Hypothetical Mechanism of Exercise-Induced Acute Kidney Injury Associated with Renal Hypouricemia.

Makoto Hosoyamada

doi:10.3390/biomedicines9121847

Abstract

Renal hypouricemia (RHUC) is a hereditary disease that presents with increased renal urate clearance and hypouricemia due to genetic mutations in the urate transporter URAT1 or GLUT9 that reabsorbs urates in the renal proximal tubule. Exercise-induced acute kidney injury (EIAKI) is known to be a complication of renal hypouricemia. In the skeletal muscle of RHUC patients during exhaustive exercise, the decreased release of endothelial-derived hyperpolarization factor (EDHF) due to hypouricemia might cause the disturbance of exercise hyperemia, which might increase post-exercise urinary urate excretion. In the kidneys of RHUC patients after exhaustive exercise, an intraluminal high concentration of urates in the proximal straight tubule and/or thick ascending limb of Henle’s loop might stimulate the luminal Toll-like receptor 4–myeloid differentiation factor 88–phosphoinositide 3-kinase–mammalian target of rapamycin (luminal TLR4–MyD88–PI3K–mTOR) pathway to activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and may release interleukin-1β (IL-1β), which might cause the symptoms of EIAKI.

Highlights

Renal hypouricemia type 2 (RHUC2): The renal urate clearance increases due to a decrease in the function of GLUT9, a transporter that excretes urates at the basal side of the proximal tubule cells to the interstitium [3]
Multiple cases of Exercise-induced acute kidney injury (EIAKI) have been reported in both types 1 and 2 of renal hypouricemia; there is no significant difference in the degree of renal damage between types 1 and 2
In we the will future study, will have identify segments the nephron segments where will be the future study, have to we identify the to nephron where pro-IL-1β pro-IL-1β will be expressed after an exhaustive exercise load in the kidneys of Renal hypouricemia type 1 (RHUC1) expressed after an exhaustive exercise load in the kidneys of RHUC1 model mice

Summary

Introduction

Exercise-induced acute kidney injury (EIAKI) is a complication of renal hypouricemia. It was considered that probenecid might inhibit the urate uptake by the OAT1 [8] and OAT3 [9] transporters, which are the entrances of urate secretion on the basal side of the proximal tubule, resulting in the suppression of urate secretion This patient and 4 healthy controls were subjected to exhaustive exercise and urine was collected at 1 h, 4 h and 24 h after the exercise to examine the urinary urate excretion. When all five subjects were administered 300 mg of allopurinol daily for 5 days and re-exercised, the patient no longer had an acute kidney injury and the urate excretion/creatinine excretion ratio remained unchanged from 0.25 before exercise to 0.17 after exercise. Figures are from the reference [10]

EIAKI Due to Increased Urate Excretion after Exhaustive Exercise

Hypothetical

IL-1β Production and Acute Kidney Injury

Increased Urinary Urate Excretion Due to Exercise

Findings

Post-Exercise Urate Production in Patients with Renal Hypouricemia