Does Heparin (Unfractionated Heparin) cause Acute Kidney Injury (AKI)?

From the Guidelines

Heparin can potentially cause acute kidney injury (AKI), though it is not among the most common causes, and the risk appears higher with unfractionated heparin compared to low molecular weight heparins. Heparin-induced AKI typically occurs through two main mechanisms. First, heparin can cause an immune-mediated condition called heparin-induced thrombocytopenia (HIT), which may lead to kidney damage through thrombosis in renal vessels. Second, some patients may develop heparin-associated hyperkalemia with aldosterone suppression, which can impact kidney function. According to a recent study 1, the use of low molecular weight heparin (LMWH) is preferred over unfractionated heparin (UFH) due to better bioavailability, fixed dosing, decreased risk of heparin-induced thrombocytopenia (HIT), and osteoporosis. However, LMWH can accumulate with renal impairment and has a longer half-life than UFH.

Some key points to consider when using heparin include:

• Monitoring kidney function and platelet counts in patients receiving heparin therapy, especially during the first 5-10 days of treatment when HIT typically develops 1
• Considering alternative anticoagulants if AKI is suspected while a patient is on heparin
• Evaluating for other potential causes of kidney injury
• Being aware that most cases of heparin-related kidney injury resolve with discontinuation of the medication
• Noting that patients with pre-existing kidney disease, advanced age, or those receiving high doses of heparin may be at increased risk of AKI, as suggested by a study on chronic kidney disease and risk management 1.

It is also important to recognize that AKI is diagnosed by a 50% or greater sustained increase in serum creatinine over a short period of time, which is also reflected as a rapid decrease in eGFR 1. Timely identification and treatment of AKI is crucial because AKI is associated with increased risks of progressive CKD and other poor health outcomes 1.

From the Research

Heparin and Acute Kidney Injury (AKI)

• The relationship between heparin and AKI is complex, with some studies suggesting that heparin may not directly cause AKI, but rather, its use is associated with a lower risk of bleeding events in patients with AKI 2.
• A study published in Frontiers in Pharmacology found that early heparin therapy was associated with decreased ICU mortality in patients with sepsis-associated AKI, particularly in females, patients over 60 years old, and those with AKI stage 3 3.
• Another study published in Research and Practice in Thrombosis and Haemostasis found that therapeutic-dose heparin was associated with a reduced incidence of severe AKI or death in non-critically ill patients hospitalized for COVID-19, with a high probability of superiority to reduce the composite of stage 3 AKI or death 4.
• However, a study published in the European Heart Journal: Acute Cardiovascular Care found that the risk of AKI was not significantly different between bivalirudin and unfractionated heparin groups in patients with acute coronary syndrome undergoing invasive management 5.
• The diagnosis and management of AKI involve determining the underlying cause, which can be categorized as prerenal, intrinsic renal, or postrenal, and implementing general management principles such as fluid resuscitation, treatment of volume overload, and discontinuation of nephrotoxic medications 6.

Key Findings

• Heparin may not directly cause AKI, but its use is associated with a lower risk of bleeding events in patients with AKI 2.
• Early heparin therapy may be beneficial in reducing ICU mortality in patients with sepsis-associated AKI, particularly in certain subgroups 3.
• Therapeutic-dose heparin may reduce the incidence of severe AKI or death in non-critically ill patients hospitalized for COVID-19 4.
• The risk of AKI was not significantly different between bivalirudin and unfractionated heparin groups in patients with acute coronary syndrome undergoing invasive management 5.

Study Limitations

• The studies had varying patient populations, study designs, and outcomes, which may limit the generalizability of the findings 2, 3, 4, 5.
• Further research is needed to fully understand the relationship between heparin and AKI, particularly in different patient populations and clinical settings 2, 3, 4, 5.