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Sickle cell disease and the kidney

Abstract

The renal features of sickle cell disease (SCD) include some of the most common reasons for referral to nephrologists, such as hematuria, proteinuria, tubular disturbances and chronic kidney disease. Therapy of these conditions requires specialized knowledge of their distinct pathogenic mechanisms. Painless hematuria is usually benign—unless massive—and can be treated with hydration alone if renal medullary carcinoma has been ruled out. Tubular functional defects, which tend to reduce urinary concentrating capacity, generally require no specific treatment. Proteinuria might indicate the development of chronic sickle cell nephropathy, which can be treated effectively. Measurement of glomerular filtration rate in SCD is problematic, which makes identification and monitoring of chronic kidney disease difficult in patients with SCD. Although managing and predicting the outcomes of chronic kidney disease in the SCD setting is challenging, affected individuals do benefit from transplantation. This Review summarizes the presentation, processes, pathology, modifiers, diagnosis and treatment of the renal effects of SCD.

Key Points

  • Hematuria in sickle cell disease (SCD) or sickle trait can be benign and usually requires only conservative management and an awareness of more-serious potential diagnoses such as renal medullary carcinoma

  • The principal tubule disorder in SCD is defective urinary concentrating capacity, but this complication should not generate serious problems unless there is injudicious use of fluids, NSAIDs or antihypertensive medications, or renal insufficiency

  • Chronic sickle cell nephropathy is a progressive form of focal segmental glomerulosclerosis that seems to begin with hyperperfusion and microalbuminuria and is probably amenable to measures to prevent its progression

  • Transplantation is a good option for patients with advanced sickle cell nephropathy, although the outcomes are not as favorable as for other types of end-stage renal disease

  • The measurement and monitoring of glomerular filtration rate, which is generally elevated in SCD, can be difficult and should be made easier by the use of more refined methods that can correctly detect changes in this parameter

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Figure 1: Ultrasonographic and urographic renal findings of an 18-year-old patient with sickle cell disease, abdominal pain and hematuria.

References

  1. Osegbe DN (1990) Haematuria and sickle cell disease: a report of 12 cases and review of the literature. Trop Geogr Med 42: 22–27

    CAS  PubMed  Google Scholar 

  2. Oksenhendler E et al. (1984) Recurrent hematuria in 4 white patients with sickle cell trait. J Urol 132: 1201–1203

    Article  CAS  PubMed  Google Scholar 

  3. Pandya KK et al. (1976) Renal papillary necrosis in sickle cell hemoglobinopathies. J Urol 115: 497–501

    Article  CAS  PubMed  Google Scholar 

  4. Odita JC et al. (1983) Urographic changes in homozygous sickle cell disease. Diagn Imaging 52: 259–263

    CAS  PubMed  Google Scholar 

  5. van Eps S and de Jong PE (1988) Sickle cell disease. In Diseases of the Kidney, 2561–2681 (Eds Schrier RW and Gottschalk CW) Boston: Little, Brown and Company

    Google Scholar 

  6. Davidson R and Wilcox CS (1991) Diagnostic usefulness of renal scanning after angiotensin converting enzyme inhibitors. Hypertension 18: 299–303

    Article  CAS  PubMed  Google Scholar 

  7. Burry A et al. (1977) Analgesic nephropathy and the renal concentrating mechanism. Pathol Annu 12: 1–31

    PubMed  Google Scholar 

  8. Sabatini S (1989) Pathophysiologic mechanisms of abnormal collecting duct function. Semin Nephrol 9: 179–202

    CAS  PubMed  Google Scholar 

  9. Keeler R and Wilson N (1989) Natriuretic response to hypervolemia is absent in rats with papillary necrosis. Am J Physiol 257: R422–R426

    CAS  PubMed  Google Scholar 

  10. Chauhan PM et al. (1983) Pathology of sickle cell disorders. Pathol Annu 18: 253–276

    PubMed  Google Scholar 

  11. Kersting U et al. (1994) Evidence for an acid pH in rat renal inner medulla: paired measurements with liquid ion-exchange microelectrodes on collecting ducts and vasa recta. Pflugers Arch 426: 354–356

    Article  CAS  PubMed  Google Scholar 

  12. Avery RA et al. (1996) Renal medullary carcinoma: clinical and therapeutic aspects of a newly described tumor. Cancer 78: 128–132

    Article  CAS  PubMed  Google Scholar 

  13. Schultz PK et al. (1991) Hyperechoic renal medullary pyramids in infants and children. Radiology 181: 163–167

    Article  Google Scholar 

  14. Walker TM and Serjeant GR (1995) Increased renal reflectivity in sickle cell disease: prevalence and characteristics. Clin Radiol 50: 566–569

    Article  CAS  PubMed  Google Scholar 

  15. Braden GL et al. (1985) Demeclocycline-induced natriuresis and renal insufficiency: in vivo . Am J Kidney Dis 5: 270–277

    Article  CAS  PubMed  Google Scholar 

  16. McCall IW et al. (1978) Urographic findings in homozygous sickle cell disease. Radiology 126: 99–104

    Article  CAS  PubMed  Google Scholar 

  17. Mapp E et al. (1987) Uroradiological manifestations of S-hemoglobinopathy. Semin Roentgenol 22: 186–194

    Article  CAS  PubMed  Google Scholar 

  18. Lang EK et al. (2004) Multiphasic helical CT diagnosis of early medullary and papillary necrosis. J Endourol 18: 49–56

    Article  PubMed  Google Scholar 

  19. Brawley OW et al. (2008) National Institutes of Health consensus development conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med 148: 932–938

    Article  PubMed  Google Scholar 

  20. Iyamu EW et al. (2001) Hydroxyurea-induced oxidative damage of normal and sickle cell hemoglobins in vitro: amelioration by radical scavengers. J Clin Lab Anal 15: 1–7

    Article  CAS  PubMed  Google Scholar 

  21. Grindel JM et al. (2002) Distribution, metabolism, and excretion of a novel surface-active agent, purified poloxamer 188, in rats, dogs, and humans. J Pharm Sci 91: 1936–1947

    Article  CAS  PubMed  Google Scholar 

  22. Devereux S and Knowles SM (1985) Rhabdomyolysis and acute renal failure in sickle cell anaemia. Br Med J (Clin Res Ed) 290: 1707

    Article  CAS  Google Scholar 

  23. Beutler E (1992) Erythrocyte disorders: anemias related to abnormal globulin. In Hematology, 613–626 (Eds Williams WJ et al.) New York: McGraw-Hill

    Google Scholar 

  24. Weatherall DJ et al. (2001) The hemoglobinopathies. In The Metabolic and Molecular Bases of Inherited Disease, 4571–4626 (Eds Scriver CR et al.) New York: McGraw-Hill

    Google Scholar 

  25. de Jong PE and Statius van Eps LW (1985) Sickle cell nephropathy: new insights into its pathophysiology. Kidney Int 27: 711–717

    Article  CAS  PubMed  Google Scholar 

  26. Allon M (1990) Renal abnormalities in sickle cell disease. Arch Intern Med 150: 501–504

    Article  CAS  PubMed  Google Scholar 

  27. Allon M et al. (1988) Effects of nonsteroidal antiinflammatory drugs on renal function in sickle cell anemia. Kidney Int 34: 500–506

    Article  CAS  PubMed  Google Scholar 

  28. DeFronzo RA et al. (1979) Impaired renal tubular potassium secretion in sickle cell disease. Ann Intern Med 90: 310–316

    Article  CAS  PubMed  Google Scholar 

  29. Herrera J et al. (2002) Impaired creatinine secretion after an intravenous creatinine load is an early characteristic of the nephropathy of sickle cell anaemia. Nephrol Dial Transplant 17: 602–607

    Article  CAS  PubMed  Google Scholar 

  30. Morgan AG et al. (1984) Glomerular function and hyperuricaemia in sickle cell disease. J Clin Pathol 37: 1046–1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. de Jong PE et al. (1983) The influence of indomethacin on renal acidification in normal subjects and in patients with sickle cell anemia. Clin Nephrol 19: 259–264

    CAS  PubMed  Google Scholar 

  32. Buckalew VM and Someren A (1974) Renal manifestations of sickle cell disease. Nephron 133: 660–669

    Google Scholar 

  33. Bakir AA et al. (1987) Prognosis of the nephrotic syndrome in sickle glomerulopathy: a retrospective study. Am J Nephrol 7: 110–115

    Article  CAS  PubMed  Google Scholar 

  34. Powars DR et al. (2005) Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore) 84: 363–376

    Article  Google Scholar 

  35. Guasch A et al. (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 

  36. Sklar AH et al. (1990) A population study of renal function in sickle cell anemia. Int J Artif Organs 13: 231–236

    Article  CAS  PubMed  Google Scholar 

  37. Falk RJ et al. (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 

  38. Guasch A et al. (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 

  39. Alvarez O et al. (2008) Short-term follow-up of patients with sickle cell disease and albuminuria. Pediatr Blood Cancer 50: 1236–1239

    Article  PubMed  Google Scholar 

  40. Thompson J et al. (2007) Albuminuria and renal function in homozygous sickle cell disease: observations from a cohort study. Arch Intern Med 167: 701–708

    Article  CAS  PubMed  Google Scholar 

  41. Yoshida Y et al. (1989) Glomerular hemodynamic changes vs hypertrophy in experimental glomerular sclerosis. Kidney Int 35: 654–660

    Article  CAS  PubMed  Google Scholar 

  42. Bhathena DB and 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 

  43. Jennette JC et al. (1987) Glomerulomegaly and focal segmental glomerulosclerosis associated with obesity and sleep-apnea syndrome. Am J Kidney Dis 10: 470–472

    Article  CAS  PubMed  Google Scholar 

  44. Nyberg E et al. (1994) Glomerular volume and renal function in children with different types of the nephrotic syndrome. Pediatr Nephrol 8: 285–289

    Article  CAS  PubMed  Google Scholar 

  45. Spear G (1960) Glomerular alterations in cyanotic congenital heart disease. Nephron 106: 347–367

    CAS  Google Scholar 

  46. Olson JL et al. (1982) Altered glomerular permselectivity and progressive sclerosis following extreme ablation of renal mass. Kidney Int 22: 112–126

    Article  CAS  PubMed  Google Scholar 

  47. Foucan L et al. (1998) A randomized trial of captopril for microalbuminuria in normotensive adults with sickle cell anemia. Am J Med 104: 339–342

    Article  CAS  PubMed  Google Scholar 

  48. Woolf AS and Fine LG (1991) Do glomerular hemodynamic adaptations influence the progression of human renal disease? Pediatr Nephrol 5: 88–93

    Article  CAS  PubMed  Google Scholar 

  49. Doi T et al. (1990) Glomerular lesions in mice transgenic for growth hormone and insulinlike growth factor-I: I: relationship between increased glomerular size and mesangial sclerosis. Am J Pathol 137: 541–552

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Lande IM et al. (1986) Sickle-cell nephropathy: MR imaging. Radiology 158: 379–383

    Article  CAS  PubMed  Google Scholar 

  51. Guasch A et al. (1999) Evidence that microdeletions in the alpha globin gene protect against the development of sickle cell glomerulopathy in humans. J Am Soc Nephrol 10: 1014–1019

    Article  CAS  PubMed  Google Scholar 

  52. Walser M (1990) Progression of chronic renal failure in man. Kidney Int 37: 1195–1210

    Article  CAS  PubMed  Google Scholar 

  53. Collins AJ et al. (2007) Excerpts from the United States Renal Data System 1996 annual data report. Am J Kidney Dis 49 (Suppl 1): S1–S296

    Google Scholar 

  54. Voskaridou E et al. (2006) markers of renal dysfunction in patients with sickle cell/beta-thalassemia. Kidney Int 69: 2037–2042

    Article  CAS  PubMed  Google Scholar 

  55. Alvarez O et al. (2006) Serum cystatin C levels in children with sickle cell disease. Pediatr Nephrol 21: 533–537

    Article  PubMed  Google Scholar 

  56. Schwartz GJ et al. (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58: 259–263

    Article  CAS  PubMed  Google Scholar 

  57. Cockcroft DW and Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41

    Article  CAS  PubMed  Google Scholar 

  58. Filler G and Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18: 981–985

    Article  PubMed  Google Scholar 

  59. Datta V et al. (2003) Microalbuminuria as a predictor of early glomerular injury in children with sickle cell disease. Indian J Pediatr 70: 307–309

    Article  PubMed  Google Scholar 

  60. Kattamis A et al. (2004) Clinical response and adverse events in young patients with sickle cell disease treated with hydroxyurea. Pediatr Hematol Oncol 21: 335–342

    Article  CAS  PubMed  Google Scholar 

  61. Tomson CR et al. (1992) Effect of recombinant human erythropoietin on erythropoiesis in homozygous sickle-cell anaemia and renal failure. Nephrol Dial Transplant 7: 817–821

    Article  CAS  PubMed  Google Scholar 

  62. Rodgers GP et al. (1993) Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. N Engl J Med 328: 73–80

    Article  CAS  PubMed  Google Scholar 

  63. Levasseur DN et al. (2003) Correction of a mouse model of sickle cell disease: lentiviral/antisickling beta-globin gene transduction of unmobilized, purified hematopoietic stem cells. Blood 102: 4312–4319

    Article  CAS  PubMed  Google Scholar 

  64. Ojo AO et al. (1999) Renal transplantation in end-stage sickle cell nephropathy. Transplantation 67: 291–295

    Article  CAS  PubMed  Google Scholar 

  65. Bleyer AJ et al. (2001) Relationship between underlying renal disease and renal transplantation outcome. Am J Kidney Dis 37: 1152–1161

    Article  CAS  PubMed  Google Scholar 

  66. Scheinman JI (2004) Sickle cell nephropathy. In Pediatric Nephrology, 917–930 (Eds Avner ED et al.) Philadelphia: Lippincott Williams & Wilkins

    Google Scholar 

  67. Spector D et al. (1978) Painful crises following renal transplantation in sickle cell anemia. Am J Med 64: 835–839

    Article  CAS  PubMed  Google Scholar 

  68. Chatterjee SN (1987) National study in natural history of renal allografts in sickle cell disease or trait: a second report. Transplant Proc 19 (Suppl 2): S33–S35

    Google Scholar 

  69. Donnelly PK et al. (1988) Renal transplantation in sickle cell disease. Lancet 2: 229

    Article  CAS  PubMed  Google Scholar 

  70. Miner DJ et al. (1987) Recurrent sickle cell nephropathy in a transplanted kidney. Am J Kidney Dis 10: 306–313

    Article  CAS  PubMed  Google Scholar 

  71. Smith-Whitley K et al. (2004) Epidemiology of human parvovirus B19 in children with sickle cell disease. Blood 103: 422–427

    Article  CAS  PubMed  Google Scholar 

  72. Johnson CS and Giorgio AJ (1981) Arterial blood pressure in adults with sickle cell disease. Arch Intern Med 141: 891–893

    Article  CAS  PubMed  Google Scholar 

  73. Sklar AH et al. (1990) Acute renal failure in sickle cell anemia. Int J Artif Organs 13: 347–351

    Article  CAS  PubMed  Google Scholar 

  74. Simckes AM et al. (1999) Ketorolac-induced irreversible renal failure in sickle cell disease: a case report. Pediatr Nephrol 13: 63–67

    Article  CAS  PubMed  Google Scholar 

  75. Koppes GM et al. (1977) Exertion-induced rhabdomyolysis with acute renal failure and disseminated intravascular coagulation in sickle cell trait. Am J Med 63: 313–317

    Article  CAS  PubMed  Google Scholar 

  76. Sty JR et al. (1980) Abnormal Tc-99m-methylene diphosphonate accumulation in the kidneys of children with sickle cell disease. Clin Nucl Med 5: 445–447

    Article  CAS  PubMed  Google Scholar 

  77. Swartz MA et al. (2002) Renal medullary carcinoma: clinical, pathologic, immunohistochemical, and genetic analysis with pathogenetic implications. Urology 60: 1083–1089

    Article  PubMed  Google Scholar 

  78. McCredie M et al. (1986) Phenacetin and papillary necrosis: independent risk factors for renal pelvic cancer. Kidney Int 30: 81–84

    Article  CAS  PubMed  Google Scholar 

  79. Hakimi AA et al. (2007) Renal medullary carcinoma: the Bronx experience. Urology 70: 878–882

    Article  PubMed  Google Scholar 

  80. Merched AJ et al. (2008) Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J 22: 3595–3606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. de Jong PE et al. (1978) The role of prostaglandins and renin in sickle-cell nephropathy: a hypothesis. Neth J Med 21: 67–72

    CAS  PubMed  Google Scholar 

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The author has served on an independent renal safety board for Novartis.

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Scheinman, J. Sickle cell disease and the kidney. Nat Rev Nephrol 5, 78–88 (2009). https://doi.org/10.1038/ncpneph1008

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