From the Guidelines
High anion gap metabolic acidosis in CKD stage 2 is primarily caused by the kidney's reduced ability to excrete acid, coupled with a dietary pattern of high animal protein intake and low fruit and vegetable consumption, leading to an imbalance between nonvolatile acids and available alkali. The main mechanism involves decreased ammonium excretion and reduced bicarbonate reabsorption, which leads to acid accumulation in the blood, as noted in studies examining the effects of diet on kidney function 1. As kidney function declines, even modestly in CKD stage 2, the body retains more hydrogen ions and fails to adequately filter out acid-producing compounds like phosphates and sulfates from protein metabolism. This causes an increase in unmeasured anions, creating the high anion gap. Other contributing factors may include uremic toxins that interfere with normal acid-base regulation, medication effects (particularly NSAIDs or certain antibiotics), and concurrent conditions like diabetic ketoacidosis or lactic acidosis that can worsen the acid-base imbalance.
Management typically involves treating the underlying kidney disease, limiting dietary acid load through reduced protein intake, and sometimes using oral bicarbonate supplementation to neutralize excess acid, with consideration for pharmacological treatment as suggested by recent guidelines 1. Regular monitoring of electrolytes and kidney function is essential as treatment is adjusted, ensuring that serum bicarbonate concentrations do not exceed the upper limit of normal and do not adversely affect blood pressure control, serum potassium, or fluid status 1. Key practice points include considering the use of pharmacological treatment with or without dietary intervention to prevent the development of acidosis, particularly when bicarbonate levels are less than 18 mmol/l in adults 1.
Some of the key benefits of managing metabolic acidosis in CKD include slowing the decline of kidney function, as demonstrated by studies showing that supplementation with sodium bicarbonate or increasing fruit and vegetable intake can significantly increase plasma bicarbonate levels and decrease net endogenous acid production 1. However, increasing fruit and vegetable intake is associated with additional benefits, such as significant decreases in systolic blood pressure and total-body weight, highlighting the importance of dietary modifications in the management of CKD and metabolic acidosis 1.
From the Research
Causes of High Anion Gap Metabolic Acidosis in CKD
- High anion gap metabolic acidosis can occur in patients with chronic kidney disease (CKD) due to the accumulation of endogenous acids that consume bicarbonate 2
- The causes of high anion gap metabolic acidosis include lactic acidosis, ketoacidosis, renal failure, and intoxication with certain substances such as ethylene glycol, methanol, and salicylate 2
- In CKD, high anion gap metabolic acidosis can develop due to the decreased ability of the kidneys to excrete acids and regenerate bicarbonate 3, 4
- The degree of acidosis in CKD approximately correlates with the severity of renal failure, and high anion gap metabolic acidosis is more common in advanced stages of CKD 3, 5
Association with CKD Progression
- High anion gap metabolic acidosis has been associated with an increased risk of kidney failure and mortality in patients with CKD 5
- A high anion gap has been shown to be a prognostic factor for the progression of CKD, and its association with kidney outcomes is independent of other factors such as serum bicarbonate concentration and glomerular filtration rate 4, 5
- The mechanisms by which high anion gap metabolic acidosis contributes to CKD progression are not fully understood, but may involve inflammation, oxidative stress, and endothelial dysfunction 6
Clinical Implications
- The diagnosis of high anion gap metabolic acidosis in CKD requires careful evaluation of blood pH, serum anion gap, and other acid-base parameters 4
- Treatment of high anion gap metabolic acidosis in CKD may involve administration of base, such as sodium bicarbonate, to normalize serum bicarbonate concentration and improve acid-base balance 3, 6
- However, the optimal treatment strategy for high anion gap metabolic acidosis in CKD is not well established, and further study is needed to determine the benefits and complications of base therapy in this population 3, 6