When should Lactated Ringer's (LR) solution be used instead of Normal Saline (NS) in patients with Acute Kidney Injury (AKI)?

When to Use Lactated Ringer's Instead of Normal Saline in AKI

Lactated Ringer's (LR) should be used as the preferred first-line crystalloid for fluid resuscitation in most patients with AKI, with the critical exception of patients with severe traumatic brain injury or increased intracranial pressure, where normal saline (NS) is mandatory. 1, 2

Primary Recommendation for AKI

Use balanced crystalloids (LR) rather than NS for initial fluid resuscitation in AKI patients to reduce the risk of major adverse kidney events, hyperchloremic metabolic acidosis, and potentially mortality. 3, 1

• The KDIGO guidelines recommend isotonic crystalloids for volume expansion in patients at risk for or with established AKI, with emerging evidence favoring balanced solutions 3
• Large-scale evidence from the SMART trial (n=15,802 ICU patients) demonstrated that balanced crystalloids resulted in lower rates of major adverse kidney events (MAKE-30: death, doubling of creatinine, or need for renal replacement therapy) compared to NS 1
• The SALT trial showed lower 30-day in-hospital mortality and reduced incidence of renal replacement therapy with balanced crystalloids versus saline 1

Mechanism of Benefit in AKI

LR prevents hyperchloremic metabolic acidosis and reduces chloride-mediated renal vasoconstriction, which are key mechanisms of NS-induced kidney injury. 3, 1, 4

• NS contains supraphysiologic chloride (154 mmol/L vs. 108 mmol/L in LR), leading to hyperchloremic acidosis with large-volume administration 1, 4
• High chloride loads cause renal afferent arteriolar vasoconstriction, reducing glomerular filtration rate 3
• LR's balanced electrolyte composition more closely resembles plasma, avoiding these deleterious effects 1, 4

Absolute Contraindications to LR (Use NS Instead)

Avoid LR in patients with severe traumatic brain injury, increased intracranial pressure, or cerebral edema due to its hypotonic nature (osmolarity 273-277 mOsm/L vs. 308 mOsm/L for NS). 1, 2

• LR is hypotonic when measured by real osmolality and can worsen cerebral edema 2
• European guidelines specifically recommend NS as the isotonic crystalloid of choice for brain-injured patients 2
• This is the single most important exception to preferential LR use 1, 2

Avoid LR in crush syndrome or rhabdomyolysis with severe hyperkalemia due to its potassium content (4 mmol/L). 2

• Reperfusion of crushed limbs releases massive potassium loads 2
• The baseline potassium in LR poses additional risk in this specific scenario 2

Clinical Algorithm for Fluid Selection in AKI

Step 1: Assess for Absolute Contraindications

• If severe TBI or increased ICP present: Use NS exclusively 1, 2
• If crush syndrome with severe hyperkalemia (K+ >6.5 mmol/L): Use NS or potassium-free crystalloid 2

Step 2: For All Other AKI Patients

• Use LR as first-line fluid 3, 1
• This includes patients with:
  • Prerenal AKI 4
  • Sepsis-associated AKI 5, 6
  • Pre-existing chronic kidney disease 4
  • Mild-to-moderate hyperkalemia (K+ <6.5 mmol/L) 2

Step 3: Volume Considerations

• If using NS, limit to maximum 1-1.5 L to minimize hyperchloremic acidosis 1
• For larger volume requirements, switch to LR 3, 1

Evidence in Specific AKI Populations

Prerenal AKI with Pre-existing CKD

LR and NS show similar short-term kidney function recovery, but LR provides superior acid-base balance correction. 4

• A prospective study in prerenal AKI patients with CKD stage III-V showed no difference in kidney function improvement at discharge or 30 days 4
• LR demonstrated better anion gap improvement (Δanion-gap) and pH correction compared to NS 4
• Neither fluid increased dialysis requirements 4

Sepsis-Associated AKI

LR reduces blood transfusion requirements and total fluid volumes compared to NS in septic shock, with lower rates of hyperchloremia and hyperlactacidemia. 5, 6

• Septic shock patients receiving LR required less blood products on day 1 (606±273 mL vs. 782±357 mL) and lower total fluid volumes over 3 days 5
• LR reduced hyperchloremia incidence (13.2% vs. 25.0%, OR: 2.179) 5
• Benefits were greatest in patients with chronic pulmonary disease 6
• Patients with moderate-to-severe liver disease showed smaller benefits due to impaired lactate metabolism 6

Common Pitfalls and Caveats

Do not avoid LR solely based on mild hyperkalemia or existing renal dysfunction—the 4 mmol/L potassium content is physiologic and does not cause clinically significant hyperkalemia in most AKI patients. 1, 2

• Large randomized studies (n=30,000) showed comparable plasma potassium levels between NS and balanced solutions 2
• In renal transplant recipients (high hyperkalemia risk), NS actually resulted in higher potassium levels than LR 2
• Physiologically, fluids with potassium concentrations ≤ plasma concentration cannot create potassium excess 2

Monitor for lactate elevation when using LR in patients with severe liver disease—this reflects impaired lactate metabolism, not worsening shock. 6

• Serum lactate levels increase more with LR than NS (0.12 mg/dL/h difference), especially in chronic liver disease 6
• This does not indicate treatment failure but rather the lactate buffer being metabolized 6

Avoid excessive fluid administration regardless of crystalloid type—both LR and NS can cause volume overload and worsen AKI outcomes. 3

• Fluid administration should be guided by frequent hemodynamic reassessment 3
• Target tissue perfusion markers (lactate clearance, urine output, MAP) rather than fixed volumes 3

Hemorrhagic Shock Considerations

In hemorrhagic shock with AKI risk, balanced crystalloids (LR) are probably recommended over NS, though evidence is less robust than in other AKI settings. 3

• French guidelines suggest balanced crystalloids reduce mortality and adverse renal events in hemorrhagic shock (Grade 2+ recommendation) 3
• High-volume chloride-rich solutions (>5000 mL) are associated with increased mortality in observational studies 3
• However, no large RCTs have specifically studied crystalloid choice in hemorrhagic shock with median volumes typically <2000 mL 3