What is the role of the kidneys in maintaining acid-base balance?

From the Guidelines

The kidneys play a crucial role in maintaining acid-base balance in the body, and in people with chronic kidney disease (CKD), consideration should be given to pharmacological treatment with or without dietary intervention to prevent the development of acidosis, as recommended by the KDIGO 2024 clinical practice guideline 1. The kidneys regulate blood pH by excreting excess acids or bases and reabsorbing or generating bicarbonate as needed. The proximal tubule reabsorbs about 80% of filtered bicarbonate, while the distal tubule and collecting duct secrete hydrogen ions and generate new bicarbonate. Some key points to consider in acid-base balance in the kidneys include:

• The kidneys excrete titratable acids (like phosphate) and ammonium, which allows for elimination of acid without depleting bicarbonate.
• When blood becomes too acidic (acidosis), the kidneys increase hydrogen ion secretion and bicarbonate reabsorption and generation.
• Conversely, in alkalosis, they reduce hydrogen secretion and bicarbonate reabsorption.
• This process is regulated by various hormones including aldosterone, which enhances hydrogen ion secretion, and angiotensin II, which stimulates bicarbonate reabsorption.
• Disorders affecting these mechanisms can lead to renal tubular acidosis, characterized by impaired acid excretion or bicarbonate reabsorption. It is also important to note that reducing net acid production (NEAP) through increased bicarbonate or a citric acid/sodium citrate solution supplementation can help reduce the rate of decline of residual kidney function in adults with CKD 3-5D, as recommended by the KDOQI clinical practice guideline for nutrition in CKD: 2020 update 1. In terms of specific recommendations, maintaining serum bicarbonate levels at 24-26 mmol/L is reasonable in adults with CKD 3-5D, according to the KDOQI clinical practice guideline for nutrition in CKD: 2020 update 1. However, the most recent and highest quality study, the KDIGO 2024 clinical practice guideline, recommends considering pharmacological treatment with or without dietary intervention to prevent the development of acidosis in people with CKD, with potential clinical implications, such as serum bicarbonate <18 mmol/l in adults 1.

From the Research

Acid-Base Balance in the Kidneys

• The kidneys play a crucial role in maintaining acid-base balance by reabsorbing bicarbonate and excreting titratable acids and ammonia into the urine 2.
• In chronic kidney disease (CKD), acid retention and metabolic acidosis occur due to declining kidney function, and the extent of acid retention depends on the degree of kidney impairment and dietary acid load 2.
• Acid-base disorders can lead to changes in mechanisms involved in acid-base balance maintenance and affect multiple other mechanisms, including inflammation and metabolism, which are tightly wired to it 3.

Mechanisms of Acid-Base Balance

• The kidneys regulate acid-base balance by reabsorbing bicarbonate filtered by the glomeruli and excreting titratable acids and ammonia into the urine 2.
• In CKD, acid transport processes in the surviving nephrons are augmented, but as disease progresses, ammonia excretion and the ability to reabsorb bicarbonate fall, whereas titratable acid excretion is preserved until kidney function is severely impaired 2.
• Urinary ammonia levels are used to gauge the renal response to acid loads and are best assessed by direct measurement of urinary ammonia levels rather than by indirect assessments 2.

Treatment of Metabolic Acidosis

• Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis in CKD, and it may even slow the progression of CKD 4, 5, 6.
• Studies have shown that sodium bicarbonate therapy can increase serum bicarbonate levels and improve kidney function, although the evidence is not consistent across all studies 4, 5, 6.
• The safety profile of sodium bicarbonate is generally favorable, with no significant association found with adverse outcomes such as death, prolonged hospitalization, gastrointestinal disorders, or worsening edema 5.
• Treatment of metabolic acidosis with sodium bicarbonate has been shown to delay progression of CKD and improve kidney and patient survival in some studies 6.