From the Guidelines
Uremia is a condition characterized by the accumulation of waste products in the blood due to kidney failure, and it commonly causes metabolic acidosis through several mechanisms, including the inability to excrete acid or reabsorb bicarbonate, leading to an acid-base imbalance, as supported by the most recent guideline evidence 1.
Mechanisms of Metabolic Acidosis in Uremia
When kidneys fail, they cannot adequately excrete acid or reabsorb bicarbonate, leading to an acid-base imbalance. Specifically, uremia causes metabolic acidosis because the kidneys can no longer effectively eliminate hydrogen ions produced during normal metabolism, and they fail to regenerate bicarbonate needed to buffer these acids. Additionally, the retention of phosphates and sulfates, which are acidic compounds normally cleared by functioning kidneys, further contributes to the acidic state.
Clinical Implications and Treatment
The body attempts to compensate through respiratory mechanisms (increased breathing rate to eliminate carbon dioxide) and by buffering with bone calcium, but these mechanisms are often insufficient in severe kidney failure. Patients with uremic acidosis typically present with symptoms like fatigue, nausea, and confusion, and may require treatment with oral sodium bicarbonate supplements or, in severe cases, intravenous sodium bicarbonate.
- The treatment goal is to increase bicarbonate levels toward but not greater than the normal range with sodium bicarbonate or other agents, as recommended by the KDOQI Work Group 1.
- Acidosis in adults should only be treated with pharmacologic agents when bicarbonate < 18 mmol/l or if there is a clear indication to do so, according to the most recent clinical practice guidelines 1.
- Dialysis is ultimately needed for patients with end-stage kidney disease to remove accumulated acids and restore acid-base balance.
Key Considerations
- Monitoring treatment for metabolic acidosis is crucial to ensure it does not result in serum bicarbonate concentrations exceeding the upper limit of normal and does not adversely affect BP control, serum potassium, or fluid status, as emphasized in the KDIGO 2024 clinical practice guideline 1.
- The threshold for aggressive intervention has been moved to <18 mmol/l from <22 mmol/l in the previous KDIGO guideline, highlighting the importance of timely and appropriate treatment 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Definition of Uremia
Uremia is a condition characterized by the accumulation of waste products, such as urea, in the blood due to kidney dysfunction or failure.
Relationship between Uremia and Metabolic Acidosis
- Metabolic acidosis is a common complication of chronic kidney disease (CKD) and uremia, resulting from the kidneys' inability to maintain acid-base homeostasis 2, 3.
- The diminishing ability of the kidneys to excrete acids leads to acid accumulation, causing various complications such as impairment in nutritional status, worsened uremic bone disease, and increased mortality 3.
- Metabolic acidosis can be diagnosed by evaluating blood pH and serum anion gap, in addition to serum bicarbonate levels 4.
Mechanisms of Metabolic Acidosis in Uremia
- The early stages of uremia may result in hyperchloremic metabolic acidosis, while the anion-gap form of metabolic acidosis occurs in advanced renal disease 5.
- The inability of the kidneys to keep pace with the metabolic acid load depletes extracellular fluid bicarbonate, leading to anion-gap acidosis 5.
- Metabolic acidosis can activate the catabolism of protein and amino acids in muscle, contributing to protein wasting and lean body mass loss in uremic patients 6.
Treatment and Management
- Oral bicarbonate supplementation and increased fruit and vegetable intake can help treat metabolic acidosis and slow the progression of CKD 2, 3.
- Veverimer, a non-absorbed, counterion-free, polymeric drug, is emerging as a potential treatment for metabolic acidosis, but further research is needed 2, 4.