Urinary Uric Acid Excretion Research Articles

Changes in Urine Parameters After Desert Exposure: Assessment of Stone Risk in United States Marines Transiently Exposed to a Desert Environment

Living in a desert environment has been associated with a higher incidence of kidney stone formation, likely because of concentrated urine output, higher production of vitamin D and genetic predisposition. We determined the changes in urinary parameters after a group of United States Marines temporarily transitioned from a temperate environment to a desert environment. A total of 50 Marines completed a questionnaire and performed 3, 24-hour urine collections before mobilization to the desert, after 30 days in the desert and 2 weeks after returning from the desert. Daily urine output decreased 68% to 0.52 L despite marked increased fluid intake (17 L per day). Total daily urinary excretion of calcium, uric acid, sodium, magnesium and potassium in the desert decreased by 70%, 41%, 53%, 22% and 36%, respectively. Urinary pH decreased from 6.1 to 5.6 while in the desert, and citrate and oxalate had minimal changes. After their return from the desert, apart from a decrease of 22% in oxalate, there were no statistically significant differences from baseline. While in the desert, relative supersaturation risks of uric acid and sodium urate were increased 153% and 56%, respectively. Brushite relative supersaturation decreased 24%. After their return there was no statistical difference from baseline. Our findings suggest that the kidneys preserved water and electrolytes while the Marines were subjected to the desert environment. Despite this conservation, relative saturations indicate increased risk of stones in healthy men exposed to a desert environment with rapid resolution upon return.

563 COMPARISON OF EFFECTS OF LOSARTAN 50 MG/HYDROCHLOROTHIAZIDE 12.5 MG AND CANDESARTAN 8 MG/ HYDROCHLOROTHIAZIDE 6.25 MG ON PLASMA LEVELS AND URINARY EXCRETION OF URIC ACID IN JAPANESE HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS

Background and Objective: To see effects of losartan and hydrochlorothiazide (HCTZ) on uric acid metabolism, Methods: In patients with hypertension and type 2 diabetes mellitus who have already received a combination therapy with losartan 50 mg plus hydrochlorothiazide (HCTZ) 12.5 mg (Preminent®) and their blood pressure (BP) was controlled to < 130/80 mmHg, antihypertensive drug was switched to candesartan 8 mg plus HCTZ 6.25 mg (Ecard HD®) for 2 months and then switched back to Preminent®) for another 2 months. Results: BP was not altered between two regimens. However, plasma levels of uric acid (UA) was increased from 5.5 ± 1.2 (SD) to 5.9 ± 1.3 (p = 0.108) after changing to Ecard HD®), and then returned to 5.5 ± 1.2 mg/dl after switching back to Preminent®) (p = 0.017). Urinary excretion of UA (corrected by creatinine) was decreased from 0.54 ± 0.25 to 0.47 ± 0.20 (p = 0.046) after changing to Ecard HD®, and then returned to 0.66 ± 0.49 after switching back to Preminent®)(p = 0.038). Conclusions: Based on losartan's inhibitory action on UA reabsorption via URAT-1, these results suggest that an ability of 50 mg of losartan to decrease plasma UA level might be greater than that of 6.25 mg (the difference between two regimens) of HCTZ to increase plasma UA level, indicating that taking such a small difference of the amount of HCTZ into consideration for the treatment of hypertensive patients, especially associated with hyperuricemia and/or chronic kidney disease, is very important.

Absence of SLC22A12/URAT1 Gene Mutations in Patients with Primary Gout

To the Editor: In most patients with primary gout, hyperuricemia has been related to a decreased urinary uric acid excretion, but the specific gene abnormalities that may cause an impaired tubular transport of urate are unknown. The first urate transporter described was SLC22A12/URAT1 1. Mutations in the SLC22A12/URAT1 gene have been associated to primary renal hypouricemia type I (OMIN 220150) in several populations1,2,3,4,5, although some ethnic differences may explain the lack of association between this gene and primary renal hypouricemia in other populations such as Greek whites6. Because this transporter reabsorbs urate from the renal tubule, loss of function mutations may cause renal urate wasting and hypouricemia. However, it has been reported that among 69 Mexican patients with primary … Address correspondence to Dr. R.J. Torres, Servicio de Bioquímica, Edificio Laboratorio, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain. E-mail: rtorres.hulp{at}salud.madrid.org

Hypouricemic effects of novel concentrative nucleoside transporter 2 inhibitors through suppressing intestinal absorption of purine nucleosides

We have developed concentrative nucleoside transporter 2 (CNT2) inhibitors as a novel pharmacological approach for improving hyperuricemia by inhibiting intestinal absorption of purines. Dietary purine nucleosides are absorbed in the small intestines by CNTs expressed in the apical membrane. In humans, the absorbed purine nucleosides are rapidly degraded to their final end product, uric acid, by xanthine oxidase. Based on the expression profile of human CNTs in digestive tract tissues, we established a working hypothesis that mainly CNT2 contributes to the intestinal absorption of purine nucleosides. In order to confirm this possibility, we developed CNT2 inhibitors and found that (2R,3R,4S,5R)-2-(6-amino-8-{[3'-(3-aminopropoxy)-biphenyl-4-ylmethyl]-amino}-9H-purin-9-yl)-5-hydroxymethyl-tetrahydrofuran-3,4-diol (KGO-2142) and 1-[3-(5-{[1-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-1H-benzimidazol-2-ylamino]-methyl}-2-ethoxyphenoxy)-propyl]-piperidine-4-carboxylic acid amide (KGO-2173) were inhibitory. These CNT2 inhibitors had potent inhibitory activity against inosine uptake via human CNT2, but they did not potently interfere with nucleoside uptake via human CNT1, CNT3 or equilibrative nucleoside transporters (ENTs) in vitro. After oral administration of KGO-2173 along with [14C]-inosine, KGO-2173 significantly decreased the urinary excretion of radioactivity at 6 and 24h in rats. Since dietary purine nucleosides are not utilized in the body and are excreted into the urine rapidly, this decrease in radioactivity in the urine represented the inhibitory activity of KGO-2173 toward the absorption of [14C]-inosine in the small intestines. KGO-2142 almost completely inhibited dietary RNA-induced hyperuricemia and the increase in urinary excretion of uric acid in cebus monkeys. These novel CNT2 inhibitors, KGO-2142 and KGO-2173, could be useful therapeutic options for the treatment of hyperuricemia.

Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid.

BackgroundThe finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances.MethodsWithin the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum.Results and discussionUrine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine.ConclusionWe conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.

Clinical experience with Uralyt-U used in patients with gout and nephrolithiasis

The impact of a 4-week course of therapy with Uralyt-U (potassium-sodium hydrocitrate) on uric acid (UA) metabolic parameters was studied in patients with gout and nephrolithiasis. Elevated daily urinary excretion of UA was found to be directly correlated with its lower serum level after 4-week therapy with Uralyt-U (p &lt; 0.05), resulting in improvement and normalization of UA metabolism. Uralyt-U therapy is safe and causes no worsening of the parameters of hepatic and renal function and electrolyte exchange.

Protocol-based metabolic evaluation in high-risk patients with renal stones in North India

Context:Renal calculus disease has a lifetime recurrence rate of 80%. Protocol-based metabolic evaluation in high-risk subjects for recurrent renal stones reveals abnormalities in a large subset of subjects. However, such information is not available in Indian subjects.Aims:To evaluate the abnormalities by a protocol-based metabolic evaluation in patients at a high risk for recurrent renal stones.Settings and Design:Prospective, academic tertiary care center.Materials and Methods:Fifty North Indian patients (38 males and 12 females; mean age 38 ± 10.2 years) with recurrent or bilateral renal stones were evaluated. All subjects underwent a protocol-based evaluation involving estimation of serum total calcium, phosphorus, creatinine, albumin, iPTH, 25(OH)D3, 1,25(OH)2D3, and a calcium load test. Estimation of daily urinary excretion of volume, oxalate, calcium, uric acid, and citrate, and urinary acidification studies were performed.Statistical Analysis Used:Descriptive statistics and t-test.Results:An underlying disorder was detected in 48 (96%) patients. Almost half had two or more metabolic abnormalities. The metabolic abnormalities detected were: Hypercalciuria 26 (52%) patients, renal hypercalciuria 16 (32%), absorptive hypercalciuria 6 (12%), unclassified hypercalciuria 4 (8%), hyperoxaluria 27 (54%), hyperuricosuria 9 (18%), distal renal tubular acidosis 4 (8%; 2 complete and 2 partial), primary hyperparathyroidism 3 (6%), and hypocitraturia 14 (n=18, 77%). In two patients, the etiology could not be detected.Conclusions:Protocol-based metabolic evaluation reveals metabolic abnormalities in majority of patients with nephrolithiasis. The spectrums of metabolic abnormalities are different in Indian subjects as compared to the western population.

Evaluation and Characterization of the Effects of Ticagrelor on Serum and Urinary Uric Acid in Healthy Volunteers

During its development, ticagrelor, a drug designed to prevent thrombotic events in patients with acute coronary syndromes, was found to have an association with mild hyperuricemia. To investigate this effect further, we carried out a placebo-controlled, randomized, crossover study in 24 healthy male volunteers. The volunteers received ticagrelor (90 mg b.i.d. for 5 days), and serum uric acid and urinary uric acid excretion were assessed under strictly controlled conditions. After administration of ticagrelor, serum uric acid significantly increased (day 1: 4-6%; day 5: 4-10%) relative to placebo and rapidly returned to baseline after the last dose of the drug. Urinary uric acid excretion was significantly higher on day 1 (7%) and at 24-48 h after the morning dose on day 5 (17%) relative to placebo. Uric acid clearance was significantly higher 24-48 h after the morning dose on day 5 (11%). Uric acid fractional excretion was unaffected. Serum hypoxanthine and xanthine were elevated after multiple ticagrelor doses. No uric acid-related adverse events were seen. The study showed that ticagrelor-associated hyperuricemia is modest and reversible; serum uric acid elevation may have been caused by altered tubular secretion and/or increase in production.

Early Markers of Tubular Dysfunction in Antiretroviral-Experienced HIV-Infected Patients Treated with Tenofovir Versus Abacavir

Tenofovir disoproxil fumerate (TDF) is an effective nucleoside reverse transcriptase inhibitor for HIV infection but it is potentially nephrotoxic. A selective mithochondrial toxicity has been hypothesized. To assess early markers of renal toxicity, we evaluated a cohort of antiretroviral (ARV)-experienced HIV patients who had been switched from a thymidinic backbone to either a TDF/emtricitabine regimen (TDF; 73 patients) or an abacavir/lamivudine (ABV) regimen (28 patients). Markers of mitochondrial toxicity (cytochrome c, Cyc) or cytosolic (α-glutathione S transferase, α-GST) together with common indicators of renal damage were assessed at baseline (T0) and after 1 (T1), 3 (T2), 6 (T3), and 12 (T4) months of patient exposure to therapy. Clinical features of both groups were comparable at T0. There was no significant variation in estimated glomerular filtration rate (eGRF), median urine protein excretion, or microalbuminuria and serum phosphate levels in both groups during the study period. There was a significant increase in urinary excretion of phosphate in patients on TDF compared to those on ABV at T3 and T4. Fractional excretion of uric acid was also altered in the two treatment groups; there was no change in the ABV (constantly less than 0.10), but a progressive increase in TDF patients. Serum potassium levels were significantly lower in ABV than in TDF treated patients. Urine concentrations of α-GST showed a nonsignificant variation in both groups, while Cyc excretion was significantly higher at T1 and T3 in TDF-treated compared to ABV-treated patients. In conclusion, TDF may be associated with subclinical mitochondrial damage, inducing at a later stage increased urinary excretion of phosphate and uric acid, as markers of incipient tubular injury.

Acidosis with hyperuricemia and renal tubular damage in viral gastroenteritis

Acidosis with hyperuricemia and renal tubular damage in viral gastroenteritis

Uric acid excretion in healthy subjects: a nomogram to assess the mechanisms underlying purine metabolic disorders

The reference range for urinary uric acid excretion has not been precisely defined. Different urinary variables have been proposed to determine the renal contribution to increased or decreased serum urate concentrations. We examined which urinary variable best indicates uric acid excretion over a wide range of serum urate concentrations. Purine metabolism was studied in 10 healthy male subjects (aged 26-58 years) both at their endogenous normal serum urate levels (normouricemic state) and after the oral administration of allopurinol (300 mg/24 h for 5 days) and ribonucleic acid (4 g/8 h for 4 days) to decrease (hypouricemic state) and increase (hyperuricemic state) serum urate concentrations, respectively. The results from patients with several conditions known to affect uric acid synthesis and/or the renal excretion of uric acid were used to validate a constructed nomogram. Over a wide range of mean serum urate levels (from 2.7 to 9.5 mg/dL) and mean 24-hour urinary uric acid excretion (171 to 1368 mg/[24 h 1.73 m2]), the highest correlation coefficient between serum urate and uric acid excretion was obtained for the 24-hour uric acid determination (r = 0.928; P < .001). The constructed nomogram allowed the definition of the mechanism underlying hyperuricemia and hypouricemia in patients with a myriad of diseases known to affect purine metabolism. The urinary variable that best correlates with a wide range of serum urate concentrations is 24-hour urinary uric acid excretion. The constructed nomogram allows the identification of the kidney contribution to a given purine metabolic abnormality.

Urinary calcium and uric acid excretion in children with vesicoureteral reflux

Urolithiasis is relatively common in children, and identifiable predisposing factors for stone formation, including metabolic and structural derangements, can be established in most cases. Vesicoureteral reflux (VUR) is a common cause of kidney stone formation. The pathophysiological mechanism of urolithiasis in reflux is related to urinary tract infection and urinary stasis, both of which promote urinary crystal formation, but metabolic causes, such as crystallurias (mostly hypercalciuria), may also be involved in this process. However, few studies on urinary calcium and uric acid excretion in children with VUR have been conducted. We have studied the frequency of hypercalciuria and hyperuricosuria in children with VUR and compared the results with those from a control group. The VUR group comprised 108 children with VUR (19 boys, 89 girls; age range 3 months to 12 years), and the control group comprised 110 healthy children without any history of reflux or urinary tract infection (30 boys, 80 girls; age range 2 months to 12 years). Fasting urine was analyzed for the calcium/creatinine (Ca/Cr) and uric acid/creatinine (UA/Cr) ratios. Hypercalciuria was more frequently diagnosed in the VUR patients than in the control group (21.3 vs. 3.6%; P = 0.0001). Significant differences between the two groups were also found for the mean Ca/Cr and UA/Cr ratios (P = 0.0001 and P = 0.0001, respectively). No differences were found in the urinary Ca/Cr or UA/Cr ratios related to VUR grading or unilateral/bilateral VUR in the patient group, with the exception of those for hypercalciuria and mild VUR (P = 0.03). The association of urinary stones and microlithiasis in the VUR group was 29.6%. Our results demonstrate that the frequency of hypercalciuria and hyperuricosuria was higher in pediatric patients with VUR than in healthy children. Knowing this relationship, preventive and therapeutic interventions for stone formation in VUR could be greatly expanded.

Potential Pharmacologic Treatments for Cystinuria and for Calcium Stones Associated with Hyperuricosuria

Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to "salt out" (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent calcium stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of l-cystine methyl ester and l-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, l-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria.

Effects of bovine milk ingestion on urinary excretion of oxypurinol and uric acid

Although allopurinol is a xanthine oxidase inhibitor, its overall effect may be due to the action of oxypurinol, a metabolite of allopurinol and another xanthine oxidase inhibitor, since the biological half-life of oxypurinol is longer than that of allopurinol. Oxypurinol shares a renal transport pathway with uric acid and ingestion of bovine milk increases the urinary excretion of uric acid. Therefore, we investigated whether its ingestion promotes the urinary excretion of oxypurinol. Bovine milk (15 ml/kg body weight) was administered to 6 healthy subjects who took allopurinol (300 mg) 12 h prior to ingestion. In addition, a control experiment was performed with the same subjects using the same protocol, except for the ingestion of water instead of bovine milk. Blood and urine samples were collected before and after bovine and water ingestion. In the bovine milk ingestion experiment, the urinary excretion values of oxypurinol and uric acid were increased by 18% and 38%, respectively, and the fractional excretion values of oxypurinol and uric acid were increased by 20% and 40%, respectively, whereas those did not change in the control experiment. In addition, the concentration of alanine and sum of concentrations of amino acids were increased by 16% and 20%, respectively, in the bovine milk ingestion experiment. These results suggest that bovine milk ingestion promotes the urinary excretion of oxypurinol as well as uric acid by increasing amino acid concentration.

Effect of vitamin E therapy on serum uric acid in DOCA-salt-treated rats

Uric acid is considered as an antioxidant in the blood. Despite its proposed protective properties, elevated plasma uric acid has been associated with hypertension in a variety of disorders. The purpose of this study was to investigate the relationship between the increase of arterial blood pressure and the changes in serum uric acid, measured during the gradual development of experimental hypertension in deoxycorticosterone (DOCA)-salt-treated rats. Blood pressure was monitored by tail-cuff method, urinary and plasma uric acid was measured by autoanalyzer during the induction of hypertension in 1-, 2-, 3- and 4-week DOCA-salt-treated Sprague-Dawley rats. Vitamin E (200 mg/kg/day/gavage) was co-administered with DOCA-salt for 4 weeks. From the first week of DOCA-salt treatment, rats exhibited marked increases in blood pressure. DOCA-salt treatment also resulted in a significant increase in serum uric acid and a significant decrease in urinary uric acid at the end of the first week. These changes in serum and urinary uric acid remained until the 4th week of DOCA-salt treatment but blood pressure continued to increase throughout the study. Vitamin E treatment increased urinary excretion of uric acid and decreased blood pressure and serum uric acid in DOCA-salt-treated rats. These data suggest that enhanced serum uric acid may be a contributing factor to the onset of hypertension in DOCA-salt-treated rats. A uricosuric effect is suggested for vitamin E in the treatment of hypertension.

Low-fructose diet lowers blood pressure and inflammation in patients with chronic kidney disease

Fructose has been strongly linked with hypertension, hyperuricemia and inflammation in experimental models and humans. However, the effect of low-fructose diet on inflammation, hyperuricemia and the progression of renal disease has not yet been evaluated in patients with chronic kidney disease (CKD). Twenty-eight patients (age 59 ± 15 years, 17 males/11 females) with Stages 2 and 3 CKD were switched from a regular (basal) (60.0 g/24 h) to a low (12.0 g/24 h) fructose diet for 6 weeks, followed by a resumption of their regular diet for another 6 weeks. Diet was monitored by a dietician. At the baseline, low- and regular-fructose diet ambulatory blood pressure (BP) was measured and blood sampled for renal function (creatinine), inflammatory markers, fasting glucose and insulin and serum uric acid. Twenty-four-hour urine collections were also obtained for creatinine, uric acid, monocyte chemotatic protein-1, transforming growth factor-beta and N-acetyl-beta-D-glucosaminidase. The low-fructose diet tended to improve BP for the whole group (n = 28), while significant reduction of BP was only seen in dippers (n = 20) but not in non-dippers (n = 8). No effects on estimated glomerular filtration rate (eGFR) or proteinuria were observed. Serum uric acid was lowered non-significantly with low-fructose diet (7.1 ± 1.3 versus 6.6 ± 1.0 mg/dL, P < 0.1), whereas a significant decrease in fasting serum insulin was observed (11.2 ± 6.1 versus 8.2 ± 2.9 mIU/mL, P < 0.05) and the reduction persisted after return to the regular diet. A slight but not significant reduction in urinary uric acid and fractional uric acid excretion was observed while the patients were on the low fructose diet. The low-fructose diet also decreased high sensitivity C-reactive protein (hsCRP) (4.3 ± 4.9 versus 3.3 ± 4.5 mg/L; P < 0.01) and soluble intercellular adhesion molecule (sICAM) (250.9 ± 59.4 versus 227 ± 50.5 ng/mL; P < 0.05). The hsCRP returned to baseline with resumption of the regular diet, whereas the reduction in sICAM persisted. Low-fructose diet in subjects with CKD can reduce inflammation with some potential benefits on BP. This pilot study needs to be confirmed by a larger clinical trial to determine the long-term benefit of a low-fructose diet compared to other diets in subjects with CKD.

Diagnosis of Gout: Considering Clinical and Research Settings

The diagnosis of gout is usually straightforward and should normally rely upon the identification of monosodium urate crystals in synovial fluid. EULAR have recently developed consensus recommendations regarding the diagnosis of gout. Where examination of synovial fluid is not possible or impractical, the best approach differs depending upon the context: in clinical research, classification criteria are necessary whereas in clinical practice, all available information should be carefully weighed and considered by the physician. A number of clinical features are useful pointers towards the diagnosis of gout and ultrasound is emerging as a useful diagnostic tool. The finding of hyperechoic enhancement of the superficial margin of the hyaline cartilage is a sensitive and specific feature of gout, although the performance of ultrasound in early disease is unclear. Serum uric acid is not a useful test for the diagnosis of gout but is very important in the long-term management. The 1977 American Rheumatism Association classification criteria have many shortcomings and improved criteria are urgently required for epidemiology and clinical research. The complete diagnostic evaluation may involve assessment of 24-hour urinary excretion of uric acid in a few selected patients and all patients should be evaluated for common comorbidities especially the metabolic syndrome and risk factors for cardiovascular disease.

Higher Urinary Excretion of Inorganic Phosphate During Early Induction Chemotherapy Predicts a Good Prognosis in Childhood Acute Leukemia

The rapidity of response to induction therapy is emerging as an important prognostic factor in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Urine inorganic phosphate (IP) and uric acid (UA) may increase in patients with acute leukemia who undergo their induction chemotherapy, owing to the breakdown of tumor cells. The crystallization of UA or calcium phosphate in renal tubules can result in acute tumor lysis syndrome (ATLS). Some reports indicate that patients who experience ATLS have a better prognosis than those who do not. We investigated the relationship between urinary IP and UA excretion and treatment outcome in children with acute leukemia. Participants included 93 patients with ALL and 31 patients with AML. Urine samples were collected and measured for the first 3 days of induction chemotherapy. Among patients with ALL, urinary IP excretion was significantly higher in patients without relapse than in those with relapse and correlated with long-term outcome. Among patients with AML, urinary IP excretion was significantly higher in patients without induction failure (IF) than those with IF. We propose that higher urinary IP excretion could be a useful prognostic marker for determining favorable outcomes in patients with acute leukemia.

The role of salt abuse on risk for hypercalciuria

BackgroundElevated sodium excretion in urine resulting from excessive sodium intake can lead to hypercalciuria and contribute to the formation of urinary stones. The aim of this study was to evaluate salt intake in patients with urinary lithiasis and idiopathic hypercalciuria (IH).MethodsBetween August 2007 and June 2008, 105 lithiasic patients were distributed into 2 groups: Group 1 (n = 55): patients with IH (urinary calcium excretion > 250 mg in women and 300 mg in men with normal serum calcium); Group 2 (n = 50): normocalciuric patients (NC). Inclusion criteria were: age over 18 years, normal renal function (creatinine clearance ≥ 60 ml/min), absent proteinuria and negative urinary culture. Pregnant women, patients with intestinal pathologies, chronic diarrhea or using corticoids were excluded. The protocol of metabolic investigation was based on non-consecutive collection of two 24-hour samples for dosages of: calcium, sodium, uric acid, citrate, oxalate, magnesium and urinary volume. Food intake was evaluated by the three-day dietary record quantitative method, and the Body Mass Index (BMI) was calculated and classified according to the World Health Organization (WHO). Sodium intake was evaluated based on 24-hour urinary sodium excretion.ResultsThe distribution in both groups as regards mean age (42.11 ± 10.61 vs. 46.14 ± 11.52), weight (77.14 ± 16.03 vs. 75.99 ± 15.80), height (1.64 ± 0.10 vs. 1.64 ± plusorminus 0.08) and BMI (28.78 ± 5.81 vs. 28.07 ± 5.27) was homogeneous. Urinary excretion of calcium (433.33 ± 141.92 vs. 188.93 ± 53.09), sodium (280.08 ± 100.94 vs. 200.44.93 ± 65.81), uric acid (880.63 ± 281.50 vs. 646.74 ± 182.76) and magnesium (88.78 ± 37.53 vs. 64.34 ± 31.84) was significantly higher in the IH group (p < 0.05). There was no statistical difference in calcium intake between the groups, and there was significantly higher salt intake in patients with IH than in NC.ConclusionsThis study showed that salt intake was higher in patients with IH as compared to NC.

Febuxostat: A novel agent for management of Hyperuricemia in gout

Gout is a metabolic disorder characterized by elevated uric acid levels in the body, associated with painful arthritis, tophi and nephropathy. The most frequently used pharmacologic urate lowering strategies involve reducing urate production with a xanthine oxidase inhibitor and enhancing urinary excretion of uric acid with a uricosuric agent. Urate lowering agents are limited in number, availability and effectiveness. The emergence of a new medication, febuxostat, to lower serum urate levels is welcome as no new drug have been approved since the introduction of allopurinol, in 1964, and the drugs that are available have limitations owing to inefficacy or toxicity. Febuxostat is a novel, nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.