Factors That Increase Uric Acid in Hemodialysis Patients
Paradoxically, higher dialysis adequacy (Kt/V) is associated with increased serum uric acid levels in hemodialysis patients, and neither increasing dialysis duration nor adequacy effectively controls uric acid levels. 1
Key Factors Associated with Elevated Uric Acid
Nutritional Status and Body Composition
- Better nutritional status directly correlates with higher serum uric acid levels in maintenance hemodialysis patients 2, 3
- Higher albumin and creatinine levels (markers of better nutrition) positively correlate with elevated uric acid 2
- Increased body composition parameters, including lean tissue index and fat tissue index, associate with higher uric acid 4, 2
- Greater handgrip strength (r = 0.26; P < 0.001) correlates with elevated uric acid, reflecting better muscle mass and nutritional state 2
- Lower malnutrition-inflammation scores (indicating better nutrition) correlate with higher uric acid (r = -0.33; P < 0.001) 2
Dialysis-Related Factors
- Dialysis adequacy (Kt/V) shows a positive correlation with uric acid (R=0.43, P=0.029), meaning patients with higher Kt/V have higher plasma uric acid 1
- Dialysis duration does not significantly affect serum uric acid levels 1
- The hemodialysis procedure itself causes acute reductions in uric acid, but this does not reflect chronic control 5
- Uric acid clearance during hemodialysis is approximately 70-100 mL/min, with plasma levels falling by about 50% per 6-hour treatment, but this is temporary 6
Inflammatory Status
- Lower inflammatory markers (reduced interleukin-6 levels) correlate with higher uric acid (r = -0.13; P = 0.04) 2
- Reduced C-reactive protein levels associate with elevated uric acid 3
Metabolic and Dietary Factors
- Diuretic use can increase uric acid levels in the context of renal dysfunction 7
- Dietary purine intake influences uric acid production, though this is less controllable in dialysis patients 1
- Starvation or reducing diets paradoxically may increase uric acid 7
Clinical Context: Why This Matters
The relationship between uric acid and hemodialysis is counterintuitive compared to the general population. While high uric acid typically indicates cardiovascular risk in healthy individuals, in hemodialysis patients, higher uric acid reflects better nutritional status and associates with improved survival 4, 2, 3.
Survival Implications
- A U-shaped mortality pattern exists, with optimal uric acid around 6.5 mg/dL (387 μmol/L) 4
- For each 1 mg/dL increase in baseline uric acid, all-cause death hazard ratio is 0.55 (95% CI, 0.43-0.72) and cardiovascular death hazard ratio is 0.55 (95% CI, 0.35-0.80) 2
- Longitudinal increases in uric acid over time associate with multivariate adjusted all-cause mortality hazard ratio of 0.83 (95% CI, 0.74 to 0.95; P<0.01) 3
Common Pitfalls and Caveats
- Do not aggressively treat elevated uric acid in hemodialysis patients solely based on levels, as higher values may indicate better nutritional status rather than pathology 1, 2
- Recognize that increasing dialysis adequacy or duration will not effectively lower uric acid and may paradoxically increase it 1
- Understand that post-dialysis uric acid measurements show acute reductions but do not reflect chronic control 5
- The reciprocal relationship between uric acid and paraoxonase (PON1) activity (r² = 0.4, P < 0.001) suggests a protective antioxidant mechanism in hemodialysis patients 5
- Medical therapy, dietary modification, or lifestyle changes may be necessary if uric acid control is clinically indicated, rather than relying on dialysis intensification 1