Rise In Serum Uric Acid Research Articles

The association between the thyroid feedback quantile-based index and serum uric acid in U.S. adults

ObjectivesPrevious studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form.Research design and methodsThis is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQIFT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQIFT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings.ResultsHigher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a segmented relationship between TT3RI and serum uric acid changes. The saturation and threshold analyses indicated that 18.85 was the turning point (logarithmic likelihood ratio test = 0.036). When TT3RI < 18.85, the relationship between serum uric acid and TT3RI was not significant [β(95% CI) 0.47 (− 0.05, 1.00), P = 0.077], but when TT3RI > 18.85, there was a significant rise in serum uric acid with an increase in TT3RI [β(95% CI) 3.94 (0.94, 6.95), P = 0.010]. A further finding of the interaction test was that impaired thyroid hormone sensitivity and uric acid changes vary among different age groups and BMI levels.ConclusionsDecreased sensitivity to thyroid hormones was associated with high levels of serum uric acid in people with normal thyroid function. The interaction test shows that different age groups and BMI groups impact the association between impaired thyroid hormone sensitivity and serum uric acid. Furthermore, smooth curve fitting revealed a segmental relationship between TT3RI and serum uric acid levels.

#6562 ITGAM PROMOTES MACROPHAGE ALTERNATIVE ACTIVATION IN HYPERURICEMIA-RELATED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD progression is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney injury, repair, and fibrosis. Here, we aim to investigate whether and how macrophage ITGAM contributes to hyperuricemia-related CKD. Method In vivo, we explored dynamic characteristics of renal tissue in hyperuricemia-related CKD. By incorporating mRNA and protein sequencing data, we analyzed gene expression profile, hub genes and potential pathways responsible for disease development, which was further confirmed using qPCR, western blotting, and immunofluorescent stainings. In vitro, we validated bioinformatic findings under different conditions of macrophages with interventions corresponding to core nodes in pathway. Results Hyperuricemia-related CKD was characterized by the rise in serum uric acid, decline in renal function, macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed ITGAM as the potential core gene mediating disease progression which was associated with FAK/Akt1/β-catenin signaling. Notably, we confirmed the upregulated macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys and Raw 264.7 macrophages. In vitro, we verified ITGAM/FAK/Akt1/β-catenin pathway participated in promoting macrophage M2 polarization through silencing Itgam and inhibiting FAK or Akt1 phosphorylation, where the expression of M2 phenotype macrophage markers and downstream molecules in pathway were down-regulated. Conclusion In hyperuricemia-related CKD, ITGAM promotes macrophage M2 polarization contributing to renal fibrosis through FAK/Akt1/β-catenin signaling pathway. Targeting macrophage ITGAM might be a promising therapeutic approach for preventing or delaying CKD.

A CROSS SECTIONAL STUDY OF ASSOCIATION BETWEEN SERUM URIC ACID AND LIPID PROFILE

Background: The association of Serum Uric Acid (SUA) with Lipid Prole is not well studied or little is known so far, although the link between elevated uric acid and metabolic syndrome has been reported in some studies. This study was conducted to establish the relationship between SUA and Lipid Prole among the general adults. Methods: 560 blood samples were collected from general adult participants (male, n = 300 &amp; female, n = 260) were analysed for serum lipid prole (TC, TG, HDL and LDL) and SUA levels. The study subjects were divided by quartiles based on SUA levels (Q1: ≤225 μmol/L, Q2: 226–285 μmol/L, Q3: 286–340 μmol/L and Q4: &gt; 340 μmol/L). Linear regression modelling was used to evaluate the relationship between SUA and Lipid levels. Results: The prevalence of hyperuricemia was 9.2% in males and 10.4% in females. The mean level of SUA was signicantly higher in male (317 ± 90 μmol/L) than in the female (255 ± 65 μmol/L) subjects (p &lt; 0.001). An increasing trend for elevated lipid prole was observed in both genders with increasing levels of SUA in the quartiles (p &lt; 0.05). In regression analysis, a signicant positive correlation was found between SUA and TG, TC and LDL (p &lt; 0.01) while an inverse correlation was observed between SUA and HDL (p &lt; 0.01). After adjusting for potential confounders, lipid prole was linearly associated with SUA levels (p &lt; 0.01 for trend). Conclusions: Lipid parameters (TG, TC, and LDL levels) increases with increase in SUA, whereas HDL decreases with rise in SUA. Cardiovascular risks may be reduced by early prevention of hyperuricemia and dyslipidaemias.

Alleviating Effects of Vitamins C and E Supplementation on Oxidative Stress, Hematobiochemical, and Histopathological Alterations Caused by Copper Toxicity in Broiler Chickens.

Simple SummaryExcessive copper in diets is associated with numerous disadvantageous impacts on poultry. The current study evaluated the efficacy of vitamin C and vitamin E in mitigating oxidative stress, hematobiochemical, and histopathological changes in the kidney induced by copper sulfate (CuSO4) toxicity in broiler chickens. The birds were assigned to five experimental groups: 1st group—basal diet with no additives (control group), 2nd group—basal diet complemented with CuSO4 (300 mg/kg diet), 3rd group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet), 4th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin E (250 mg/kg diet), and 5th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet) + vitamin E (250 mg/kg diet). The current study’s findings showed the possible preventive impacts of dietary antioxidants on hematobiochemical alterations, oxidative stress, and kidney damage induced by CuSO4 toxicity.The current investigation evaluated the alleviating effects of vitamin C and vitamin E on oxidative stress, hematobiochemical, and histopathological changes in the kidney induced by copper sulfate (CuSO4) toxicity in chickens. Two hundred and fifty-one-day-old male broiler chicks were randomly allotted into five experimental groups (five replicates/group, ten chicks/replicate): 1st group—basal diet with no additives (control group), 2nd group—basal diet complemented with CuSO4 (300 mg/kg diet), 3rd group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet), 4th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin E (250 mg/kg diet), and 5th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet) + vitamin E (250 mg/kg diet) for a 42 day feeding period. The results showed a significant reduction in red blood cells (RBCs), hemoglobin (Hb) concentration, and hematocrit values as well as total leukocyte counts (WBCs), lymphocyte, heterophil, and monocyte counts in the CuSO4-intoxicated birds (2.42 × 106/µL, 9.54 g/dL, 26.02%, 15.80 × 103/µL, 7.86 × 103/µL, 5.26 × 103/µL, and 1.18 × 103/µL, respectively, at the 6th week) compared to (2.79 × 106/µL, 10.98 g/dL, 28.46%, 21.07 × 103/µL, 10.84 × 103/µL, 7.12 × 103/µL, and 1.60 × 103/µL, respectively) in the control group. Moreover, CuSO4-intoxicated birds showed hypoglycemia with a rise in serum uric acid and creatinine levels (122.68, 5.18, and 0.78 mg/dL at the 6th week) compared to (159.46, 4.41, and 0.61 mg/dL) in the control group. The CuSO4 toxicity in birds induced oxidative stress, indicated by a high serum malondialdehyde level (MDA) and diminished activity of the antioxidant enzymes (glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) (2.01 nmol/mL, 37.66 U/mL, and 2.91 U/mL, respectively, at the 6th week) compared to (1.34 nmol/mL, 57.00 U/mL, 4.99 U/mL, respectively) in the control group. High doses of Cu exposure caused severe microscopic alterations in kidney architecture. The addition of vitamins C and E, singularly or in combination, displayed a beneficial effect in alleviating these harmful effects of Cu toxicity. These findings showed the possible mitigating impacts of dietary antioxidants on the hematobiochemical alterations, oxidative stress, and kidney damage induced by CuSO4 toxicity.

Fructose tolerance test in obese people with and without type 2 diabetes

Fructose is distinct among common sugars in its ability to raise serum uric acid, and some studies suggest fructose-induced uric acid production may have a role in the ability of this sugar to induce metabolic syndrome. A fructose tolerance test has been previously developed to evaluate the relative ability of fructose to raise uric acid in individuals. However, the effect of fructose to raise uric acid in people with diabetes has not been studied. People with type 2 diabetes (n = 143) and without diabetes controls (n = 132) with similar body mass index (BMI) underwent an oral fructose tolerance test. As a comparison, participants also had their uric acid levels measured after an oral glucose tolerance test on a different day. Serum uric acid was lower in people with type 2 diabetes compared to controls with a similar BMI, especially those with poor glucose control (glycosylated hemoglobin [HbA1c] ≥ 8%). Fructose administration raised serum uric acid in both groups, with a lower absolute rise in people with diabetes. People with diabetes with a blunted rise in serum uric acid had higher baseline serum uric acid concentrations and a higher BMI. People without diabetes with a higher BMI also showed a blunted serum uric acid response. Oral glucose administration lowered serum uric acid in both participants, with a greater fall in those with diabetes. Both the presence of diabetes and obesity blunt the serum uric acid response to fructose ingestion. These data demonstrate altered fructose-dependent urate metabolism in type 2 diabetes.

Studies on antioxidant, hepatoprotective, and vasculoprotective potential of Viola odorata and Wrightia tinctoria.

We have reported the antidyslipidemic, antihypertensive, and Ca++ channel blocking activities of Viola odorata (VO) and Wrightia tinctoria (WT). This study extends our understanding of their therapeutic potential by exploring the effects on biomarkers of hepatic and vascular dysfunction together with phytochemical standardization and antioxidant potential. Total phenolic compounds, total flavonoids content, and proanthocyanins of the methanolic extracts were identified using HPLC. Antioxidant capacity was measured using the in vitro assays. Two studies of 6-week duration were conducted on a high-fat diet rat model to test the leaves and seed extracts of VO and WT (300 and 600mg/kg) for their effect on biomarkers for hepatic and vascular dysfunction. The HPLC analysis showed high contents of total phenolic compounds, total flavonoids content, and proanthocyanins along with distinctive phenolic composition. Both extracts exhibited significant antioxidant potential in 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), fluorescence recovery after photobleaching, and total antioxidant capacity (TAC) assays, comparable with synthetic standard antioxidants. The in vivo studies indicated a significant reduction in the high-fat-diet-induced rise in serum uric acid, phosphorus, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. This study indicates the potential of VO and WT to protect from vascular and hepatic damage and an antioxidant effect, thus making these herbs strong candidates for managing cardiometabolic disorders.

Effects of Serum Uric Acid on Estimated GFR in Cardiac Surgery Patients: A Pilot Study

Background: The aim of the study was to investigate the effects of serum uric acid (SUA) on acute kidney injury (AKI) in patients undergoing cardiac surgery. Methods: Prospectively collected data from a previous study were analyzed to investigate the relationship between SUA and AKI as assessed by neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine (SCr) and kinetic estimated glomerular filtration rate (KeGFR). Results: Patients undergoing cardiovascular surgery (n = 37) were included. SUA was measured at postoperative 1 h. Statistically significant correlations were present between SUA and NGAL measured at postoperative 1 h (r = 0.39, p = 0.008), 6 h (r = 0.31, p = 0.029) and 24 h (r = 0.31, p < 0.001), respectively. Significant correlations were also noted between SUA and SCr measured on postoperative day 1 (r = 0.41, p = 0.006), day 2 (r = 0.29, p = 0.042) and day 3 (r = 0.42, p = 0.009). Negative correlations were demonstrated between SUA and day 1 (r = -0.44, p = 0.007), day 2 (r = -0.43, p = 0.007), day 3 (r = -0.44, p = 0.006 and day 4 KeGFR (r = -0.35, p = 0.035). The inverse relationship of SUA and KeGFR was also demonstrated with a different method (Jelliffe) of measurement. Conclusions: A reduction in glomerular filtration rate (GFR) can lead to a rise in SUA. However, in this study, we are able to show that SUA at 1 h (maximal dilution time) effectively predicts subsequent changes in urinary NGAL, SCr, KeGFR, and the development of AKI. Thus, these findings suggest that uric acid precedes and predicts acute changes in renal function and cannot be ascribed to a simple relationship in which a reduced GFR raises SUA.

Causal or Noncausal Relationship of Uric Acid With Diabetes.

Humans and great apes have higher serum uric acid due to mutations that reduced activity and then silenced the uricase gene about 15 million years ago (1). Uricase degrades intracellular urate in the liver, resulting in low serum uric acid. Parallel silencing of uricase occurred in lesser apes, suggesting natural selection for higher serum uric acid. Uric acid is an antioxidant in the extracellular environment, reacting with superoxide (to make allantoin) and with peroxynitrite (to make triuret). These antioxidant properties of uric acid were proposed to be beneficial by protecting against aging and cancer-associated oxidative stress (2). A different hypothesis has also been proposed (3). The uricase mutation occurred during a period of global cooling that caused seasonal famines for ancestral apes living in Europe due to loss of fruit availability during winter months. The primary food for these ancestral apes was fruit rich in fructose, a nutrient that predisposes to increased hepatic and visceral fat stores and insulin resistance due to its unique metabolism in which transient ATP depletion occurs (4). The nucleotide turnover generates urate intracellularly with a rise in serum uric acid. The intracellular urate causes mitochondrial oxidative stress and inhibits AMPK, resulting in liver fat accumulation, gluconeogenesis, and metabolic syndrome (5,6). Inhibition of uricase amplifies the effects of fructose to induce metabolic syndrome, whereas expressing the ancestral uricase in human liver …

FRI0067 The relationship between fructose intake, alcohol consumption and serum URIC acid levels and the risk of inflammatory polyarthritis. Results from the european prospective investigation of cancer and the norfolk arthritis register: The EPIC-2-noar study

BackgroundIncreased alcohol intake and fructose consumption may be associated with a lower risk of inflammatory arthritis. The mechanism of action may be related to a rise in serum uric acid...

Fructose, uricase, and the Back‐to‐Africa hypothesis

AbstractIn the Middle Miocene (approximately 17 to 12 Ma) at least two radiations of fossil apes from East Africa into Eurasia occurred, and, while controversial, some paleoanthropological studies suggest that one of the Eurasian lineages may have returned to Africa to evolve into humans and the African apes. Here, we present a novel argument supporting this hypothesis. Specifically, the global cooling that occurred in the middle Miocene rendered hominoids living in Europe at risk for starvation as seasonal climate change resulted in less availability of fruits during the winter months. During this time, a mutation in uricase occurred in early hominids that resulted in a rise in serum uric acid. Uric acid has been found to potentiate the effect of fructose to increase fat stores, suggesting that the mutation provided a survival advantage. Such a survival advantage would have been less likely to occur in Africa, where the continued presence of tropical rainforests would have been more likely to provide food throughout the year. Furthermore, Miocene apes in Europe were in protected sites where geographic isolation could have allowed the uricase mutation to be rapidly expressed in the entire population. While speculative, we suggest that the uricase mutation supports an extra‐Africa origin of humans.

Effect of Oral Fructose Load on Serum Uric Acid and Lipids in Kidney Transplant Recipients Treated With Cyclosporine or Tacrolimus

Hyperuricemia, frequently observed following kidney transplantation, may adversely affect graft survival. Although hyperuricemia is a well-known adverse effect of cyclosporine (CsA), a similar effect of tacrolimus (Tac) remains debatable. Hyperuricemia is also seen after oral fructose intake in beverages and processed foods. This sugar is blamed for the epidemic of obesity and metabolic syndrome. The aim of our study was to compare the effects of CsA and Tac on an acute oral fructose load in terms of plasma uric acid, serum lipids, and blood pressure in kidney transplant patients. Thirty-two kidney transplant recipients treated with CsA- or Tac-based triple (calcineurin inhibitor + mycophenolate mofetil + prednisone) immunosuppressive therapy displaying stable allograft function (mean glomerular filtration rate = 53 mL/min/1.73m 2) received an oral challenge with 70 g of fructose. Serum uric acid, lipids, and blood pressure were measured before as well as 60, 120, 180, and 240 minutes after fructose administration. A significant increase in serum uric acid was observed in both groups after oral fructose administration ( P < .001). A peak increase in serum uric acid was recorded at 120 minutes after fructose intake. Serum total, LDL, and HDL cholesterol also significantly decreased and serum triglycerides increased to a similar extent in both CsA and Tac groups. No significant changes in blood pressure were observed after fructose consumption. Oral fructose intake induced an acute rise in serum uric acid and triglycerides and decrease in serum cholesterol among kidney transplant recipients. Those changes were similar among patients treated with CsA or Tac.

Could Uric Acid Have a Role in Acute Renal Failure?

Acute renal failure (ARF), induced by either toxins or ischemia, is associated with significant morbidity. The pathogenesis of ARF is complex and is characterized by renal vasoconstriction and oxidative stress in association with tubular and microvascular injury and interstitial inflammation. In many situations, ARF is associated with a rise in serum uric acid as a result of both increased generation and decreased excretion. Although it is widely recognized that markedly elevated levels of uric acid can cause ARF via supersaturation within the tubules with crystallization and intrarenal obstruction ("acute urate nephropathy"), the possibility that uric acid may affect renal outcomes at concentrations that do not lead to tubular obstruction have not been considered. This article reviews both the salutary and the adverse effects of uric acid on biologic processes and presents the hypothesis that hyperuricemia, particularly if chronic and marked, likely represents a true risk factor for ARF. Hyperuricemia also may account for the paradoxic lack of benefit of diuretics in the management of ARF. It is suggested that studies are needed to investigate the role of chronic hyperuricemia on renal outcomes after acute tubular injury.

The cytoprotective role of a low-molecular-weight heparin fragment studied in an experimental model of glomerulotoxicity

Abnormal glomerular glycosaminoglycan metabolism is involved in the onset of the morphological and functional aberrations of glomerulopathies. In the present study, a heparin derivative, low-molecular-weight heparin, was tested for its ability to afford renoprotection in an established model of experimental glomerulopathy. Two groups of male albino rats of the Wistar strain (140±10 g) received a single intravenous injection of adriamycin (7.5 mg/kg) to induce glomerulopathy, and one of them received low-molecular-weight heparin (Certoparin Sodium, Troparin®; 300 μg/day/rat s.c.) treatment, commencing on day 8, for a week. Urinary protein/creatinine ratio, serum albumin, urea, uric acid and creatinine clearance were evaluated. Renal cell injury was assessed in terms of renal tissue lactate dehydrogenase, aminotransferases (aspartate and alanine transaminases) and alkaline phosphatase activities, as well as renal antioxidant status (superoxide dismutase, catalase and glutathione peroxidase, reduced glutathione, vitamins E and C). The kidney tissue was subjected to histopathologic examination. Low-molecular-weight heparin significantly reduced proteinuria and improved creatinine clearance and serum albumin levels in the rats with glomerulopathy. The significant rise in serum uric acid in the rats with glomerulopathy was reversed by low-molecular-weight heparin. Altered tissue enzyme activities in response to injury, oxidative stress challenged renal antioxidant system and abnormal renal histology were observed in the untreated nephrotic rats, while low-molecular-weight heparin treatment protected the nephrotic rats against these changes. Thus, in this study, low-molecular-weight heparin was evaluated for its role in combating glomerular injury, on the basis of some salient biochemical parameters, oxidative injury indices and histologic picture. The ability of low-molecular-weight heparin to restore glomerular anatamo-functional features in this nephrotoxic condition illuminates its multi-faceted renoprotective role.

Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism.

An elevation in circulating serum uric acid is strongly associated with the development of hypertension and renal disease, but whether uric acid has a causal role or whether it simply indicates patients at risk for these complications remains controversial. We tested the hypothesis that uric acid may have a causal role in the development of hypertension and renal disease by examining the effects of mild hyperuricemia in rats. Mild hyperuricemia was induced in rats by providing a uricase inhibitor (oxonic acid) in the diet. Hyperuricemic rats developed elevated blood pressure after 3 weeks, whereas control rats remained normotensive. The development of hypertension was prevented by concurrent treatment with either a xanthine oxidase inhibitor (allopurinol) or a uricosuric agent (benziodarone), both of which lowered uric acid levels. Blood pressure could also be lowered by reducing uric acid levels with either allopurinol or oxonic acid withdrawal. A direct relationship was found between blood pressure and uric acid (r=0.75, n=69), with a 10-mm Hg blood pressure increase for each 0.03-mmol/L (0.5-mg/dL) incremental rise in serum uric acid. The kidneys were devoid of urate crystals and were normal by light microscopy. However, immunohistochemical stains documented an ischemic type of injury with collagen deposition, macrophage infiltration, and an increase in tubular expression of osteopontin. Hyperuricemic rats also exhibited an increase in juxtaglomerular renin and a decrease in macula densa neuronal NO synthase. Both the renal injury and hypertension were reduced by treatment with enalapril or L-arginine. In conclusion, mild hyperuricemia causes hypertension and renal injury in the rat via a crystal-independent mechanism, with stimulation of the renin-angiotensin system and inhibition of neuronal NO synthase.

Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy

The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjects with early nephropathy. The tolerability of these agents and their effect on the metabolic profile were also evaluated. The study was a one-year prospective, double-blind trial with losartan and enalapril administered alone or in combination with hydrochlorothiazide and other antihypertensive agents. ABP and renal and biochemical parameters were measured at baseline and after 12, 28, and 52 weeks of active treatment. Ninety-two hypertensive type 2 diabetics with early nephropathy completed the study. Both losartan and enalapril administered alone or in combination with other agents induced significant reductions in sitting clinic (P < 0.05) and ABP (P < 0.002) without a statistical difference between groups. Geometric means for urinary albumin excretion (UAE) decreased significantly (P < 0.001) in patients treated with losartan from 64. 1 to 41.5 microg/min and in those treated with enalapril from 73.9 to 33.5 microg/min after 52 weeks of therapy. A significant relationship (P < 0.05) between changes in systolic and diastolic ABP and the decrease in UAE at 52 weeks was seen in both groups. The decline in glomerular filtration rate (GFR) was stabilized at the end of therapy and was identical in both treatment groups. Treatment with enalapril was associated with a significantly higher incidence of cough (P = 0.006) and a rise in serum uric acid (P = 0.002) compared with losartan. Our results indicate that a one-year course of antihypertensive therapy with either losartan or enalapril significantly reduces UAE in hypertensive type 2 diabetic patients with early nephropathy. The reduction in UAE with each treatment is similarly related to decrements in ABP. In addition, the rate of decline in GFR is similar in both treatment groups.

Nephrostomy Failure due to Tumour Lysis Syndrome: Case Reports

Harries S. R. (2000). Clinical Radiology55, 152.

Uric Acid in Pregnancy and Preeclampsia: An Alternative Hypothesis

EDITORIAL COMMENT: This hypothesis that the rise in serum uric acid in patients with preeclampsia is secondary to placental damage rather than alteration in renal function will interest readers. A major problem with the hypothesis is acceptance that raised serum uric acid levels are a feature of normal pregnancy although this was the finding in a careful study recently reported in this Journal (Carter J, Child A. Serum uric acid levels in normal pregnancy. Aust NZ J Obstet Gynaecol 1989; 29: 313–431). This hypothesis could be tested by performing uric acid clearance studies in normal pregnancy and in patients with preeclampsia and relating it to creatinine clearance.

The effects of cimetidine (Tagamet) on renal function in patients with renal failure.

Cimetidine has been administered during 7 days to 28 patients with different degrees of renal failure. Thirteen of these patients had a further week's treatment at least one month later. The daily dose of cimetidine was reduced in relation to pretrial values of creatinine clearance. There was a clear rise in serum creatinine all through the trial (22.3 +/- 2.6% at day 7) (p < 0.001). Maximal decreases in creatinine clearance occurred on day 2 (21.8 +/- 2.2%) and day 3 (23 +/- 2.0%) (p < 0.001), but were still present on days 6 (16.4 +/- 2.9%) and 7 (17.3 +/- 2.8%) (p < 0.001). There was a small rise in serum uric acid all through the trial (p < 0.05). Three days after finished treatment there were no significant differences in serum creatinine, creatinine clearance and serum uric acid when compared to pretrial values. The pattern of changes in serum creatinine and creatinine clearance was the same in both mild and severe renal failure. Glomerular filtration rate determined by |52Cr¿ EDTA clearance before, on day 3 of treatment and 3 days after treatment did not show any differences. No change was seen in serum beta 2-microglobulin during the trial. The decrease in creatinine clearance during treatment with cimetidine is probably not caused by a reduction of glomerular filtration rate, but could be explained by competition by cimetidine for tubular secretion of creatinine. Treatment with cimetidine of patients with renal failure may invalidate measurements of serum creatinine and creatinine clearance as standard routine tests for glomerular filtration rate.

Serum potassium and uric acid changes during treatment with timolol alone and in combination with a diuretic

Timolol, 10 to 40 mg daily, given to 103 patients with uncomplicated arterial hypertension induced significant increments of serum potassium at all dose levels (p less than 0.05). The magnitude of the increments was dependent on daily timolol dosage. When hydrochlorothiazide and amiloride were added, serum potassium decreased (p less than 0.001), but a major determinant of the magnitude of the decrease was the dosage change of the timolol. Serum uric acid was influenced in a paradoxical way during timolol monotherapy; there was a rise in all 3 dosage groups (p less than 0.02) but the lowest group showed the largest increase and vice versa. On addition of hydrochlorothiazide and amiloride, there was a further increase in serum uric acid, the magnitude of which depended on the concomitant reduction in the dose of timolol, with reductions in dose causing a larger rise in serum uric acid and increments, a smaller rise. The increments of serum uric acid were greater in females than in males during both treatment periods. The results indicate that beta blockers induce dose-dependent rises in serum potassium and may counteract undesirable effects of diuretics on serum potassium. Beta blockers seem to have a paradoxical effect on serum uric acid and may aggravate the hyperuricemia induced by diuretics.

Some effects, in man, of varying the load of glucose, sucrose, fructose, or sorbitol on various metabolites in blood

Tolerance tests using glucose, sucrose, fructose, or sorbitol each at 4 dose levels, were carried out in nine healthy young men and during the 90 min after ingestion the plasma serum concentrations of glucose, insulin, fructose, triglyceride, glycerol, uric acid, lactate, and pyruvate were estimated. It was confirmed that serum glucose levels are unaffected by the amount of glucose given. Little fructose seems to be converted to glucose judging by the serum fructose levels following sucrose and fructose, and by the small insulin response to oral fructose. The insulin response to a sucrose meal is half of that after an equivalent amount of glucose. The fall in serum triglyceride seen after carbohydrate meals is not related to insulin. Only glucose is not associated with a rise in serum uric acid, lactate, and pyruvate concentrations after ingestion.