA, Weatherall DJ, Costa FF, Vichinsky EP (2018) Sickle cell disease. Nat Rev Dis Prim 4:1–22

    Google Scholar 

  4. Taylor C, Kasztan M, Tao B, Pollock JS, Pollock DM (2019) Combined hydroxyurea and ETA receptor blockade reduces renal injury in the humanized sickle cell mouse. Acta Physiol 225:e13178

  5. Vichinsky E (2017) Chronic organ failure in adult sickle cell disease. Hematology 2017:435–439

    Article  PubMed  PubMed Central  Google Scholar 

  6. Andong AM, Ngouadjeu EDT, Bekolo CE, Verla VS, Nebongo D, Mboue-Djieka Y, Choukem SP (2017) Chronic complications and quality of life of patients living with sickle cell disease and receiving care in three hospitals in Cameroon: a cross-sectional study. BMC Hematol 17:7

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sharpe CC, Thein SL (2014) How I treat renal complications in sickle cell disease. Blood 123:3720–3726

    Article  CAS  PubMed  Google Scholar 

  8. Mammen C, Bissonnette ML, Matsell DG (2017) Acute kidney injury in children with sickle cell disease—compounding a chronic problem. Pediatr Nephrol 32:1287–1291

    Article  PubMed  Google Scholar 

  9. Adewoyin AS (2015) Management of sickle cell disease: a review for physician education in Nigeria (sub-Saharan Africa). Anemia 2015:791498

    Article  PubMed  PubMed Central  Google Scholar 

  10. Allison AC (1954) Protection afforded by sickle-cell trait against subtertian malarial infection. Br Med J 1:290–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Luzzatto L (2012) Sickle cell anaemia and malaria. Mediterr J Hematol Infect Dis 4:e2012065

    Article  PubMed  PubMed Central  Google Scholar 

  12. Modell B, Darlison M (2008) Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 86:480–487

    Article  PubMed  PubMed Central  Google Scholar 

  13. Saborio P, Scheinman JI (1999) Sickle cell nephropathy. J Am Soc Nephrol 10:187–192

    Article  CAS  PubMed  Google Scholar 

  14. Olaniran KO, Eneanya D, Nigwekar SU (2019) Sickle cell nephropathy in the pediatric population. Blood Purif 47:205–213

    Article  CAS  PubMed  Google Scholar 

  15. Wesson DE (2002) The initiation and progression of sickle cell nephropathy. Kidney Int 61:2277–2286

    Article  PubMed  Google Scholar 

  16. Brewin J, Tewari S, Hannemann A, Al Balushi H, Sharpe C, Gibson JS, Rees DC (2017) Early markers of sickle nephropathy in children with sickle cell anemia are associated with red cell cation transport activity. HemaSphere 1:e2

  17. Zahr RS, Yee ME, Weaver J, Twombley K, Matar RB, Aviles D, Sreedharan R, Rheault MN, Malatesta-Muncher R, Stone H, Srivastava T, Kapur G, Baddi P, Volovelsky O, Pelletier J, Gbadegesin R, Seeherunvong W, Patel HP, Greenbaum LA (2019) Kidney biopsy findings in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol 34:1435–1445

    Article  PubMed  Google Scholar 

  18. Nath KA, Katusic ZS (2012) Vasculature and kidney complications in sickle cell disease. J Am Soc Nephrol 23:781–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sharpe CC, Thein SL (2011) Sickle cell nephropathy - a practical approach. Br J Haematol 155:287–297

    Article  CAS  PubMed  Google Scholar 

  20. Becker AM (2011) Sickle cell nephropathy: challenging the conventional wisdom. Pediatr Nephrol 26:2099–2109

    Article  PubMed  Google Scholar 

  21. Van Avondt K, Nur E, Zeerleder S (2019) Mechanisms of haemolysis-induced kidney injury. Nat Rev Nephrol 15:671–692

    Article  PubMed  CAS  Google Scholar 

  22. Eshbach ML, Kaur A, Rbaibi Y, Tejero J, Weisz OA (2017) Hemoglobin inhibits albumin uptake by proximal tubule cells: Implications for sickle cell disease. Am J Phys Cell Physiol 312:C733–C740

    Article  Google Scholar 

  23. Rubio-Navarro A, Sanchez-Niño MD, Guerrero-Hue M, García-Caballero C, Gutiérrez E, Yuste C, Sevillano Á, Praga M, Egea J, Román E, Cannata P, Ortega R, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Ortiz A, Egido J, Moreno JA (2018) Podocytes are new cellular targets of haemoglobin-mediated renal damage. J Pathol 244:296–310

    Article  CAS  PubMed  Google Scholar 

  24. Inusa BPD, Mariachiara L, Giovanni P, Ataga KI (2018) Sickle cell nephropathy: current understanding of the presentation, diagnostic and therapeutic challenges. In: Hematology- Latest Research and Clinical Advances. pp 156–185

  25. Ataga KI, Derebail VK, Caughey M, Elsherif L, Shen JH, Jones SK, Maitra P, Pollock DM, Cai J, Archer DR, Hinderliter AL (2016) Albuminuria is associated with endothelial dysfunction and elevated plasma endothelin-1 in sickle cell anemia. PLoS One 11:e0162652

  26. Saraf SL, Zhang X, Shah B, Kanias T, Gudehithlu KP, Kittles R, Machado RF, Arruda JAL, Gladwin MT, Singh AK, Gordeuk VR (2015) Genetic variants and cell-free hemoglobin processing in sickle cell nephropathy. Haematologica 100:1275–1284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sundd P, Gladwin MT, Novelli EM (2019) Pathophysiology of sickle cell disease. Annu Rev Pathol Mech Dis 14:263–292

    Article  CAS  Google Scholar 

  28. Nath KA, Hebbel RP (2015) Sickle cell disease: renal manifestations and mechanisms. Nat Rev Nephrol 11:161–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nath KA, Belcher JD, Nath MC, Grande JP, Croatt AJ, Ackerman AW, Katusic ZS, Vercellotti GM (2018) Role of TLR4 signaling in the nephrotoxicity of heme and heme proteins. Am J Physiol Ren Physiol 314:F906–F914

    Article  CAS  Google Scholar 

  30. Belcher JD, Chen C, Nguyen J, Milbauer L, Abdulla F, Alayash AI, Smith A, Nath KA, Hebbel RP, Vercellotti GM (2014) Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood 123:377–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ghosh S, Adisa OA, Chappa P, Tan F, Jackson KA, Archer DR, Ofori-Acquah SF (2013) Extracellular hemin crisis triggers acute chest syndrome in sickle mice. J Clin Invest 123:4809–4820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Alleyne GA (1975) The kidney in sickle cell anemia. Kidney Int 7:371–379

    Article  CAS  PubMed  Google Scholar 

  33. Da Silva Junior GB, Libório AB, De Francesco DE (2011) New insights on pathophysiology, clinical manifestations, diagnosis, and treatment of sickle cell nephropathy. Ann Hematol 90:1371–1379

    Article  Google Scholar 

  34. Statius Van Eps LW, Schouten H, Ter Haar Romeny-Wachter CC, La Porte-Wijsman LW (1970) The relation between age and renal concentrating capacity in sickle cell disease and hemoglobin C disease. Clin Chim Acta 27:501–511

    Article  CAS  PubMed  Google Scholar 

  35. Scheinman J (1994) Sickle cell nephrology. In: Holliday M, Barratt T, Avner E (eds) Pediatric Nephrology. Williams & Wilkins, Baltimore, pp 908–914

    Google Scholar 

  36. Raj VMS, Freundlich M, Hamideh D, Alvarez O, Seeherunvong W, Abitbol C, Katsoufis C, Chandar J, Ruiz P, Zilleruelo G (2014) Abnormalities in renal tubular phosphate handling in children with sickle cell disease. Pediatr Blood Cancer 61:2267–2270

    Article  CAS  PubMed  Google Scholar 

  37. Marsenic O, Couloures KG, Wiley JM (2008) Proteinuria in children with sickle cell disease. Nephrol Dial Transplant 23:715–720

    Article  CAS  PubMed  Google Scholar 

  38. Feltran LDS, Carvalhaes JTDA, Sesso R (2002) Renal complications of sickle cell disease: managing for optimal outcomes. Pediatr Drugs 4:29–36

    Article  Google Scholar 

  39. Hariri E, Mansour A, El Alam A, Daaboul Y, Korjian S, Aoun Bahous S (2018) Sickle cell nephropathy: an update on pathophysiology, diagnosis, and treatment. Int Urol Nephrol 50:1075–1083

    Article  CAS  PubMed  Google Scholar 

  40. Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW (2011) Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet 377:1663–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Aloni MN, Ngiyulu RM, Ekulu PM, Mbutiwi FIN, Makulo JR, Gini-Ehungu JL, Nseka NM, Lepira FB (2017) Glomerular hyperfiltration is strongly correlated with age in Congolese children with sickle cell anaemia. Acta Paediatr Int J Paediatr 106:819–824

    Article  CAS  Google Scholar 

  42. Aloni MN, Mabidi JLL, Ngiyulu RM, Ekulu PM, Mbutiwi FI, Makulo JR, Sumaili EK, Gini-Ehungu JL, Nsibu CN, Nseka NM, Lepira FB (2017) Prevalence and determinants of microalbuminuria in children suffering from sickle cell anemia in steady state. Clin Kidney J 10:479–486

    Article  PubMed  PubMed Central  Google Scholar 

  43. Bernstein J, Whitten C (1960) A histologic appraisal of the kidney in sickle cell anemia. Arch Pathol 70:407–418

    CAS  PubMed  Google Scholar 

  44. Bhathena DB, Sondheimer JH (1991) The glomerulopathy of homozygous sickle hemoglobin (SS) disease: morphology and pathogenesis. J Am Soc Nephrol 1:1241–1252

    Article  CAS  PubMed  Google Scholar 

  45. Van Eps LWS, Schouten H, La Porte-Wijsman LW, Struyker Boudier AM (1967) The influence of red blood cell transfusions on the hyposthenuria and renal hemodynamics of sickle cell anemia. Clin Chim Acta 17:449–461

    Article  Google Scholar 

  46. Dharnidharka VR, Dabbagh S, Atiyeh B, Simpson P, Sarnaik S (1998) Prevalence of microalbuminuria in children with sickle cell disease. Pediatr Nephrol 12:475–478

    Article  CAS  PubMed  Google Scholar 

  47. Guasch A, Cua M, Mitch WE (1996) Early detection and the course of glomerular injury in patients with sickle cell anemia. Kidney Int 49:786–791

    Article  CAS  PubMed  Google Scholar 

  48. McBurney PG, Hanevold CD, Hernandez CM, Waller JL, McKie KM (2002) Risk factors for microalbuminuria in children with sickle cell anemia. J Pediatr Hematol Oncol 24:473–477

    Article  PubMed  Google Scholar 

  49. Guasch A, Cua M, You W, Mitch WE (1997) Sickle cell anemia causes a distinct pattern of glomerular dysfunction. Kidney Int 51:826–833

    Article  CAS  PubMed  Google Scholar 

  50. Day TG, Drasar ER, Fulford T, Sharpe CC, Thein SL (2012) Association between hemolysis and albuminuria in adults with sickle cell anemia. Haematologica 97:201–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Drawz P, Ayyappan S, Nouraie M, Saraf S, Gordeuk V, Hostetter T, Gladwin MT, Little J, (, (2016) Kidney disease among patients with sickle cell disease, hemoglobin SS and SC. Clin J Am Soc Nephrol 11:207–215

    Article  CAS  PubMed  Google Scholar 

  52. Bakir AA, Hathiwala SC, Ainis H, Hryhorczuk DO, Rhee HL, Levy PS, Dunear G (1987) Prognosis of the nephrotic syndrome in sickle glomerulopathy. Am J Nephrol 7:110–115

    Article  CAS  PubMed  Google Scholar 

  53. Powars DR, Elliott-Mills DD, Chan L, Niland J, Hiti AL, Opas LM, Johnson C (1991) Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality. Ann Intern Med 115:614–620

    Article  CAS  PubMed  Google Scholar 

  54. Bodas P, Huang A, O’Riordan MA, Sedor JR, Dell KM (2013) The prevalence of hypertension and abnormal kidney function in children with sickle cell disease -a cross sectional review. BMC Nephrol 14:2–7

    Article  Google Scholar 

  55. Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C (2005) Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore) 84:363–376

    Article  Google Scholar 

  56. Burdmann EA, Jha V (2017) Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents. Kidney Int 91:1033–1046

    Article  PubMed  Google Scholar 

  57. Van Wolfswinkel ME, Koopmans LC, Hesselink DA, Hoorn EJ, Koelewijn R, Van Hellemond JJ, Van Genderen PJJ (2016) Neutrophil gelatinase-associated lipocalin (NGAL) predicts the occurrence of malaria-induced acute kidney injury. Malar J 15:464

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Amoura A, Moktefi A, Halfon M, Karras A, Rafat C, Gibier JB, Gleeson PJ, Servais A, Argy N, Maillé P, Belenfant X, Gueutin V, Delpierre A, Tricot L, El Karoui K, Jourde-Chiche N, Houze S, Sahali D, Audard V (2020) Malaria, collapsing glomerulopathy, and focal and segmental glomerulosclerosis. Clin J Am Soc Nephrol 15:964–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ouma BJ, Ssenkusu JM, Shabani E, Datta D, Opoka RO, Idro R, Bangirana P, Park G, Joloba ML, Kain KC, John CC, Conroy AL (2020) Endothelial activation, acute kidney injury, and cognitive impairment in pediatric severe malaria. Crit Care Med 48:e734–e743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Adeloye A, Luzzatto L, Edington GM (1971) Severe malarial infection in a patient with sickle-cell anaemia. Br Med J 2:445–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Oniyangi O, Omari AA (2019) Malaria chemoprophylaxis in sickle cell disease. Cochrane Database Syst Rev 2019. https://doi.org/10.1002/14651858.CD003489.pub2

  62. Tewari S, Brousse V, Piel FB, Menzel S, Rees DC (2015) Environmental determinants of severity in sickle cell disease. Haematologica 100:1108–1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Power-Hays A, Li S, Mensah A, Sobota A (2020) Universal screening for social determinants of health in pediatric sickle cell disease: a quality-improvement initiative. Pediatr Blood Cancer 67:e28006

    PubMed  Google Scholar 

  64. World health organisation. Social determinants of health. https://www.who.int/health-topics/socialdeterminants-of-health. Accessed 27 March 2021

  65. Raphael JL (2020) Addressing social determinants of health in sickle cell disease: the role of Medicaid policy. Pediatr Blood Cancer 67:e28202

    Article  PubMed  Google Scholar 

  66. Naik RP, Derebail VK (2017) The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait. Expert Rev Hematol 10:1087–1094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Colombatti R, Maschietto N, Varotto E, Grison A, Grazzina N, Meneghello L, Teso S, Carli M, Milanesi O, Sainati L (2010) Pulmonary hypertension in sickle cell disease children under 10 years of age. Br J Haematol 150:601–609

    Article  CAS  PubMed  Google Scholar 

  68. Aygun B, Mortier NA, Smeltzer MP, Hankins JS, Ware RE (2011) Glomerular hyperfiltration and albuminuria in children with sickle cell anemia. Pediatr Nephrol 26:1285–1290

    Article  PubMed  PubMed Central  Google Scholar 

  69. Geard A, Pule GD, Chetcha Chemegni B, Ngo Bitoungui VJ, Kengne AP, Chimusa ER, Wonkam A (2017) Clinical and genetic predictors of renal dysfunctions in sickle cell anaemia in Cameroon. Br J Haematol 178:629–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Strumph K, Hafeman M, Ranabothu S, Gomes W, Benitez S, Kaskel F, Manwani D, Mahgerefteh J (2021) Nocturnal hypertension associated with stroke and silent cerebral infarcts in children with sickle cell disease. Pediatr Blood Cancer 68:e28883

  71. Moodalbail DG, Falkner B, Keith SW, Mathias RS, Araya CE, Zaritsky JJ, Stuart MJ (2018) Ambulatory hypertension in a pediatric cohort of sickle cell disease. J Am Soc Hypertens 12:542–550

    Article  PubMed  PubMed Central  Google Scholar 

  72. Shatat IF, Jakson SM, Blue AE, Johnson MA, Orak JK, Kalpatthi R (2013) Masked hypertension is prevalent in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol 28:115–120

    Article  PubMed  Google Scholar 

  73. Becker AM, Goldberg JH, Henson M, Ahn C, Tong L, Baum M, Buchanan GR (2014) Blood pressure abnormalities in children with sickle cell anemia. Pediatr Blood Cancer 61:518–522

    Article  PubMed  Google Scholar 

  74. Asnani MR, Fraser RA, Reid ME (2011) Higher rates of hemolysis are not associated with albuminuria in Jamaicans with sickle cell disease. PLoS One 6:e18863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Haymann JP, Stankovic K, Levy P, Avellino V, Tharaux PL, Letavernier E, Grateau G, Baud L, Girot R, Lionnet F (2010) Glomerular hyperfiltration in adult sickle cell anemia: a frequent hemolysis associated feature. Clin J Am Soc Nephrol 5:756–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP (1994) Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 330:1639–1644

    Article  CAS  PubMed  Google Scholar 

  77. Guasch A, Navarrete J, Nass K, Zayas CF (2006) Glomerular involvement in adults with sickle cell hemoglobinopathies: prevalence and clinical correlates of progressive renal failure. J Am Soc Nephrol 17:2228–2235

    Article  CAS  PubMed  Google Scholar 

  78. Ballas SK (2001) Effect of α-globin genotype on the pathophysiology of sickle cell disease. Pediatr Pathol Mol Med 20:277–286

    Google Scholar 

  79. Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M (2003) Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. J Am Med Assoc 289:1645–1651

    Article  CAS  Google Scholar 

  80. Toole JFO, Schilling W, Kunze D, Madhavan SM, Konieczkowski M, Gu Y, Luo L, Wu Z, Bruggeman LA, Sedor JR (2018) ApoL1 overexpression drives variant-independent cytotoxicity. J Am Soc Nephrol 29:869–879

    Article  Google Scholar 

  81. Ekulu PM, Nkoy AB, Betukumesu DK, Aloni MN, Makulo JRR, Sumaili EK, Mafuta EM, Elmonem MA, Arcolino FO, Kitetele FN, Lepira FB, van den Heuvel LP, Levtchenko EN (2019) APOL1 risk genotypes are associated with early kidney damage in children in sub-Saharan Africa. Kidney Int Rep 4:930–938

    Article  PubMed  PubMed Central  Google Scholar 

  82. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329:841–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, Friedman D, Briggs W, Dart R, Korbet S, Mokrzycki MH, Kimmel PL, Limou S, Ahuja TS, Berns JS, Fryc J, Simon EE, Smith MC, Trachtman H, Michel DM, Schelling JR, Vlahov D, Pollak M, Winkler CA (2011) APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 22:2129–2137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Ekulu PM, Nkoy AB, Adebayo OC, Kazadi OK, Aloni MN, Arcolino FO, Ngiyulu RM, Gini JLE, Lepira FB, Van den Heuvel LP, Levtchenko EN (2021) A focus on the association of Apol1 with kidney disease in children. Pediatr Nephrol 36:777–788

    Article  PubMed  Google Scholar 

  85. Kormann R, Jannot AS, Narjoz C, Ribeil JA, Manceau S, Delville M, Joste V, Prié D, Pouchot J, Thervet E, Courbebaisse M, Arlet JB (2017) Roles of APOL1 G1 and G2 variants in sickle cell disease patients: kidney is the main target. Br J Haematol 179:326–335

    Article  CAS  Google Scholar 

  86. Madhavan SM, O’Toole JF, Konieczkowski M, Ganesan S, Bruggeman LA, Sedor JR (2011) APOL1 localization in normal kidney and nondiabetic kidney disease. J Am Soc Nephrol 22:2119–2128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ma L, Shelness GS, Snipes JA, Murea M, Antinozzi PA, Cheng D, Saleem MA, Satchell SC, Banas B, Mathieson PW, Kretzler M, Hemal AK, Rudel LL, Petrovic S, Weckerle A, Pollak MR, Ross MD, Parks JS, Freedman BI (2015) Localization of APOL1 protein and mRNA in the human kidney: nondiseased tissue, primary cells, and immortalized cell lines. J Am Soc Nephrol 26:339–348

    Article  PubMed  CAS  Google Scholar 

  88. Uzureau S, Lecordier L, Uzureau P, Hennig D, Graversen JH, Homblé F, Mfutu PE, Oliveira Arcolino F, Ramos AR, La Rovere RM, Luyten T, Vermeersch M, Tebabi P, Dieu M, Cuypers B, Deborggraeve S, Rabant M, Legendre C, Moestrup SK, Levtchenko E, Bultynck G, Erneux C, Pérez-Morga D, Pays E (2020) APOL1 C-terminal variants may trigger kidney disease through interference with APOL3 control of actomyosin. Cell Rep 30:3821-3836.e13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lever JM, Boddu R, George JF, Agarwal A (2016) Heme oxygenase-1 in kidney health and disease. Antioxid Redox Signal 25:165–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Anderson S, Meyer TW, Rennke HG, Brenner BM (1985) Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 76:612–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Falk RJ, Scheinman J, Phillips G, Orringer E, Johnson A, Jennette JC (1992) Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme. N Engl J Med 326:910–915

    Article  CAS  PubMed  Google Scholar 

  92. Fitzhugh CD, Wigfall DR, Ware RE (2005) Enalapril and hydroxyurea therapy for children with sickle nephropathy. Pediatr Blood Cancer 45:982–985

    Article  PubMed  Google Scholar 

  93. Aoki RY, Saad STO (1995) Enalapril reduces the albuminuria of patients with sickle cell disease. Am J Med 98:432–435

    Article  CAS  PubMed  Google Scholar 

  94. McKie KT, Hanevold CD, Hernandez C, Waller JL, Ortiz L, McKie KM (2007) Prevalence, prevention, and treatment of microalbuminuria and proteinuria in children with sickle cell disease. J Pediatr Hematol Oncol 29:140–144

    Article  CAS  PubMed  Google Scholar 

  95. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR (1995) Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 332:1317–1322

    Article  CAS  PubMed  Google Scholar 

  96. Alvarez O, Montane B, Lopez G, Wilkinson J, Miller T (2006) Early blood transfusions protect against microalbuminuria in children with sickle cell disease. Pediatr Blood Cancer 47:71–76

    Article  PubMed  Google Scholar 

  97. De Jong PE, Van Eps LWS (1985) Sickle cell nephropathy: new insights into its pathophysiology. Kidney Int 27:711–717

    Article  PubMed  Google Scholar 

  98. Becton LJ, Kalpatthi RV, Rackoff E, Disco D, Orak JK, Jackson SM, Shatat IF (2010) Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease. Pediatr Nephrol 25:1505–1511

    Article  PubMed  Google Scholar 

  99. Warady BA, Sullivan EK (1998) Renal transplantation in children with sickle cell disease: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant 2:130–133

    CAS  PubMed  Google Scholar 

Download references

Funding

O.C.A. is supported by fundamental research grant of Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO) (grant number 11A5621N). E.N.L is supported by clinical investigator grant of FWO (grant number 1801110N).

Author information

Authors and Affiliations

  1. Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium

    Oyindamola C. Adebayo, Lambertus P. Van den Heuvel & Elena N. Levtchenko

  2. Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Leuven, Belgium

    Oyindamola C. Adebayo & Veerle Labarque

  3. Department of Pediatric Nephrology, Radboud University Medical Centre, Nijmegen, Netherlands

    Lambertus P. Van den Heuvel

  4. Pediatric Nephrology and Hypertension Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria

    Wasiu A. Olowu

  5. Department of Pediatric Nephrology, University Hospital Leuven, Herestraat 49, Bus 817, 3000, Leuven, Belgium

    Elena N. Levtchenko

  6. Department of Pediatric Hematology, University Hospital Leuven, Leuven, Belgium

    Veerle Labarque

Authors
  1. Oyindamola C. Adebayo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lambertus P. Van den Heuvel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wasiu A. Olowu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena N. Levtchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Veerle Labarque
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

O.C.A., L.P.H., W.A.O., E.N.L., and V.L. searched the literature and wrote the manuscript.

Corresponding author

Correspondence to Elena N. Levtchenko.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adebayo, O.C., Van den Heuvel, L.P., Olowu, W.A. et al. Sickle cell nephropathy: insights into the pediatric population. Pediatr Nephrol 37, 1231–1243 (2022). https://doi.org/10.1007/s00467-021-05126-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-021-05126-4

Keywords

Search

Navigation