What are the newer drugs for treating acute kidney injury (AKI)?

Newer Drugs for Acute Kidney Injury

There are currently no newer pharmacological agents proven to treat or prevent acute kidney injury—management remains focused on supportive care, drug stewardship, and avoidance of nephrotoxic medications. 1, 2

Current State of Pharmacotherapy for AKI

The evidence is unequivocal: no specific drug therapies exist for the majority of AKI cases. 3 The KDIGO guidelines explicitly recommend against using several agents that were previously investigated:

• Do not use dopamine for AKI treatment 1
• Do not use diuretics for AKI treatment 1
• Do not use N-acetylcysteine (NAC) for AKI prevention, as demonstrated by the PRESERVE trial showing lack of efficacy 1
• Do not use recombinant human insulin-like growth factor 1 (IGF-1) 1
• Do not use synthetic colloids (particularly hydroxyethyl starches) as they increase AKI incidence and mortality in critically ill patients, especially those with sepsis 1

This telling observation highlights that mortality from AKI has remained unchanged for four decades despite numerous failed therapeutic trials. 3

What Actually Works: Drug Stewardship as "Treatment"

The most effective "newer" approach is comprehensive drug stewardship programs that prevent and mitigate drug-associated AKI. 1 This represents a paradigm shift from seeking novel therapeutics to optimizing medication management:

Core Drug Stewardship Strategies

• Include a clinical pharmacist for drug stewardship 1
• Identify patients at risk of AKI/AKD before prescribing nephrotoxic agents 1
• Avoid the "triple whammy" combination of renin-angiotensin system inhibitors, diuretics, and NSAIDs 1, 4
• Discontinue all nephrotoxic medications immediately when AKI develops, including ACE inhibitors, ARBs, NSAIDs, and diuretics 5, 4
• Assess the dynamic impact of AKI/AKD on drug pharmacokinetics/pharmacodynamics and adjust dosing accordingly 1
• Monitor patients receiving ≥3 nephrotoxic drugs daily, as this significantly increases AKI risk 1

Electronic Health Record Interventions

One single-center study demonstrated that using electronic health records to identify children exposed to 3 or more nephrotoxic drugs led to a sustained decrease in AKI incidence—this represents one of the few successful interventions. 1

Supportive Care: The Only "Treatment"

Since no targeted pharmacotherapies exist, management focuses on:

Fluid Management

• Use isotonic crystalloids (not colloids) for initial volume expansion in patients with or at risk for AKI 1, 5, 4
• Avoid 0.9% saline when possible—evidence continues to accumulate showing biochemical abnormalities and adverse outcomes compared with balanced crystalloids like lactated Ringer's 1
• Ensure adequate hydration and correction of renal perfusion to prevent and treat AKI 1
• Avoid goal-directed fluid therapy protocols in early septic shock, as large multicenter RCTs showed lack of benefits for survival and kidney outcomes 1

Hemodynamic Support

• Consider earlier use of vasopressors rather than excessive fluid administration for hypotension 1
• Maintain mean arterial pressure >65 mmHg to ensure renal perfusion 5

Contrast Media Management

Modern iodinated contrast agents carry far fewer risks than previously thought—significant kidney injury is unusual in patients with normal or mildly reduced baseline kidney function. 1 The PRESERVE trial definitively showed that:

• Sodium bicarbonate solutions do not prevent contrast-induced AKI 1
• Oral N-acetylcysteine does not prevent contrast-induced AKI 1
• Do not withhold i.v. contrast in life-threatening conditions where diagnostic information could have important therapeutic implications 1

Renal Replacement Therapy: Not a "Drug" But Critical

RRT is the only supportive measure for severe AKI with oligoanuria and fluid accumulation, though it is not a pharmacological intervention. 6, 7 Key considerations:

• Initiate RRT emergently for life-threatening complications: refractory hyperkalemia, volume overload, intractable acidosis, or uremic symptoms 1, 4
• Early initiation of RRT does not improve outcomes—studies have not consistently demonstrated benefit to early-start dialysis 2
• Reassess need for continued RRT daily 4

Critical Pitfalls to Avoid

• Failing to discontinue nephrotoxic medications during AKI is perhaps the most common and preventable error 5, 4
• Restarting ACE inhibitors/ARBs too early before kidney function stabilizes—wait at least 3 months after AKI to evaluate for resolution 5
• Using synthetic colloids in critically ill patients, which directly cause AKI 1
• Delaying RRT when clear indications exist, which increases mortality 4
• Inadequate follow-up after AKI episodes, which increases risk of progression to CKD 5

Future Directions

The KDIGO conference identified urgent need for advancement in understanding AKI pathophysiology and treatment. 1 Current research priorities include:

• Development of new biomarkers for early AKI detection (TIMP-2, IGFBP-7) 6
• Optimal timing, dose, and modality of RRT 4
• Role of sodium bicarbonate in AKI with metabolic acidosis 4
• Development of new classification systems describing renal effects of drugs 1

The sobering reality is that after decades of research, no "newer drugs" have emerged for AKI treatment—prevention through drug stewardship and supportive care remain the only evidence-based approaches. 1, 2, 3