Higher Plasma Uric Acid Levels Research Articles

Uric Acid and Acute Kidney Injury in the Critically Ill

Rationale & ObjectiveUric acid is excreted by the kidney and accumulates in acute kidney injury (AKI). Whether higher plasma uric acid level predisposes to AKI or its complications is not known.Study DesignProspective observational cohort study.Setting & Participants2 independent cohorts of critically ill patients: (1) 208 patients without AKI admitted to the intensive care unit (ICU) at Brigham & Women’s Hospital between October 2008 and December 2016; and (2) 250 participants with AKI requiring renal replacement therapy (RRT) who had not yet initiated RRT enrolled in the Acute Renal Failure Trial Network (ATN) Study.ExposurePlasma uric acid level upon ICU admission and before RRT initiation in the ICU and ATN Study cohorts, respectively.OutcomesIncident AKI and 60-day mortality in the ICU and ATN Study cohorts, respectively.Analytical ApproachLogistic regression models were used to test the association of plasma uric acid level with incident AKI and 60-day mortality.ResultsIn the ICU cohort, median plasma uric acid level was 4.7 (interquartile range [IQR], 3.6-6.4) mg/dL, and 40 patients (19.2%) developed AKI. Higher plasma uric acid levels associated with incident AKI, but this association was confounded by serum creatinine level and was not significant after multivariable adjustment (adjusted OR per doubling of uric acid, 1.50; 95% CI, 0.80-2.81). In the ATN Study cohort, median plasma uric acid level was 11.1 (IQR, 8.6–14.2) mg/dL, and 125 participants (50.0%) died within 60 days. There was no statistically significant association between plasma uric acid levels and 60-day mortality in either unadjusted models or after multivariable adjustment for demographic, severity-of-illness, and kidney-specific covariates (adjusted OR per doubling of uric acid, 1.15; 95% CI, 0.71-1.86).LimitationsHeterogeneity of ICU patients.ConclusionsPlasma uric acid levels upon ICU admission or before RRT initiation are not independently associated with adverse clinical outcomes in critically ill patients.

Plasma Uric Acid (PUA), Renal Hemodynamic Function, and Arterial Stiffness at the Extremes of T1D Duration-Adolescents vs. Adults with T1D for =50 Years

Higher PUA levels are associated with renal vasoconstriction, renin angiotensin aldosterone system (RAAS) activation and vascular stiffness, however the timeline for these associations in T1D is not clear. Our aim was to compare adolescents vs. young adults vs. adults with ≥50 years of T1D from the Canadian Study of Longevity to determine the relationship between PUA and changes in renal hemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of diabetes duration. PUA, GFRinulin, ERPFPAH, vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), plasma renin and aldosterone were measured during a euglycemic clamp in participants with T1D: 27 adolescents (age 16.8±1.9 years), 52 young adults (25.6±5.5 years) and 66 older adults (65.7±7.5 years). PUA levels were highest in the cohort with the longest T1D duration: 197±44 in adolescents vs. 264±82µmol/L in older adults (p<0.001). While PUA levels did not associate with renal hemodynamic parameters in adolescents or young adults, higher PUA correlated with lower GFR in older adults, even after correcting for age, HbA1c and gender (β=-2.12±0.56, p=0.0003). Higher PUA correlated with lower carotid AIx (β=-1.67±0.58, p=0.02) in adolescents, indicating greater compliance. In contrast, PUA correlated with higher cfPWV (less compliance, p=0.03) and higher plasma renin (p=0.03) in adults with ≥50 years of T1D. The relationship between higher PUA with lower GFR, increased arterial stiffness and RAAS activation was observed only in adults with longstanding T1D. T1D may modify the association between PUA, renal hemodynamic function and RAAS activation, leading to renal vasoconstriction and ischemia. Further work is required to determine whether pharmacological PUA lowering prevents injurious hemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes. Disclosure Y. Lytvyn: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc. G. Boulet: Advisory Panel; Self; Medtronic, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Janssen Global Services, LLC., Abbott. M. Farooqi: None. V.S. Lai: None. J.M. Tse: None. L. Cham: None. L. Lovblom: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. E.B. Sochett: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

Plasma Uric Acid and Renal Function in Older Adults with Longstanding Diabetes: Preliminary Analysis from the Canadian Study of Longevity in Type 1 Diabetes

Higher plasma uric acid (PUA) levels, even within the normal range, are associated with lower eGFR and higher blood pressure (BP) in young adults with type 1 diabetes (T1D). To determine if this mechanism is important in longstanding diabetes, we evaluated whether higher PUA levels are associated with similar changes in patients with ≥50 years of T1D.

Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus.

Increased plasma uric acid (PUA) levels are associated with impaired renal function in patients with Type 1 diabetes, but the mechanisms are not well understood. Our aim was to evaluate whether higher PUA levels are associated with increased afferent arteriolar resistance in patients with Type 1 diabetes vs. healthy controls, thereby influencing renal function. PUA, GFR (inulin) and effective renal plasma flow (ERPF; para-aminohippurate) were measured in 70 otherwise healthy patients with Type 1 diabetes and 60 healthy controls. Gomez's equations were used to estimate afferent (RA ) and efferent (RE ) arteriolar resistances, glomerular hydrostatic pressure (PGLO ) and filtration pressure (ΔPF ). The relationships between PUA and glomerular haemodynamic parameters were evaluated by univariable linear regression correlation coefficients. In patients with Type 1 diabetes, higher PUA correlated with lower PGLO (P = 0.002) and ΔPF (P = 0.0007), with higher RA (P = 0.001), but not with RE (P = 0.55). These associations were accompanied by correlations between higher PUA with lower GFR (P = 0.0007), ERPF (P = 0.008), RBF (P = 0.047) and higher RVR (P = 0.021). There were no significant correlations between PUA and renal haemodynamic parameters in the healthy controls. The association between higher PUA with lower GFR and lower ERPF in patients with Type 1 diabetes is driven by alterations in the estimated RA . PUA-mediated RA may be caused by increased tone or thickening of the afferent renal arteriole, which might potentiate renal injury by causing ischaemia to the renal microcirculation.

The Correlation between Clinical Symptoms, Serum Uric Acid Level and EEG in Patient with Bipolar I Disorder

ObjectivesZZHigh uric acid level is related to increased locomotor activities and refractory mood swings. The purpose of this study is to examine the correlation between clinical symptoms of mania, serum uric acid level, and quantitative electroencephalography (QEEG) findings. MethodsZZTwenty-four patients with bipolar disorder and 24 healthy control subjects agreed to participate in the study. When they were hospitalized, the degree of clinical symptoms, uric acid level in blood, and brain QEEG were measured. ResultsZZThe bipolar disorder group showed higher scores on the Young Mania Rating Scale (YMRS ; z=6.02, p<0.05). Patients in their manic episodes showed higher plasma uric acid levels (4.9±1.3 mg/dL) than healthy control subjects (4.2±0.9 mg/dL ; z=2.14, p<0.05). Uric acid levels showed correlation with severity of manic symptoms as assessed using the YMRS in all participants (ρ=0.28, p<0.05). The bipolar disorder group showed decreased relative delta and alpha activity in the fronto-temporo-occipital region compared to the control group (p<0.05). Relative beta in Fp1 (frontopolar), Cz (central mid-line), and Pz (parietal mid-line) and relative gamma in Fp1 were increased in the bipolar disorder group, relative to the control group (p<0.05). The relative beta (ρ=0.47, p<0.05) and gamma (ρ=0.41, p<0.05) in Fp1 electrodes showed positive correlation with the YMRS scores. ConclusionZZAdenosinergic transmission dysfunction may lead to occurrence of manic symptoms, considering that a key role of central nervous system adenosinergic receptors is to inhibit the release of various neurotransmitters and limit neuronal excitability. In addition, QEEG appeared to indicate excitatory neuro-modulation in manic patients.

Plasma uric acid level indicates tubular interstitial leisions at early stage of IgA nephropathy

BackgroundHyperuricemia appeared to be a common symptom in IgA nephropathy (IgAN), even in those with normal eGFR. IgAN was characterized by variation of pathological features, especially variable tubulointerstitial lesions. Since tubular reabsorption and excretion appeared to be more important in determination of plasma uric acid levels in persons without obvious decrease of glomerular filtration rate, we took advantage of our IgAN cohort to investigate whether plasma uric acid level associated with tubular interstitial lesions, and could be considered as a maker for tubular interstitial lesions, especially at early stage with normal eGFR.Methods623 IgAN patients were involved in the present study. Morphological changes were evaluated with Oxford classification scoring system as well as Beijing classification system of IgAN. Statistical analysis was done with SPSS 13.0.ResultsWe found that plasma uric acid level associated with percentage of interstitial fibrosis/tubular atrophy. Higher plasma uric acid levels indicated higher tubulointerstitial scores, either with Oxford system (P = 0.012) or with Beijing classification system (P = 4.8*10-4) in the whole cohort. We also found that in the subgroup of 258 IgAN cases with normal baseline eGFR (eGFR > =90 ml/min/1.73 M2), higher plasma uric acid associated with more severe tubulointerstitial lesions with Beijing scoring system (P = 3.4*10-5). The risk of having more than 10% tubulointerstitial lesions in patients with hyperuricemia increased 58% compared with normal uric acid level. In subgroup with normal eGFR, only hyperuricemia predicted tubulointerstitial leisions, and the risk of having more tubulointerstitial changes increased 100%. Among these patients, hyperuricemia was associated with more tubulointerstitial lesions with a specificity of 60.3%. Specificity increased to 65% among those patients with eGFR > =90 ml/min/1.73 m2.ConclusionsPlasma uric acid levels indicate tubular interstitial lesions in IgAN and hyperuricemia may be considered as a marker for tubulointerstitial lesions.

The effect of albumen removal before incubation (embryonic protein under-nutrition) on the post-hatch performance, regulators of protein translation activation and proteolysis in neonatal broilers

Albumen was removed from broiler eggs before the start of incubation to induce prenatal protein under-nutrition in chicken embryos. With this method, the direct effect of protein deficiency was investigated, differing from mammalian models manipulating the maternal diet where indirect, hormonal effects can interfere. Based on the estimated albumen/egg weight ratio, 10 % of albumen was removed with an 18G needle, after making a hole at the sharp end of the egg with another 18G needle. Eggs were taped thereafter. The sham group underwent the same procedure, except that no albumen was removed. Control eggs did not receive any treatment. The removal of albumen decreased both embryonic and post-hatch body weight up to day 7 compared with the control group. On embryonic day 18, embryos from the albumen-deprived group had higher plasma uric acid levels compared with the sham (P= 0·016) and control (P= 0·009) groups. Moreover, a lower plasma amino acid concentration was observed at hatch compared with the sham (P= 0·038) and control (P= 0·152) groups. These findings indicate an altered protein metabolism. At hatch, a higher mRNA expression of muscle ring finger-1 (MuRF1), a gene related to proteolysis, was observed in albumen-deprived chicks compared with the control and sham chicks, together with an up-regulated expression of atrogin-1 (another atrogene) at this time point in the male protein-deficient chicks. These findings suggest that muscle proteolysis is transiently increased by the removal of albumen before the start of incubation. No evidence was found for altered protein synthesis capacity and translational efficiency in albumen-deprived chicks.

Plasma uric acid levels, uric acid excretion, and response to probenecid in toxemia of pregnancy.

Abstract Women suffering from toxemia of pregnancy were found to have significantly higher plasma uric acid levels and lower urinary uric acid excretion than normal subjects. This was shown to be due to increased tubular reabsorption of uric acid, without signs of other disturbance of renal functions. Probenecid increased the daily excretion of uric acid in the toxemic patients to a much higher degree than in the normals. In the toxemic state the tubular reabsorptive mechanism for uric acid appears to be more sensitive to probenecid than under normal conditions.