Uric acid nephropathy 신장내과 R4 최선영

Endogenous production of uric acid Purine catabolism hypoxanthine xanthine Uric acid allantoin XO UO allopurinol - - Exogenous urate oxidase +

Urate handling by kidney model

Acute uric acid nephropathy Hyperuricemia  rapid decline in renal function Pathogenesis Sludging and precipitation of uric acid crystals within the tubule of distal nephrone Dehydration, ECFV depletion  urine acid concentration increases in tubule fluid and urine  severe uric acid nephropathy

Massive urate overproduction – endogenous excessive purine and urate biosynthesis massive tissue destruction (rhabdomyolysis, tumor lysis syndrome) Supportive care : hydration, loop diuretics, allopurinol, correction of metabolic disturbance, urinary alkalinization, hemodialysis Uricase (rasburicase) Exogenous urate overproduction Ingesting an excessively high amount of dietary purine Usually milder and more chronic

Chronic hyperuricemic nephropathy Deposition of sodium urate crystals in the medullary interstitium  chronic inflammatory response  interstitial fibrosis and CRF

Familial gout syndrome Renal parenchymal MSU deposits along with interstitial nephritis Marked urate overproduction Interstitial MSU and intratubular uric acid deposits

Asymptomatic hyperuricemia Gout or kidney stone incidence – low Hyperuricemic hypertension Renal clearance of urate ↓ Intrarenal vascular disease  renal blood flow ↓ Insulin resistance Insulin : renal urate clearance ↓ (reabsorption) Hyperinsulinemia – hyperuricemia – vascular disease – salt-dependent hypertension

Uric acid nephrolithiasis Uric acid stone Nonopaque on radiologic examination 5-10% of all urinary stones in the USA, Europe >40% in areas with hot and arid climates High serum uric acid levels Low urinary pH and low fractional excretion of urate

Pathogenesis High concentration of uric acid Acid urine pH H(+) + Urate(-) (soluble)  Uric acid (insoluble) Total uric acid solubility in the urine 200mg/dL at urine pH mg/dL at urine pH 5.0

Diagnosis Acute onset of flank pain, positive CT for stone, history of a predisposing underlying disease (gout..) Chemical analysis of a stone 24-hr urine collection – hyperuricosuria Treatment Urine output >2L/day Alkalinization of the urine (urine pH>6.5) Administration of allopurinol

Causes of secondary hyperuricemia due to increased purine biosyntaesis and/or urate production Inherited enzyme defects leading to purine overproduction Hypoxanthine-guanine phosphribosyltransferase deficiency Phosphoribosylpyrophosphate synthetase overactivity Glucose-6-phosphatase deficiency (glycogen storage disease, type 1) Clinical disorders leading to purine and/or urate overproduction Myeloproliferative disorders Lymphoproliferative disorders Malignancies Hemolytic disorders Psoriasis Obesity Tissue hypoxia Down syndrome Glycogen storage disease (types III, V, VII) Drug-, diet-, or toxin-induced purine and/or urate overproduction Ethanol Excessive dietary pyrine ingestion Pancreatic extract Fructose Vitamin B12 deficiency Nicotinic acid Ethylamino-1,3,4-thiadiazole 4-amino-5-imidazole carboxamide riboside Cytotoxic drugs warfarin