How do systemic infections affect kidney function?

From the Guidelines

Systemic infections can significantly impair kidney function through multiple mechanisms, including the release of inflammatory mediators, hypotension, septic shock, direct damage from pathogens, and nephrotoxic medications, leading to acute kidney injury and potentially chronic kidney disease. When the body experiences a widespread infection, inflammatory mediators like cytokines and endotoxins are released, causing renal blood vessels to constrict and reducing blood flow to the kidneys. This decreased perfusion can lead to acute kidney injury, as defined by an increase in creatinine by 0.3 mg/dL within 48 hours or an increase in serum creatinine to 1.5 times baseline (within prior 7 days) or urine volume 0.5 mL/kg/hr for 6 hours 1. Additionally, infections often cause hypotension or septic shock, further compromising renal blood flow. The kidneys may also suffer direct damage from pathogens that reach them through the bloodstream, with bacteria like E. coli, Staphylococcus, and Streptococcus being common culprits. Certain medications used to treat infections, particularly aminoglycoside antibiotics and some antifungals, can be nephrotoxic and worsen kidney damage, as suggested by the KDIGO clinical practice guideline for acute kidney injury 1. Severe infections can trigger disseminated intravascular coagulation, forming small blood clots that block renal blood vessels. The body's immune response to infection can sometimes cause immune complex deposition in kidney tissues, leading to glomerulonephritis. Patients with systemic infections may also experience dehydration from fever, vomiting, or diarrhea, further stressing kidney function. Early detection and treatment of the underlying infection, along with supportive care to maintain adequate hydration and blood pressure, are essential to protect kidney function during systemic infections, as emphasized by the COVID-19 and acute kidney injury guidelines 1. It is also important to consider the potential risks and benefits of treatment options, including the use of vasopressors, fluids, and medications, in patients with systemic infections and kidney disease, as discussed in the EASL recommendations on treatment of hepatitis C 1. In patients with severe renal impairment or those on hemodialysis, treatment of HCV infection can be considered, but requires careful monitoring and dose adjustments, as recommended by the EASL guidelines 1. Overall, the management of systemic infections and kidney disease requires a comprehensive approach that takes into account the underlying causes of kidney injury, the potential risks and benefits of treatment options, and the need for supportive care to maintain adequate hydration and blood pressure.

From the FDA Drug Label

Nephrotoxicity Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Vancomycin should be used with caution in patients with renal insufficiency because the risk of toxicity is appreciably increased by high, prolonged blood concentrations.

Systemic Infections and Kidney Function: Systemic infections can hurt kidneys by increasing the risk of acute kidney injury (AKI). The risk of AKI increases with higher systemic exposure to certain substances, such as vancomycin.

• Key Factors:
  • Systemic exposure/serum levels
  • Underlying renal impairment
  • Co-morbidities that predispose to renal impairment
  • Concomitant therapy with a drug known to be nephrotoxic It is essential to monitor renal function in all patients, especially those with underlying renal impairment or receiving concomitant therapy with a nephrotoxic drug 2.

From the Research

Systemic Infections and Kidney Function

Systemic infections can significantly affect kidney function, leading to acute kidney injury (AKI) in some cases. The relationship between systemic infections and kidney function is complex, involving various mechanisms and pathways.

Mechanisms of Kidney Damage

• Sepsis, a systemic infection, can cause AKI by inducing inflammation, microvascular abnormalities, and tubular stress in the kidneys 3.
• The pathogenesis of septic AKI is complex, but emerging evidence suggests that functional defects, rather than structural damage, may occur in the first 48 hours of sepsis 3.
• Renal medullary hypoxia due to redistribution of intra-renal perfusion is a critical mediator of septic AKI 3.

Risk Factors and Outcomes

• Sepsis-associated AKI contributes to the morbidity and mortality of sepsis, with a growing body of knowledge illuminating clinical risk factors, pathobiology, response to treatment, and elements of renal recovery 4.
• Bactericidal antibiotics can temporarily increase inflammation and worsen AKI in experimental sepsis, but may also lead to faster resolution of inflammation and AKI 5.
• The incidence of antibiotic-induced AKI is significant, with aminoglycosides, amphotericin B, vancomycin, and beta-lactam antibiotics being common causes 6.
• Elevated baseline levels of inflammatory and endothelial cell activation biomarkers, such as E-selectin and albumin-to-creatinine ratio, are associated with an increased risk of AKI after sepsis 7.

Clinical Implications

• Vasopressor drugs, such as norepinephrine, remain the cornerstone of therapy for maintaining blood pressure and organ perfusion in septic AKI, but may have limited effectiveness in some cases 3.
• Alternative therapies, such as vasopressin, angiotensin II, and α2-adrenergic receptor agonists, may be feasible adjuncts for catecholamine-resistant vasodilatory shock 3.
• Early recognition and diagnosis of AKI, as well as prompt treatment, are crucial for improving outcomes in patients with systemic infections 4.