A process that may contribute to kidney damage in patients with sickle cell disease (SCD) was recently described in a special communication in Blood, written by Santosh L. Saraf, MD, from the University of Illinois at Chicago.1

In his communication, Dr Saraf explained that acute kidney injury can be a complication of vaso-occlusive episodes associated with SCD, and he discussed a related study also published in the same journal issue.1 The companion study examined heme-associated kidney injury with SCD and was conducted by Solomon F. Ofori-Acquah, PhD, from the University of Pittsburgh in Pennsylvania, and the University of Ghana in Accra, Ghana, and colleagues.2

Dr Saraf highlighted the importance of haptoglobin and hemopexin in scavenging free hemoglobin and heme, respectively, that can arise from intravascular hemolysis. Levels of both haptoglobin and hemopexin can become limited in SCD, which can result in an excess of free heme with the potential to cause kidney damage through a variety of mechanisms.1

In the study by Dr Ofori-Acquah and colleagues, a deficiency of hemopexin with SCD was accompanied by elevated alpha-1-microglobulin (A1M), and this pattern was associated with signs of hemolysis and acute kidney injury. In this study, in healthy mice, excess heme was directed to the liver, while in mice with SCD, excess heme traveled to the kidneys, which became damaged. In hemopexin-deficient mice with SCD, hemopexin that was given prior to a hemin challenge resulted in less evidence of kidney damage.2

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A1M is a protein that can traverse the glomerular filtration barrier, Dr Saraf explained. He also noted that in the study by Dr Ofori-Acquah and colleagues, A1M given just before a hemin infusion enhanced the negative impact on kidney function in hemopexin-deficient mice with SCD.1

The results obtained by Dr Ofori-Acquah and colleagues “strengthen the observation that kidney damage is mediated by intravascular hemolysis and provide novel insight that A1M may transport toxic cell-free heme to the kidneys in hemopexin-deficient states,” Dr Saraf wrote in his commentary. He also suggested that haptoglobin may be more impactful at limiting kidney damage than hemopexin is.1

References

  1. Saraf SL. Heme A1M’ed at the kidney in sickle cell disease. Blood. 2020;135(13):979-981.
  2. Ofori-Acquah SF, Hazra R, Orikogbo OO, et al; SickleGenAfrica Network. Hemopexin deficiency promotes acute kidney injury in sickle cell disease. Blood. 2020;135(13):1044-1048.