Uric Acid Nephropathy/Gout
Shane M. Meehan, MBBCh
Key Facts
Terminology
Intrarenal precipitation of uric acid associated with hyperuricemia
Etiology/Pathogenesis
Decreased uric acid excretion (75-90%)
Overproduction of uric acid (10-25%)
Clinical Issues
Acute UAN: Acute oliguric or anuric renal failure
Chronic UAN: Chronic renal failure and hypertension
Macroscopic Features
Acute UAN: Medullary and papillary yellow radial striations
Chronic UAN: Medullary yellow flecks corresponding to tophi or microtophi
Uric acid stones
Microscopic Pathology
Acute UAN: Birefringent urate crystals in collecting ducts forming linear streaks, acute tubular injury
Chronic UAN: Medullary foreign body-type granulomas containing needle-like urate crystals or crystal clefts (= microtophus)
Top Differential Diagnoses
Acute tubular injury with crystal deposits: Indinavir, acyclovir, sulfadiazine, light chain proximal tubulopathy
Chronic nephropathy with granulomas: Cholesterol granulomas, oxalate nephropathy, indinavir or acyclovir nephropathy, sarcoidosis
 Gross photograph reveals a brown calculus with a rough surface in the renal pelvis. There is marked calyceal dilation, pyramidal effacement, and parenchymal thinning. (Courtesy V. Nickeleit, MD.) |
 Gross photograph reveals distinct yellow striae in the medulla  , with congestion at the corticomedullary junction, of a kidney with acute uric acid nephropathy. (Courtesy V. Nickeleit, MD.) |
TERMINOLOGY
Abbreviations
Uric acid nephropathy (UAN)
Synonyms
Urate nephropathy, gouty nephropathy with tophi, gout nephropathy
Definitions
Intrarenal precipitation of uric acid associated with hyperuricemia or hyperuricosuria
ETIOLOGY/PATHOGENESIS
Normal Metabolism
Uric acid is final degradation product of purine metabolism
Sources are endogenous from adenine or guanine nucleotides or exogenous from diet
Uric acid can be generated in all cells but most markedly by hepatocytes
Urate is filtered freely, reabsorbed, secreted, and undergoes post-secretory reabsorption, all in proximal tubules
10% of filtered load is excreted in urine
Hyperuricemia
Defined as plasma uric acid > 7 mg/dL
Due to
Decreased excretion (75-90%)
Overproduction (10-25%)
Decreased tubular secretion/increased reabsorption
Idiopathic
Drugs: Thiazide diuretics, cyclosporine A, low dose salicylates
Chronic heavy metal toxicity: Lead (saturnine gout), beryllium
Metabolic: Ketoacidosis, lactic acidosis, dehydration, Bartter syndrome, chronic renal failure
Endocrine: Hypothyroidism, hyperparathyroidism
Genetic: Familial juvenile hyperuricemic nephropathy (uromodulin storage disease)
Miscellaneous: Sickle cell anemia, Down syndrome, sarcoidosis, eclampsia
Overproduction/excessive release
Idiopathic (60%)
Massive tissue destruction
Hematologic diseases: Leukemia, lymphoma, myeloma, polycythemia
Tumor lysis syndrome: Treatment of leukemia, lymphoma, multiple myeloma, and solid tumors with cytotoxic agents or radiation
Crush injury, rhabdomyolysis, seizures (prolonged, severe)
Hereditary enzyme deficiencies
X-linked: Hypoxanthine guanine phosphoribosyl transferase deficiency; complete (Lesch-Nyhan syndrome) or partial
Autosomal recessive: Glucose-6-phosphatase deficiency in glycogen storage disease type 1
Hyperuricemia and Kidney Disease
Deposits of uric acid in tissue are in form of monosodium urate monohydrate or rarely ammonium urate
Deposits are doubly refractile on polarization microscopy
Kidney is involved in 3 ways
Intratubular uric acid deposits: Acute UAN
Interstitial deposits: Chronic UAN
Lithiasis: Uric acid or mixed uric acid and calcium oxalate stones
Severe hyperuricemia (plasma levels 20-50 mg/dL)
Associated with tissue destruction, hematologic disease, enzyme deficiency
Marked hyperuricosuria exceeds urinary solubility with resultant precipitation
May be compounded by acidic urine, high urinary calcium phosphate in cases with tissue destruction
Usually associated with acute UAN
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