Normal Serum Uric Acid Levels Research Articles

Uric Acid Levels During Acute Gout Attacks

We know that a normal serum uric acid level does not exclude gout as the cause of an acutely inflamed joint. But how commonly is the uric acid level

Frequency, Risk, and Cost of Gout-related Episodes Among the Elderly: Does Serum Uric Acid Level Matter?

We examined the association between serum uric acid (SUA) level and the frequency, risk, and cost of gout flares among the elderly. Data were extracted from the Integrated Healthcare Information Services claims database (1999-2005). Patients were included if they had gout, were aged 65 years and older and had both medical and pharmacy benefits, and electronic laboratory data. Patients with gout and gouty episodes were identified using algorithms based on ICD-9-CM codes and medications. Logistic regression and negative binomial regressions were used to study the relationship between SUA concentration and the annual frequency and one-year risk of gout episodes. Generalized linear models were used to examine the direct healthcare costs associated with gout episodes in the 30 days following each episode. Elderly patients with gout (n = 2237) with high (6-8.99 mg/dl) and very high (> 9 mg/dl) SUA concentrations were more likely to develop a flare within 12 months compared to patients with normal (< 6 mg/dl) SUA levels (OR 2.1, 95% CI 1.7-2.6; OR 3.4, 95% CI 2.6-4.4, respectively). In multivariate regressions, the average annual number of flares increased by 11.9% (p < 0.001) with each unit-increase in SUA level above 6 mg/dl (p < 0.001). Among patients with very high SUA levels, average adjusted total healthcare and gout-related costs per episode were $2,555 and $356 higher, respectively, than those of patients with normal SUA levels (both p < 0.001). Higher SUA levels are associated with increased frequency and risk of gout episode, and with higher total and gout-related direct healthcare costs per episode.

A role of IgM antibodies in monosodium urate crystal formation and associated adjuvanticity (135.71)

Abstract Uric acid is a product of purine metabolism that is secreted from injured or dying cells and can act as an endogenous adjuvant. However, uric acid must crystallize to monosodium urate (MSU) before it can activate dendritic cells and cause gouty inflammation. At normal serum uric acid levels, crystallization of uric acid is not observed in vitro. The crucial question therefore is how the crystals form and cause inflammation. It has been reported that serum from rabbits immunized with MSU, increased uric acid precipitation rates. When C57BL6 or Balb/c mice were immunized with MSU, they produced serum factors which bind to MSU crystals, a phenomenon absent in mu chain deficient IgH (or muMT) mice. These observations show that antibodies may be involved in MSU crystallization. Antibodies produced via B cell hybridomas, were observed to precipitate uric acid in vitro, with the variable region acting as the binding domain. Most importantly, the presence of antibody was instrumental in significantly increasing the basal level of inflammation and mediating the adjuvant effect of uric acid in antigen dependent T cell cytotoxicity in B cell deficient mice. Therefore, we have identified a factor in determining uric acid precipitation and possibly its ability to function as an endogenous adjuvant. This finding suggests a new mechanism of the pathogenesis of gouty arthritis and uric acid induced immune activation.

Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease.

It is unclear whether the presence of kidney disease modifies the associations of uric acid with cardiovascular events and death. In the limited access, public use Atherosclerosis Risk In Communities (ARIC) database, associations of serum uric acid levels with cardiovascular events and death were analysed using a parametric proportional hazards model and the modification of these associations by the presence of CKD was assessed using a likelihood ratio test. Of the 15 366 ARIC participants included in this analysis, 461 had CKD (eGFR <60 ml/min/1.73 m(2)). In both non-CKD and CKD sub-groups, participants with hyperuricaemia (> or = 7 mg/dl in men and > or = 6 mg/dl in women) compared to those with normal serum uric acid levels had higher waist circumference and fasting serum insulin levels. In the entire cohort, in a multivariate parametric proportional hazards model, each mg/dl increase in serum uric acid was associated with an increased hazard of cardiovascular events (HR 1.09, 95% CI 1.05-1.12) and death. A multiplicative interaction term of serum uric acid and CKD when added to the above models was significant (P < 0.001). The likelihood ratio test of the models with and without the interaction term was also significant (P < 0.001). In the non-CKD population, a multivariate analysis after adjusting for comorbidities and metabolic syndrome showed a significant association between hyperuricaemia and mortality (HR 1.18, 95% CI 1.04-1.33) but not for cardiovascular events (HR 1.07, 95% CI 0.96-1.19). In the CKD population, the association was not significant for both mortality and cardiovascular events. We conclude that hyperuricaemia is associated with insulin resistance and mortality in the non-CKD population. The presence of CKD attenuates the associations of uric acid with mortality. Interventional studies are warranted to establish the biological role of hyperuricaemia in mortality in non-CKD and CKD populations.

Rasburicase Effectively Lowers Serum Uric Acid Levels in High Risk, Poor Performance Status Patients with Hematologic Malignancies

Tumor lysis remains a significant cause of morbidity and mortality in patients with highly proliferative hematologic malignancies. Traditionally, intravenous hydration and oral allopurinol have been the mainstays of therapy. However in some patients, hyperuricemia and renal failure still occur. The resultant renal failure precludes the administration of full doses of chemotherapy and results in a poor treatment outcome. Recently we participated in a large phase III randomized trial comparing rasburicase with standard allopurinol therapy. Rasburicase is a recombinant urate oxidase that effectively reduces serum uric acid due to conversion of uric acid into allantoin, a readily excretable and soluble substance. The results of that study are reported in a separate abstract. However while the study was open, we treated 12 extremely high risk, newly diagnosed hematologic malignancy patients who were ineligible for the study with commercially available rasburicase off study. The reasons for study ineligibility were ECOG Performance Status 4 and/or expected survival of less than one month. Other baseline characteristics: Diagnosis: Burkitts ALL: 3, AML: 7, CML-BP: 1, T-ALL: 1; Age: 64 (27–85), Sex: 6M/6F; WBC: 58,000/mm3 (1.6- 245,000); LDH: 2201 U/l (1068- >2500); # of preexisting comorbid medical conditions: 4 (0–7); chemotherapy: hyper-CVAD: 4, standard ara-c based rx: 5, high dose ara-C based rx: 3. Nine patients received one dose of rasburicase (0.2 mg/kg IV), 3 patients required a second dose. The median uric acid levels were: pretreatment : 9.2 mg/dl (2.8–28.6), at 24 hours: <0.2 (0.2–7.5) and at 48 hours: <0.2 (<0.2–4.9). All patients achieved normal serum uric acid level by day 2. The median baseline creatinine was 2.6 mg/dl (0.7 – 5.6); by day seven 10 patients had a serum creatinine less than 2 mg/dl (day 7 median creatinine 0.9, range 0.4–5.5). Four patients achieved CR to chemotherapy, 5 had refractory disease and 3 had induction death. Administration of rasburicase in this extremely high risk group of patients resulted in a rapid decrease in serum uric acid levels. In many patients this allowed for preservation of or improvement in renal function and administration of chemotherapy. Although some patients had a poor outcome due to the aggressive nature of their underlying disease, 4 of 12 patients (33%) attained CR and were able to receive subsequent cycles of intensive chemotherapy without incident.

Serum-synovial gradient data of normouricemic patients with history of gout and acute knee effusion

The etiology of arthritis episodes in normouricemic patients with gout is still unclear. We propose that the fluctuation in synovial urate level, as well as pH, ion strength, albumin, and globulin values relative to serum levels, could be involved in crystal formation. To assess serum-synovial gradient (SSG), the sera and synovial fluid (SF) of six normouricemic patients (men, age 48-79) with a history of gout (American College of Rheumatology criteria) and acute knee effusion were screened for uric acid, pH, osmolality (Osm), P/Ca, albumin, globulin, and SSG. Monosodium urate monohydrate (MSUM) crystals were determined by polarized light (PL). Infectious arthritis was ruled out via Gram staining and synovial fluid culture. Negative X-ray and PL microscopy results excluded chondrocalcinosis. Five patients (1-5) had inflammatory knee effusion (WBC >2,000/mm(3)), and one (patient 6) had noninflammatory knee effusion (600 WBC/mm(3)). MSUM crystals were found in the WBC of patient 1 only. He had tophaceous gout with normal serum uric acid levels and showed significant negative Osm and P and positive Ca SSG. Two crystal negative patients had severe negative pH SSG with alkaline synovial fluid, significant P/Ca SSG, and high positive globulin SSG, while one of them had supersaturated SF uric acid content. The other patients displayed an increased Osm and P/Ca SSG. All SSG values were five to ten times higher than the coefficient of variance for used methods. Noninflammatory SF of patient 6 does not appear to be related to active gout. The data on SSG for MSUM, pH, Osm, Alb/Glob, and P/Ca in normouricemic patients with gout history and acute knee effusion was not homogeneous. We propose that acid-base and ionic-protein gradient may lead to instability of subsaturated urate solution, thereby predisposing to MSUM deposits within synovial membrane and inducing inflammation.

Lone hyperuricemia during pregnancy: Maternal and fetal outcomes

Objective: Study of maternal and fetal consequences of lone hyperuricemia during pregnancy and demonstration that lone hyperuricemia is not a risk factor regarding the onset of preeclampsia. Study design: Retrospective study of two groups of women, one found to have lone hyperuricemia during pregnancy ( n=102) and the others with normal serum uric acid levels ( n=100). Results: The only consequence identified of the lone hyperuricemia was a lower birth weight of children born to mothers found to have lone hyperuricemia for more than 2 weeks ( P<0.05). Conclusions: Lone hyperuricemia is not a risk factor regarding the onset of preeclampsia. It is therefore unnecessary to measure serum uric acid level during a normal pregnancy.

Abnormal serum uric acid levels in children

Measurement of the serum uric acid level, most commonly considered in adult patients, is frequently obtained inadvertently for pediatric patients because it is a standard component of many multichannel chemistry profiles offered by clinical laboratories. Most standard references for normal uric acid values do not take into account the impact of the metabolic changes in children at different ages on the uric acid level. A substantial number of childhood conditions may produce perturbations in the serum uric acid level. Knowledge of normal serum uric acid levels and of the conditions affecting those levels in children enables a more focused pursuit of underlying abnormalities. (J P EDIATR 1996;128:731-41)

Serum uric acid levels in normal pregnancy.

Sixty-four patients were assessed throughout pregnancy to determine normal serum uric acid levels (mean +/- 2SD). Serum uric acid levels increased significantly from early pregnancy levels of 0.13-0.33 nmol/L to levels of 0.18-0.45 mmol/L at full-term (p less than 0.005). Factors implicated in uric acid homeostasis contributing to these changes are discussed.

Therapeutic significance of laboratory results in rheumatic disease

A LTHOUGH clinical examination remains ft the bedrock of diagnosis and assessment of patients with rheumatic disorders, laboratory measures provide useful objective data which may confirm or refute the diagnosis, help to assess disease activity, and determine treatment response. DIAGNOSING RHEUMATIC DISORDERS Useful confirmatory investigations in the rheumatic diseases include a raised serum uric acid level in gout, a positive sheep cell agglutina­ tion test in rheumatoid arthritis (RA), a positive test for antinuclear factor in systemic lupus erythematosus (SLE), and the presence of HLA­ B27 in ankylosing spondylitis (AS). False-posi­ tive test results, however, occur frequently. Inter­ estingly, a negative result may be more helpful than a positive one. A normal serum uric acid level in a patient not receiving a uricosuric drug or allopurinol makes the diagnosis of uric-acid gout very questionable. Similarly, the absence of antinuclear factor is strong evidence against the diagnosis of SLE. Since HLA-B27 is present in 8% of the white population, we may calculate from the known prevalence of AS in the commu­ nity the likelihood of a patient without HLA-B27 having AS. In the group of patients with seronegative spondylarthritis the frequency of HLA-B27 dif­ fers (Fig. I), probably because genes for such diseases as ulcerative colitis and psoriasis predis­ pose to spondylitis.· Some nonspecific investiga­ tions, such as C-reactive protein (CRP), may give helpful diagnostic information. Although the level is raised in many inflammatory pro­ cesses, normal or only slightly elevated levels

Renal handling of uric acid in normal subjects by means of the pyrazinamide and probenecid tests.

Pyrazinamide and probenecid tests were used to study the renal mechanisms for urate excretion in 10 normal subjects in the state of low serum uric acid levels (below 3.5 mg/dl), normal serum urate concentrations (between 3.6 and 6.4 mg/dl) and high serum uric acid levels (above 6.5 mg/dl). Presecretory reabsorption of urate was above 99% in all three conditions of uricemia, indicating that filtered urate is nearly completely reabsorbed in the proximal tubule regardless of serum uric acid concentrations. Urate secretion was significantly higher and postsecretory reabsorption was significantly lower when serum uric acid was raised than when serum urate levels were normal or low. The findings indicate that both urate secretion and postsecretory reabsorption play a role in urate homeostasis in states of hyperuricemia.

An evaluation of serum uric acid estimations in toxaemia of pregnancy.

Summary1. There was an increase in the proportion of patients with raised serum uric acid (SUA) levels with increasing severity of pre‐eclamptic toxaemia.2. Raised SUA levels were also found in one‐third of patients with unclassified toxaemia. The criteria of diagnosis of unclassified toxaemia requires revision.3. In the hypertensive patients in this study, the frequency of multiple pregnancy was twice that expected in normal pregnancy.4. The ratio SUA/BUN x 100 was similar in pre‐eclampsia of all three grades of severity and in unclassified toxaemia, but the ratio in essential hypertension in this study was lower than in the other groups. Therefore this ratio may be of value in separating the patients with essential hypertension from the unclassified toxaemia patients.5. While an elevated SUA from 6.0‐10.0 mg./100 ml. was suggestive of preeclampsia, and an increasing level was highly significant, half the patients with pre‐eclampsia had normal SUA levels.6. There is a place for SUA estimations in the management of hypertension in pregnancy, but the results require to be interpreted in the light of clinical findings. patients under their care. Special thanks are due to Professor L. W. Cox for his interest in this study, and to Dr. J. R. Lawrence, for helpful criticism.

Calcific Tendinitis and Soft-Tissue Calcification Resembling Gout

Eight cases have been evaluated in which calcific tendinitis presented as acute monarticular arthritis closely resembling acute gout. In each, soft-tissue calcification in the area of maximum tenderness was demonstrated. All had normal serum uric acid levels. Five of the individuals responded dramatically to colchicine therapy; the other three improved following treatment with phenylbutazone or oxyphenylbutazone. Another patient with uremia, who was undergoing hemodialysis, had extensive soft-tissue calcifications associated with acute inflammation also responsive to colchicine. The calcified material in this patient and in one of the patients with calcific tendinitis was found to be hydroxyapatite.

Serum Uric Acid and Obesity in Hawaiians

HYPERURICEMIA in the Maori of New Zealand has been described. Obesity, diabetes, and ischemic heart disease were also noted to be very prevalent in these Polynesian people.1Another Polynesian group, the Hawaiians, also have a high rate of obesity,2ischemic heart disease,3and diabetes.4In view of the reported relation of hyperuricemia to obesity,5ischemic heart disease,6and diabetes,7it was thought that the Hawaiians would show elevated uric acid levels similar to the Maori. This study reports the finding of a normal mean serum uric acid (SUA) level in a group of Hawaiian men. Body build and serum lipids were also measured and are discussed in relation to the uric acid. Materials and Methods The sample consisted of 49 pure Hawaiian, adult men. It was limited to adult men to avoid the known variations in SUA levels related to puberty and menopause.