Purines are natural substances found in all of the body's cells and in virtually all foods. In humans, purines are metabolized to uric acid, which serves as an antioxidant and helps to prevent damage caused by active oxygen species. A continuous supply of uric acid is important for protecting human blood vessels. However, frequent and high intake of purine-rich foods reportedly enhances serum uric acid levels, which results in gout and could be a risk factor for cardiovascular disease, kidney disease, and metabolic syndrome. In Japan, the daily intake of dietary purines is recommended to be less than 400 mg to prevent gout and hyperuricemia. We have established an HPLC method for purine analysis and determined purines in a total of 270 foodstuffs. A relatively small number of foods contained concentrated amounts of purines. For the most part, purine-rich foods are also energy-rich foods, and include animal meats, fish meats, organs such as the liver and fish milt, and yeast. When the ratio of the four purine bases (adenine, guanine, hypoxanthine, and xanthine) was compared, two groups of foods were identified: one that contained mainly adenine and guanine and one that contained mainly hypoxanthine. For patients with gout and hyperuricemia, the amount of total purines and the types of purines consumed, particularly hypoxanthine, are important considerations. In this context, the data from our analysis provide a purine content reference, and thereby clinicians and patients could utilize that reference in nutritional therapy for gout and hyperuricemia.

BackgroundThe role of uric acid (UA) in the progression of chronic kidney disease (CKD) remains controversial due to the unavoidable cause and result relationship. This study was aimed to clarify the independent impact of UA on the subsequent risk of end-stage renal disease (ESRD) by a propensity score analysis.MethodsA retrospective CKD cohort was used (n = 803). Baseline 23 covariates were subjected to a multivariate binary logistic regression with the targeted time-averaged UA of 6.0, 6.5 or 7.0 mg/dL. The participants trimmed 2.5 percentile from the extreme ends of the cohort underwent propensity score analyses consisting of matching, stratification on quintile and covariate adjustment. Covariate balances after 1:1 matching without replacement were tested for by paired analysis and standardized differences. A stratified Cox regression and a Cox regression adjusted for logit of propensity scores were examined.ResultsAfter propensity score matching, the higher UA showed elevated hazard ratios (HRs) by Kaplan-Meier analysis (≥6.0 mg/dL, HR 4.53, 95%CI 1.79–11.43; ≥6.5 mg/dL, HR 3.39, 95%CI 1.55–7.42; ≥7.0 mg/dL, HR 2.19, 95%CI 1.28–3.75). The number needed to treat was 8 to 9 over 5 years. A stratified Cox regression likewise showed significant crude HRs (≥6.0 mg/dL, HR 3.63, 95%CI 1.25–10.58; ≥6.5 mg/dL, HR 3.46, 95%CI 1.56–7.68; ≥7.0 mg/dL, HR 2.05, 95%CI 1.21–3.48). Adjusted HR lost its significance at 6.0 mg/dL. The adjustment for the logit of the propensity scores showed the similar results but with worse model fittings than the stratification method. Upon further adjustment for other covariates the significance was attained at 6.5 mg/dL.ConclusionsThree different methods of the propensity score analysis showed consistent results that the higher UA accelerates the progression to the subsequent ESRD. A stratified Cox regression outperforms other methods in generalizability and adjusting for residual bias. Serum UA should be targeted less than 6.5 mg/dL.

Abbreviations & AcronymsObjectives: To analyze the crystal components and matrix proteins of urinary stones by proteomic analysis using liquid chromatography-tandem mass spectrometry. Methods: Urinary stones were obtained from patients with gout and hyperuricemia. The outside and inside of the stones were measured non-destructively with a micro area X-ray diffractometer. After stones were powdered , extracted proteins were analyzed by proteomic analysis. Results: Of 17 investigated stones, seven were composed of calcium oxalate monohydrate or calcium oxalate dihydrate, seven were of uric acid , and three were a mixture of calcium oxalate monohydrate and uric acid. In calcium oxalate monohydrate or calcium oxalate dihydrate stones, osteopontin, uromodulin, albumin, protein Z, prothrombin, protein S, hemoglobin and histone H4 were identified. In uric acid stones, uromodulin, albumin, hemoglobin, calgranulins and immunoglobin G fragments were detected. Mixed stones of calcium oxalate monohydrate and uric acid contained both Ca-binding proteins and abundant proteins. Matrix proteins were different when the crystal components of the stone were different, even when from the same patient. Conclusions: Proteins, such as uromodulin and albumin, are often detected in stones, regardless of crystal components. However, osteopontin, prothrombin, protein S and protein Z are identified specifically in calcium oxalate stones. Furthermore, immunoglobin G fragments are detected in uric acid stones. The role of these specific proteins in the different types of stones can be of particular interest.

It is well accepted that frequent and heavy intake of purine-rich foods causes elevation of serum uric acid levels, which is a risk factor of hyperuricemia. Reducing intestinal absorption of dietary purines may attenuate the elevation of serum uric acid levels and exacerbation of hyperuricemia. This reduction may be achieved by the ingestion of lactic acid bacteria that take up purines in the intestine. In this study, we investigated the degree of uptake and utilization of purines of three lactobacilli strains. Among them, Lactobacillus gasseri PA-3 (PA-3) showed the greatest incorporation of C-adenine. PA-3 also incorporatedC-adenosine and C-AMP. Additionally, using defined growth medium, PA-3 demonstrated greater proliferation in the presence of these purines than in their absence. Although further investigation is required, ingestion of PA-3 may lower serum uric acid levels by reducing intestinal absorption of purines in humans.

In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid) in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs), i.e., 421C>A (major) and 376C>T (minor), in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare.