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Acid-Base Relationships in Hemodialysis (HD) Patients and Their Management

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1. Background: Why HD Patients Have Acid-Base Disturbances

• Loss of renal buffering capacity: The kidneys normally excrete ~50–100 mEq of non-volatile acid daily (from protein catabolism, dietary acid load). In ESRD, this capacity is almost entirely lost.
• Impaired ammoniagenesis: The tubular mechanism for NH₄⁺ excretion — the major route of net acid excretion — is abolished.
• Reduced bicarbonate regeneration: The collecting duct cannot regenerate HCO₃⁻ to replace that consumed in buffering.
• Intermittent dialysis: HD corrects acid-base status only during sessions (typically 3×/week), so acid accumulates inter-dialytically.

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2. The Dominant Disorder: Metabolic Acidosis

Characteristics

Pathophysiology

• Accumulation of sulfate, phosphate, hippurate, and other organic anions → high AG component
• Impaired H⁺ secretion → normal AG (hyperchloremic) component also present
• Mixed HAGMA + NAGMA is common
• Chronic acidosis activates bone buffering → calcium and phosphate released from bone → worsening renal osteodystrophy

Clinical Consequences of Persistent Acidosis (Kraut & Madias, Am J Kidney Dis 67:307, 2016)

• Accelerated protein catabolism and muscle wasting
• Bone disease (dissolution of bone mineral buffers)
• Impaired growth hormone / IGF-1 axis
• Worsening hyperkalemia (K⁺ shifts extracellularly with H⁺)
• Cardiovascular: decreased myocardial contractility, arrhythmia susceptibility
• Accelerated CKD progression (in residual renal function patients)
• Increased mortality in observational studies

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3. HD Dialysate and Acid-Base Correction

Bicarbonate Dialysate

• Standard dialysate HCO₃⁻: 35–40 mEq/L
• Correction occurs via diffusion gradient: dialysate HCO₃⁻ >> plasma HCO₃⁻
• A typical HD session raises serum HCO₃⁻ by 6–8 mEq/L

Post-Dialysis Overshoot

• After dialysis, there is typically a transient metabolic alkalosis (HCO₃⁻ may reach 26–30 mEq/L immediately post-session)
• This is expected and self-correcting as acid accumulates inter-dialytically
• Target: pre-dialysis HCO₃⁻ of 22–26 mEq/L (KDOQI/KDIGO recommendation)

Dialysate Prescription Adjustment

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4. KDIGO / KDOQI Management Targets

"A serum bicarbonate of <18 mmol/L in adults is desirable to avoid... correction of bicarbonate to the normal range has not been demonstrated to reduce the risk of kidney failure, but lower thresholds could be considered."

• Pre-dialysis serum HCO₃⁻: ≥ 22 mEq/L (most guidelines)
• Avoid persistent pre-dialysis HCO₃⁻ < 17–18 mEq/L
• Avoid chronic post-dialysis HCO₃⁻ > 27–28 mEq/L

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5. Additional Interventions: Oral Alkali Therapy

Per KDIGO (p. 107): "Licensed non-alkali oral interventions may be an alternative to oral sodium bicarbonate but have not been shown to have particular advantages."

• Each gram provides ~12 mEq of Na⁺ → can worsen hypertension and fluid overload
• Must be balanced against cardiovascular risk

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6. Other Acid-Base Disorders in HD Patients

Metabolic Alkalosis

• Causes: excess dialysate bicarbonate, prolonged vomiting, diuretic use (if residual urine output), nasogastric suction, post-dialysis overshoot
• Management: reduce dialysate HCO₃⁻; treat underlying cause; acetate-based bath historically used (now largely abandoned)

Respiratory Acidosis

• Common in HD patients with fluid overload causing pulmonary edema → hypoventilation
• Also in obese patients with obesity hypoventilation syndrome
• Management: optimize volume status; manage underlying lung/chest disease

Respiratory Alkalosis

• Causes: anxiety, pain, sepsis, early salicylate toxicity, hepatic encephalopathy
• Often compensatory in context of metabolic acidosis

Mixed Disorders

• HAGMA + respiratory alkalosis: common in septic dialysis patients
• HAGMA + NAGMA: typical of ESRD (combined organic acid accumulation + impaired H⁺ secretion)
• Metabolic alkalosis + metabolic acidosis: e.g., vomiting superimposed on uremic acidosis

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7. Special Considerations

Hyperkalemia and Acidosis

• Each 0.1 decrease in pH → ~0.5–0.7 mEq/L rise in serum K⁺ (transcellular shift)
• In HD patients, acidosis exacerbates life-threatening hyperkalemia
• Correcting acidosis is part of hyperkalemia management in ESRD

Bone Disease

• Chronic acidosis → increased osteoclast activity → calcium mobilization from bone
• Contributes to adynamic bone disease and secondary hyperparathyroidism
• Correcting acidosis may reduce PTH levels and slow bone loss

Residual Kidney Function

• Patients with residual diuresis may have better inter-dialytic HCO₃⁻ maintenance
• Loss of residual function (RRF) typically worsens acidosis

Frequent / Prolonged Dialysis

• Daily or nocturnal HD → better acid-base control, less inter-dialytic acidosis
• Pre-dialysis HCO₃⁻ tends to be higher and more stable

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8. Summary Algorithm

Pre-dialysis HCO₃⁻ measurement
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    < 18 mEq/L ───────────────────────> Intensify correction:
         |                               • ↑ Dialysate HCO₃⁻ (up to 40 mEq/L)
    18–22 mEq/L ──────────────────────> • Add oral NaHCO₃ (0.5–1 mEq/kg/day)
         |                               • Review dietary protein & acid load
    22–26 mEq/L ──────────────────────> Target achieved — maintain prescription
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    > 26 mEq/L ───────────────────────> Risk of alkalosis:
                                         • ↓ Dialysate HCO₃⁻
                                         • Review for vomiting, excess alkali intake

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Key Takeaways

1. Metabolic acidosis (mixed HAGMA + NAGMA) is the universal acid-base disturbance in HD patients, driven by daily acid accumulation from absent renal H⁺ excretion.
2. Bicarbonate dialysate is the primary correction mechanism; target pre-dialysis HCO₃⁻ of 22–26 mEq/L.
3. Oral sodium bicarbonate supplements dialysis correction when needed, with caution regarding sodium/volume load.
4. Post-dialysis alkalosis is expected and transient; persistent pre-dialysis alkalosis warrants reducing dialysate HCO₃⁻.
5. Chronic acidosis drives muscle catabolism, bone disease, and worsens hyperkalemia — making correction clinically important beyond biochemical targets.
6. KDIGO recommends avoiding serum HCO₃⁻ < 18 mEq/L; large RCTs are still needed to define precise correction targets for mortality benefit.