Can hyperuricemia cause kidney damage?

From the Guidelines

Yes, uricemia can cause kidney damage, as high levels of uric acid in the blood can lead to the formation of crystals that deposit in the kidneys, causing inflammation and potentially chronic kidney disease. According to the 2017 study published in the Annals of the Rheumatic Diseases 1, a number of studies have demonstrated that both hyperuricaemia and gout are associated with chronic kidney disease (CKD). The study highlights that CKD appears to be a major risk factor for gout and, conversely, gout might cause renal dysfunction.

Key Points to Consider

• The prevalence of CKD (stage ≥2) in patients with SUA level ≥10 mg/dL and in patients with gout was 86% and 53%, respectively, as reported in the 2017 study 1.
• The task force agreed that identifying CKD in patients with gout was of major importance because of the therapeutic implications, and recommended that estimated glomerular filtration rate (eGFR) should be calculated at the time of diagnosis for CKD classification and monitored regularly in parallel with SUA measurement.
• The 2012 American College of Rheumatology guidelines for management of gout also support the association between hyperuricemia and kidney disease, stating that chronic interstitial nephropathy, mediated by monosodium urate monohydrate crystal deposition in the renal medulla, can occur in severe disease 1.

Treatment and Prevention

• Treatment typically involves medications that lower uric acid levels, such as allopurinol or febuxostat, which inhibit xanthine oxidase, the enzyme responsible for uric acid production.
• Maintaining adequate hydration and dietary modifications to reduce purine intake can also help manage uric acid levels.
• Early intervention is crucial, as prolonged hyperuricemia can lead to irreversible kidney damage, making regular monitoring of kidney function and uric acid levels essential for at-risk individuals.

From the FDA Drug Label

Some patients with pre-existing renal disease or poor urate clearance have shown a rise in BUN during administration of allopurinol tablets Renal failure in association with administration of allopurinol tablets has been observed among patients with hyperuricemia secondary to neoplastic diseases. Renal failure is also frequently associated with gouty nephropathy and rarely with hypersensitivity reactions associated with allopurinol tablets. Albuminuria has been observed among patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis Patients with decreased renal function require lower doses of allopurinol tablets than those with normal renal function.

Uricemia and Kidney Damage: Uricemia, or high levels of uric acid in the blood, can be associated with kidney damage, particularly in patients with pre-existing renal disease or poor urate clearance 2.

• Key Points:
  • Renal failure has been observed in patients with hyperuricemia secondary to neoplastic diseases.
  • Gouty nephropathy is frequently associated with renal failure.
  • Albuminuria has been observed in patients with clinical gout following chronic glomerulonephritis and chronic pyelonephritis.
  • Patients with decreased renal function require lower doses of allopurinol tablets. It is essential to carefully monitor patients with impaired renal function during the early stages of allopurinol administration and adjust the dosage accordingly to minimize the risk of kidney damage 2.

From the Research

Uricemia and Kidney Damage

• Uricemia, or high levels of uric acid in the blood, has been associated with an increased risk of kidney disease and cardiovascular events 3, 4, 5, 6.
• The kidneys play a major role in regulating serum uric acid levels, with approximately two-thirds of uric acid produced in humans being excreted by the kidneys 6.
• Hyperuricemia has been shown to predict kidney disease onset and progression, with various mechanisms implicated, including the handling of urate in the renal proximal tubule 6.

Treatment of Hyperuricemia

• Reducing hyperuricemia with low protein and low purine diets, as well as medications such as allopurinol and febuxostat, may help slow the progression of kidney disease 3, 4, 7.
• Febuxostat has been shown to be effective in lowering serum uric acid levels and delaying the progression of renal impairment in patients with chronic kidney disease and hyperuricemia 3, 7.
• The use of urate-lowering therapy (ULT) for nephroprotection in hyperuricemic patients with kidney disease is still a topic of debate, with some studies showing divergent outcomes 5.

Mechanisms of Kidney Damage

• High uric acid levels may play a causal role in kidney disease, although the exact mechanisms are not fully understood 4, 5.
• Theories on the possible multiple pathogenic mechanisms underlying hyperuricemia-related kidney damage include the role of uric acid in inflammation, oxidative stress, and endothelial dysfunction 4, 5.
• Further studies are needed to fully understand the relationship between hyperuricemia and kidney disease, and to determine the most effective treatments for reducing the risk of kidney damage 5, 6.