The kidney is the primary organ for excretion of uric acid. Patients with proximal tubular dysfunction have decreased excretion of uric acid and are more prone to gouty arthritis attacks. Depending on the pH and uric acid concentration, deposition can occur in the tubules, the interstitium, or the urinary tract. The more alkaline pH of the interstitium causes urate salt deposition, whereas the acidic environment of the tubules and urinary tract causes uric acid crystal deposition at high concentrations.
Three disorders are commonly seen: (1) uric acid nephrolithiasis, (2) acute uric acid nephropathy, and (3) chronic urate nephropathy. Kidney dysfunction with uric acid nephrolithiasis stems from obstructive physiology. Acute uric acid nephropathy presents with direct tubulointerstitial toxicity from uric acid crystals and distal tubule obstruction caused by precipitation of uric acid crystals. Chronic urate nephropathy is caused by deposition of urate crystals in the alkaline medium of the interstitium; this can lead to fibrosis and atrophy. Epidemiologically, hyperuricemia and gout have been associated with worse cardiovascular outcomes.
Treatment between gouty attacks involves avoidance of food and drugs causing hyperuricemia (see Chapter 20), aggressive hydration, and urate-lowering therapy (such as with allopurinol and febuxostat). The three disorders mentioned above are seen in both “overproducers” and “underexcretors” of uric acid. The latter situation may seem counterintuitive; however, these patients have acidic urine, which enables precipitation of relatively insoluble uric acid crystals. For those with uric acid nephrolithiasis, fluid intake should exceed 3 L/day, and use of a urinary alkalinizing agent can be considered. Patients with hyperuricemia who do not have a history of gout or uric acid nephrolithiasis have not been shown to benefit from urate-lowering therapy.
et al; CKD-FIX Study Investigators. Effects of allopurinol on the progression of chronic kidney disease. N Engl J Med. 2020;382:2504.
et al. Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the National Kidney Foundation. Am J Kidney Dis. 2018;71:851.