The world- first clinical practice guideline (CPG) for renal hypouricemia (RHUC) has developed from Japan along MINDS methodology last year. Its first goal is to clarify the criteria for diagnosing RHUC, and another goal is to work towards a consensus on clinical decision-making.
RHUC is caused by a dysfunction of renal urate reabsorption. It does not include congenital purine metabolism abnormalities or secondary hypouricemia, and is relatively common (0.3%) in Japanese populations. Genetic analyses have demonstrated its causes as dysfunctional variants in urate reabsorption transporter URAT1/SLC22A12 and/or GLUT9/SLC2A9 genes, but there should be unknown causative genes. One of the characteristics of RHUC is a low serum uric acid (SUA) level with increased renal excretion of uric acid. CPG proposed its clinical diagnostic guidance for RHUC along clinical algorithm, which enables easy diagnosis with simple tests. RHUC itself is usually asymptomatic, but exercise-induced acute kidney injury (EIAKI, also known as “ALPE”) and urolithiasis are well-known complications. EIAKI cases generally show transient and recurrent acute kidney injury (AKI), and receive common treatment for AKI. For urinary stones, urinary alkalization and citrate compounds are effective therapies and fluid intake is recommended for prevention.
We strongly recommend that individuals with an SUA of ≤ 2.0 mg/dl (120 µmol/l) be considered for differential diagnosis of hypouricemia. Some studies reports that allopurinol, a xanthine oxidoreductase (XOR) inhibiter, was administered as prevention for EIAKI, but due to low evidence, we cannot definitively state that XOR inhibitors are effective. It should be therefore decided in the light of its potential benefits and harms.
We hope that this CPG helps both healthcare providers and patients make clinical decisions, and will also promote the researches on RHUC.
Objective: Ingestion of yogurt containing Lactobacillus gasseri PA-3 (PA-3, Accession No: NITE BP-224) (PA-3Y) has been shown to reduce serum uric acid (SUA) levels by interfering with the intestinal absorption of food-derived purines in animal studies. To confirm this mechanism in humans, the ability of PA-3 intake to alleviate purine ingestion-induced increases in SUA levels was analyzed.
Research Methods and Procedures: In this randomized, double-blind, placebo-controlled crossover study, 16 healthy adults were randomized to groups ingesting of 112 g of PA-3Y or yogurt without PA-3 (control yogurt) in addition to standardized meals for 3 days. Purine-loading tests, in which subjects ingested 112 g of PA-3Y or control yogurt followed immediately by 498 mg of a mixture of purine nucleotides, were performed on the fourth day of each test period. Blood and urine samples were collected before and after the purine-loading tests.
Results: The increase in the SUA concentration from the baseline was significantly lower following the ingestion of PA-3Y than of control yogurt alone, especially at 30 (P=0.033) and 60 (P=0.028) minutes.In addition, the area under the curve for the increase in the SUA concentration from the baseline to 150 minutes was also significantly lower (P=0.041) in the PA-3Y than in the control yogurt group. However, urinary and fractional excretions of uric acid were not different between the two groups.
Conclusion: The ingestion of PA-3 before purine intake alleviates the increase in SUA levels, probably by reducing purine absorption in the intestine, and not by enhancing urinary excretion of uric acid.
Objective: To examine whether the supplementation of inosine augments ATP in vitro in human erythrocytes incubated in saline.
Methods: Peripheral blood was drawn from each of three subjects, i.e. one healthy male and two males with thalassemia and hemoglobinopathy. After washing the erythrocytes in saline, they were suspended in saline to which inosine was added to final concentrations of 0, 0.5 and 2.5 mM. The suspension was incubated at 37 °C for 1 or 3 hours, and 0.5 ml ice cold 8% perchloric acid was added to the 0.5 ml erythrocyte-containing solution. After removing precipitates and perchloric acid, the supernatant was submitted to HPLC for the measurement of ATP.
Results : Since the blood samples of the two subjects with thalassemia and hemoglobinopathy were transported from the clinics to the laboratory, ATP in the blood decreased considerably during the transportation. However, the reduction of ATP with time was observed in the erythrocytes in saline obtained from each of the three subjects during the incubation from 1 hour to 3 hours. In addition, dose-dependent suppression of the decrease of ATP with inosine was observed in all the three cases at both 1 hour and 3 hour incubation times.
Conclusions: Incubation of erythrocytes from a healthy subject and two thalassemia/hemoglobinopathy patients in saline at 37 °C resulted in time-dependent decreases of ATP. Supplementation of inosine to the solutions resulted in the suppression of the decreases of ATP in a dose-dependent manner.