Metabolic Acidosis and Renal Damage

Pathophysiology

Prolonged acidosis can cause tubular atrophy and necrosis, particularly when combined with other risk factors, leading to direct tubular damage through increased acid load to the kidneys 1
Acidosis can cause bone demineralization, releasing calcium and phosphate that can precipitate in renal tissue and further damage renal structures and impair function 2
Oxalate crystals can precipitate in renal tubules during acidosis, inducing tubular damage and necrosis 1

Pre-existing conditions such as renal disease, hypovolemia, dehydration, and hypomagnesemia, as well as the use of nephrotoxic medications, can contribute to renal damage in the context of metabolic acidosis 1, 3
Certain drugs, such as corticosteroids, thiazides, and sympathomimetic agents, can contribute to ketoacidosis 4

Metabolic acidosis is defined as a blood pH below 7.35, corresponding to a hydrogen ion concentration greater than 45 nmol/L, as defined by the American Thoracic Society 5
The anion gap ([Na+] - ([Cl-] + [HCO3-])) is crucial in diagnosing metabolic acidosis, with a normal range of 8-12 mEq/L and elevated levels (> 12 mEq/L) indicating anion gap metabolic acidosis, as recommended by the American Society of Nephrology 6
The severity of metabolic acidosis can be classified based on the total CO2 level:

Total CO2 Level	Severity of Metabolic Acidosis
≥19 mmol/L	Mild
<19 mmol/L	Moderate to Severe [7, 8]

Initial laboratory testing should include arterial blood gases, complete metabolic panel, serum ketones, serum lactate, serum osmolality, and urinalysis, as recommended by the American College of Emergency Physicians 9

Fluid resuscitation with isotonic saline at 15-20 mL/kg/hr initially is recommended for all causes of metabolic acidosis, as suggested by the American College of Emergency Physicians 9, 4
Insulin therapy is recommended to correct ketoacidosis/ketosis, followed by the initiation of metformin while continuing subcutaneous insulin once acidosis resolves, as recommended by the American Diabetes Association 10
Bicarbonate therapy may be considered for severe acidosis (pH <7.2), with a dosing regimen of 1-2 mEq/kg sodium bicarbonate over 1 hour, but the European Society of Intensive Care Medicine recommends against using sodium bicarbonate to treat metabolic acidosis arising from tissue hypoperfusion 4, 11
Hemodialysis is recommended for severe acidosis, renal failure, or toxic alcohol levels ≥50 mg/dL, according to the Critical Care society 12

A protein intake of 0.8 g/kg body weight per day is recommended for non-dialysis CKD patients to slow disease progression, while high protein intake (>1.3 g/kg/day) should be avoided as it can accelerate kidney function decline, as recommended by the American Journal of Kidney Diseases 13
Restriction of dietary sodium (<2,300 mg/day) and individualization of dietary potassium are recommended for patients with renal disease, as suggested by the American Journal of Kidney Diseases 13
Lowering salt intake to <2g sodium per day is recommended by the American Journal of Transplantation 14
Increasing fruit and vegetable consumption can be an alternative source of alkali, and has been shown to be as effective as sodium bicarbonate in increasing plasma bicarbonate levels, with the added benefit of reducing systolic blood pressure and body weight, as suggested by the American Journal of Kidney Diseases 15

Serial monitoring of acid-base status and renal function is crucial, and resolution of the anion gap should parallel clinical improvement, as stated by the National Kidney Foundation
Serial arterial or venous blood gases should be performed to assess response to treatment, and regular monitoring of serum bicarbonate levels (monthly for chronic conditions) should be done to adjust bicarbonate dosage and maintain serum bicarbonate within normal range (22-29 mmol/L), as recommended by the American Journal of Kidney Diseases 7, 16
Clinical assessment should involve vital signs, mental status evaluation, signs of dehydration, and evidence of shock or tissue hypoperfusion, according to the American College of Critical Care Medicine 9, 17

Targeting BP ≤140/90 mmHg for patients with CKD and urine albumin <30 mg/24h, and BP <130/80 mmHg for those with CKD and urine albumin ≥30 mg/24h, is recommended by the American Journal of Transplantation 14
Considering ACE inhibitors or ARBs, especially with albuminuria, is suggested by the American Journal of Transplantation 14

Treatment for ethylene glycol poisoning includes fomepizole or ethanol and hemodialysis, as recommended by the Society of Critical Care Medicine 12
Correcting serum bicarbonate to ≥22 mmol/L with alkali replacement therapy, typically using potassium citrate, with a target serum bicarbonate level of ≥22 mmol/L, is recommended by the American Society of Nephrology 6
Oral calcium supplementation at mealtime can bind oxalate in the gut, reducing the risk of renal damage 1
Maintaining adequate hydration and high urinary flow can help prevent crystal formation 1
Avoiding excessive use of loop diuretics, which can cause renal hypoperfusion and worsen acidosis, is recommended 3