RESUMEN
Abstract Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.
Resumo A hiperuricemia é comum na doença renal crônica (DRC) e pode estar presente em até 50% dos pacientes que se apresentam para diálise. A hiperuricemia pode ser secundária ao comprometimento da taxa de filtração glomerular (TFG) que ocorre na DRC. No entanto, ela também pode preceder o desenvolvimento da doença renal e mesmo prever uma DRC incidente. Estudos experimentais de modelos hiperuricêmicos descobriram que tanto o ácido úrico solúvel quanto o cristalino podem causar danos renais significativos, caracterizados por isquemia, fibrose tubulointersticial e inflamação. Entretanto, a maioria dos estudos de randomização Mendeliana falhou em demonstrar uma relação causal entre o ácido úrico e a DRC, e os ensaios clínicos têm apresentado resultados variáveis. Aqui sugerimos explicações potenciais para os achados clínicos e genéticos negativos, incluindo o papel do ácido úrico cristalino, do ácido úrico intracelular e da atividade da xantina oxidase na lesão renal mediada por ácido úrico. Propomos ensaios clínicos futuros, bem como um algoritmo para o tratamento de hiperuricemia em pacientes com DRC.
Asunto(s)
Humanos , Hiperuricemia/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Ácido Úrico , Diálisis Renal , Tasa de Filtración GlomerularRESUMEN
Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.