What causes metabolic acidosis in Chronic Kidney Disease (CKD)?

From the Guidelines

Metabolic acidosis in Chronic Kidney Disease (CKD) is primarily caused by a combination of factors, including the kidneys' inability to excrete acid, decreased production of bicarbonate, and reduced ammonia production and excretion, with dietary patterns, such as high animal protein intake and low fruit and vegetable consumption, playing a significant role in the development of metabolic acidosis, as evidenced by the study published in the American Journal of Kidney Diseases in 2017 1. The kidneys' inability to excrete acid and maintain acid-base balance is a key factor in the development of metabolic acidosis in CKD patients. As kidney function declines, several mechanisms contribute to this acid accumulation, including:

• The kidneys' loss of capacity to excrete daily acid loads generated from protein metabolism, leading to hydrogen ion retention
• Decreased production of bicarbonate, which normally neutralizes acid in the body
• The kidneys becoming less efficient at reabsorbing filtered bicarbonate in the proximal tubules
• Reduced ammonia production and excretion, which further impairs acid elimination Dietary patterns, such as high animal protein intake and low fruit and vegetable consumption, can also contribute to the development of metabolic acidosis, as they lead to an imbalance between nonvolatile acids and the alkali needed to buffer these acids, resulting in a chronic low-grade metabolic acidosis that worsens with age as kidney function declines, as noted in the study published in the American Journal of Kidney Diseases in 2017 1. The severity of metabolic acidosis typically correlates with the stage of CKD, becoming more pronounced as glomerular filtration rate decreases. Some key points to consider in the management of metabolic acidosis in CKD patients include:
• The use of pharmacological treatment, such as sodium bicarbonate, to prevent the development of acidosis, as recommended in the KDIGO 2024 clinical practice guideline for the evaluation and management of CKD 1
• The importance of monitoring treatment for metabolic acidosis 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 noted in the KDIGO 2024 clinical practice guideline for the evaluation and management of CKD 1
• The potential benefits of dietary modifications, such as limiting animal protein intake and increasing fruits and vegetables, in reducing acid load and mitigating acidosis, as evidenced by the study published in the American Journal of Kidney Diseases in 2017 1
• The need for individualized treatment approaches, taking into account the patient's specific needs and circumstances, as noted in the KDOQI US commentary on the KDIGO 2024 clinical practice guideline for the evaluation and management of CKD 1

From the Research

Causes of Metabolic Acidosis in CKD

• Impaired ammonia excretion 2
• Reduced tubular bicarbonate reabsorption 2
• Insufficient renal bicarbonate production in relation to the amount of acids synthesized by the body and ingested with food 2
• Diminishing ability of the kidneys to maintain acid-base homeostasis, resulting in acid accumulation 3

Pathophysiology of Metabolic Acidosis in CKD

• The kidneys play an important role in regulating the acid-base balance, and metabolic acidosis is common in CKD patients 4
• Metabolic acidosis can lead to poor outcomes, such as bone demineralization, muscle mass loss, and worsening of renal function 4
• The degree of acidosis approximately correlates with the severity of renal failure and is usually more severe at a lower glomerular filtration rate (GFR) 5

Clinical Characteristics of Metabolic Acidosis in CKD

• Metabolic acidosis is noted in the majority of patients with CKD when GFR decreases to less than 20% to 25% of normal 5
• Acidosis is generally mild to moderate in degree, with plasma bicarbonate concentrations ranging from 12 to 22 mEq/L (mmol/L) 5
• Metabolic acidosis can be of the high-anion-gap variety, although anion gap can be normal or only moderately increased even with stage 4 to 5 CKD 5

Adverse Consequences of Metabolic Acidosis in CKD

• Muscle wasting 5, 6
• Bone disease 5, 6
• Impaired growth 5
• Abnormalities in growth hormone and thyroid hormone secretion 5
• Impaired insulin sensitivity 5
• Progression of renal failure 5, 2, 6
• Exacerbation of beta 2-microglobulin accumulation 5
• Hyperkalemia 6