Non-urate transporter 1, non-glucose transporter member 9-related renal hypouricemia and acute renal failure accompanied by hyperbilirubinemia after anaerobic exercise: a case report

Abstract

BackgroundRenal hypouricemia (RHUC) is an inherited heterogenous disorder caused by faulty urate reabsorption transporters in the renal proximal tubular cells. Anaerobic exercise may induce acute kidney injury in individuals with RHUC that is not caused by exertional rhabdomyolysis; it is called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE).RHUC is the most important risk factor for ALPE. However, the mechanism of onset of ALPE in patients with RHUC has not been elucidated. The currently known genes responsible for RHUC are SLC22A12 and SLC2A9.Case presentationA 37-year-old man presented with loin pain after exercising. Despite having a healthy constitution from birth, biochemical examination revealed hypouricemia, with a uric acid (UA) level of < 1 mg/dL consistently at every health check. We detected acute kidney injury, with a creatinine (Cr) level of 4.1 mg/dL, and elevated bilirubin; hence, the patient was hospitalized. Computed tomography revealed no renal calculi, but bilateral renal swelling was noted. Magnetic resonance imaging detected cuneiform lesions, indicating bilateral renal ischemia. Fractional excretion values of sodium and UA were 0.61 and 50.5%, respectively. Urinary microscopy showed lack of tubular injury. The patient’s older sister had hypouricemia. The patient was diagnosed with ALPE. Treatment with bed rest, fluid replacement, and nutrition therapy improved renal function and bilirubin levels, and the patient was discharged on day 5. Approximately 1 month after onset of ALPE, his Cr, UA, and TB levels were 0.98, 0.8, and 0.9 mg/dL, respectively. We suspected familial RHUC due to the hypouricemia and family history and performed genetic testing but did not find the typical genes responsible for RHUC. A full genetic analysis was opposed by the family.ConclusionsTo the best of our knowledge, this is the first report of ALPE with hyperbilirubinemia. Bilirubin levels may become elevated as a result of heme oxygenase-1 activation, occurring in exercise-induced acute kidney injury in patients with RHUC; this phenomenon suggests renal ischemia-reperfusion injury. A new causative gene coding for a urate transporter may exist, and its identification would be useful to clarify the urate transport mechanism.

Clinical features suggesting renal hypouricemia as the cause of acute kidney injury: a case report and review of the literature

“…According to local availability and confidence in interpreting the results, direct genotyping with Sanger sequencing can even be considered as an early-option diagnostic tool to provide rapid genetic results and a definitive diagnosis of the disease. Of note, Sanger sequencing failed to identify pathogenic variants in three patients (8%) with a clinical picture of RHUC-AKI included in our cohort analysis [ 10 , 11 ]. In the future, MPS could be considered in order to identify additional genes involved in the pathogenesis of RHUC and to perform reliable genotype–phenotype correlations.…”

Acute kidney injury in rural workers: An environmental-stress nephropathy

“…The tendency for intra-tubular precipitation is intensified by the elevated concentration and acidity of urine in this environment [13,14]. There are different mechanisms through which uric acid can cause kidney injury, such as: renal autoregulation alteration, intra-renal vasoconstriction, endothelial dysfunction, as well as uric acid pro-inflammatory (increased IL-6) and pro-oxidative effects [15][16][17][18][19][20]. Third, regarding the hypothesis that recurrent heat stress (heat stroke) could lead to renal damage, it has been postulated that it could act by promoting critical fluid contraction, muscle thermal damage, as well as vasoconstrictor substances release [13,21].…”

“…Finally, the documented significantly reduced afternoon serum uric acid values compared to their morning ones, could be explained by some degree of proximal tubule dysfunction (acquired or primary tubulopathy) and increased urinary uric acid loss or intratubular precipitation. Uric acid intratubular precipitation could be promoted by dehydration [16][17][18][19][20]. As it was mentioned above, intratubular uric acid accumulation can induce tubular damage by promoting local ischemia, inflammation, and oxidative stress [15,20,25].…”

Effect of high-altitude hypoxia environment on uric acid excretion, Desmin protein level in podocytes, and Na+-K+- ATPase activity

“…The low oxygen content in the plateau environment has a series of effects on the body's organs and tissues, including changes in blood biochemistry, rheology, and blood gas (33). The kidney, as an organ to maintain the stability of the internal environment of the body, will be damaged in the hypoxia environment, resulting in pathological changes (34).…”