Inhibition of the Progression of Chronic Kidney Disease With Hyperuricemia

Abstract

The final product of the catabolism of purine compounds in humans is uric acid (UA), which is a weak organic acid, over 98% of which is ionized into monosodium urate. UA is excreted by the kidneys, approximately 80-99% is reabsorbed in the proximal tubules of the kidneys. About 20% of UA is excreted through the intestine, where it is destroyed by microflora to carbon dioxide and water. The reference value of UA in blood plasma is 6.5-7 mg/dl in men and 6–6.5 mg/dl in women. The content of UA in the range of 360-400 μmol/l or 6-6.8 mg / dl increases the risk of crystallization under physiological conditions, and regardless of gender. UA levels greater than 7.0 mg/dl are associated with an increased risk of developing gout or nephrolithiasis. Hyperuricemia may occur due to increased production and / or decreased renal excretion of UA. Hyperuricemia is high in the general population and is associated with the development and progression of chronic kidney disease (CKD). Currently, allopurinol and febuxostat are used to correct hyperuricemia. The use of allopurinol should begin with a low dose (50-100 mg/day) and gradually titrate until the target level of UA in the blood is reached or until it is reached to the maximum. If necessary, the dose of allopurinol is increased by 100 mg every 2–4 weeks until the target serum UA level is reached. According to EULAR's recommendations for the treatment of gout, if the target level of UA cannot be achieved with an adequate dose of allopurinol, it should be replaced with febuxostat or uricosuric or a combination of febucostat with uricosuric. Febuxostat is also indicated for allopurinol intolerance. Febuxostat in doses of 80 and 120 mg/day was more effective than allopurinol at a dose of 300 mg/day. With CKD with mild or moderate renal failure, as well as in the elderly, it is not necessary to adjust the dose of febuxostat. The likelihood of reaching the target level of UA in the blood with reduced kidney function is higher in febuxostat. If the patient does not have serious cardiovascular diseases, the patient can be transferred to febuxostat, starting with a dose of 40 mg/day, and gradually titrated, especially in the case of CKD.