Capillary leak syndrome: etiologies, pathophysiology, and management

Kidney Int. 2017 Jul;92(1):37-46. doi: 10.1016/j.kint.2016.11.029. Epub 2017 Mar 17.


In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.

Keywords: acute kidney injury; capillary leak syndrome; capillary permeability; cytokines.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / epidemiology
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / therapy
  • Animals
  • Capillaries / physiopathology*
  • Capillary Leak Syndrome / diagnosis
  • Capillary Leak Syndrome / epidemiology
  • Capillary Leak Syndrome / physiopathology
  • Capillary Leak Syndrome / therapy*
  • Capillary Permeability*
  • Diagnosis, Differential
  • Fluid Therapy* / adverse effects
  • Hemodynamics
  • Humans
  • Plasma Substitutes / adverse effects
  • Plasma Substitutes / therapeutic use*
  • Pleural Effusion / epidemiology
  • Pleural Effusion / physiopathology
  • Pleural Effusion / therapy
  • Predictive Value of Tests
  • Risk Factors
  • Sepsis / complications
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Treatment Outcome


  • Plasma Substitutes
  • Sodium Potassium Chloride Symporter Inhibitors