Can renal failure cause lactic acidosis?

Can Renal Failure Cause Lactic Acidosis?

Yes, renal failure can cause lactic acidosis through impaired lactate clearance, particularly when combined with severe hepatic dysfunction or other metabolic stressors, though it is not the most common mechanism of lactic acidosis in isolation.

Mechanisms by Which Renal Failure Contributes to Lactic Acidosis

Primary Pathophysiology

• Renal failure impairs lactate clearance because the kidneys normally contribute to lactate metabolism and elimination, particularly when hepatic function is compromised 1
• The combination of acute renal failure (ARF) with severe hepatic failure creates a particularly high-risk scenario, with 90% of ARF patients who developed lactic acidosis also having severe hepatic failure 1
• Lactic acidosis results from two simultaneous mechanisms: lactate overproduction (tissue hypoxia) and lactate underutilization (severe liver and/or renal failure), with the latter mechanism playing a critical role in determining prognosis 1

Clinical Evidence and Severity

• In a study of 18 adults with ARF, 55% developed lactic acidosis with mortality reaching 80% in those with lactic acidosis versus 66.7% in ARF alone 1
• Patients with ARF and lactic acidosis demonstrated severely elevated lactate levels (76.7 ± 15.66 mg/dl), arterial pH of 7.20 ± 0.04, and bicarbonate levels of 10.6 ± 1.20 mEq/L 1
• Significant correlations exist between lactate levels and pH, bicarbonate, and anion gap, but not with BUN or creatinine alone, suggesting renal failure contributes but is not the sole determinant 1

Drug-Induced Lactic Acidosis in Renal Failure

Metformin as a Key Example

• Metformin accumulation in renal impairment is a major cause of lactic acidosis, as metformin is substantially excreted by the kidney and accumulation increases with severity of renal impairment 2
• The FDA states that metformin decreases liver uptake of lactate, increasing blood lactate levels, which further compounds the risk in patients with renal dysfunction 2
• One guideline notes an association between reduced kidney function (creatinine clearance <70 mL/min) and development of lactic acidosis in patients receiving NRTIs 3

Clinical Cases

• Multiple case reports document metformin-induced lactic acidosis precipitated by acute renal failure, with pH values as low as 6.71 and lactate levels reaching 24.4 mmol/L 4, 5
• These cases typically present with gastrointestinal symptoms, mental confusion, Kussmaul breathing, and hemodynamic instability 4, 5

Iatrogenic Considerations in Renal Failure

Lactate-Buffered Solutions

• Using lactate-buffered dialysis or hemofiltration fluids in patients with renal failure can worsen lactic acidosis rather than correct it 6, 7
• In patients at or near their threshold for lactate utilization, exogenous lactate loads during hemofiltration resulted in hyperlactataemia in all patients, with less than 40% showing expected improvements in acid-base status 6
• A positive correlation exists between increased arterial lactate and hydrogen ion concentrations (r = 0.52, p < 0.01) when lactate-buffered solutions are used 6

Treatment Implications

• Bicarbonate-buffered replacement fluids should be used instead of lactate-buffered solutions in patients with renal failure and lactic acidosis 8, 6, 7
• Continuous renal replacement therapy (CRRT) with bicarbonate-buffered fluids is recommended for severe acidosis with renal failure 8

Important Clinical Caveats

Risk Stratification

• The combination of renal failure with hepatic dysfunction creates the highest risk for lactic acidosis, as both organs contribute to lactate metabolism 1
• Renal failure alone is less likely to cause severe lactic acidosis unless combined with tissue hypoxia, shock, sepsis, or drug accumulation (particularly metformin) 2, 1

Monitoring Requirements

• In patients with renal impairment on metformin, assess eGFR at least annually, and more frequently in elderly patients or those at risk for renal deterioration 2
• Metformin is contraindicated when eGFR falls below 30 mL/min/1.73 m² 2

Prevention Strategies

• Avoid lactate-containing IV solutions and dialysate in patients with renal failure who have or are at risk for lactic acidosis 8, 6, 7
• Discontinue metformin immediately when acute renal failure develops or during acute illness that may affect kidney function 9, 2
• Monitor acid-base status regularly during renal replacement therapy to ensure adequate correction 8