International Urology and Nephrology

, Volume 48, Issue 8, pp 1291–1304 | Cite as

Hemophagocytic lymphohistiocytosis: an update for nephrologists

  • Edward J. FilipponeEmail author
  • John L. Farber
Nephrology - Review


Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by defective lytic capability of cytotoxic T lymphocytes and NK cells, which results in proliferation of benign hemophagocytic histiocytes. A cytokine storm ensues, and a severe systemic inflammatory response syndrome, multiorgan dysfunction syndrome, and death frequently follow. It may occur as a primary (inherited) form, or be acquired secondary to malignancy, infection, rheumatologic disease, or immunosuppression. Cardinal manifestations include fever, cytopenias, hepatosplenomegaly, and dysfunction of liver, kidney, CNS, and/or lung. Additional laboratory findings include marked hyperferritinemia, hypofibrinogenemia, hypertriglyceridemia, abnormal LFTs, coagulopathy, and hyponatremia. Nephrologists need to be aware of this syndrome owing to the frequent occurrence of acute kidney injury in these severely ill patients. Glomerulopathy and nephrotic syndrome may develop. Kidney transplant recipients are at increased risk of HLH due to immunosuppression, and most such cases are triggered by infection with over 50 % mortality. Effective treatment of HLH usually requires chemoimmunotherapy to acutely suppress inflammation, specific treatment of underlying infection or malignancy, and in certain cases hematopoietic stem cell transplantation. The pathogenesis, clinical manifestations, diagnosis, and treatment of HLH are discussed.


Hemophagocytic lymphohistiocytosis Macrophage activation syndrome Hemophagocytic syndrome Acute kidney injury Kidney transplantation Systemic inflammatory response syndrome 


Compliance with ethical standards

Conflict of interest

EJF: speaker’s bureau for Mallinckrodt Pharmaceuticals; JLF: none.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Division of Nephrology, Department of Medicine, Sydney Kimmel School of MedicineThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of Pathology, Sydney Kimmel School of MedicineThomas Jefferson UniversityPhiladelphiaUSA
  3. 3.PhiladelphiaUSA

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