allopurinol and Proteinuria

Topics: Adrenal Cortex Hormones; Adult; Allopurinol; Autoimmune Diseases; Azathioprine; Bone Diseases; Diabetes Mellitus; Drug Synergism; Duodenal Ulcer; Embolism, Fat; Glomerulonephritis; Histocompatibility; Humans; Hypertension, Renal; Immunosuppressive Agents; Infections; Kidney Glomerulus; Kidney Transplantation; Malabsorption Syndromes; Male; Mercaptopurine; Neoplasm Transplantation; Neoplasms; Obesity; Osteoporosis; Pancreatitis; Peptic Ulcer Hemorrhage; Phenylbutazone; Postoperative Complications; Proteinuria; Transplantation, Homologous

Topics: Allopurinol; Androstanes; Antineoplastic Agents; Blood Proteins; Cyclophosphamide; Follow-Up Studies; Glucocorticoids; Humans; Melphalan; Plasmacytoma; Prednisone; Proteinuria

Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on renal functions and proteinuria in renal transplant recipients. This study aimed to investigate the effect of allopurinol treatment on renal functions in renal transplant recipients (RTR).. A total of 245 patients with renal transplantation were included in this randomized, placebo-controlled study. Patients were randomized to receive either placebo (121 patients) or 300 mg/day allopurinol (124 patients). We have examined uric acid, urinary protein creatinin ratio, MDRD (the modification of diet in renal diseases) and CRP (C-reactive protein) before and 24 weeks after treatment in both group.. In the allopurinol group, the mean serum uric acid levels, eGFR (estimated glomerular filtration rate), and creatinine urinary albumin creatinin ratio (UACR) significantly improved (p < 0.001). Also uric acid level was positively correlated with the UACR (r = 0,645 p < 0.001) and negatively correlated with MDRD (r = -0,387 p < 0.05) in allopurinol treatment group. A statistically significant increase in CRP level was observed (p < 0,05) in plasebo group. Multivariate regression analysis showed that uric acid was positively correlated with UACR (r = 0,473, β = 0.021, p = 0.002) and negatively correlated with MDRD (r = -0554 β = 0.016, P = 0.001) in allopurinol treatment RTR.. Urate, a salt of uric acid, is lowered by allopurinol treatment resulting in improved eGFR and decreased proteinuria, when compared to the placebo group. Therefore, we suggest that allopurinol therapy should be part of the management of kidney transplant patients with normal kidney function. Long-term follow-up studies will be useful in revealing the effect of uric acid management on kidney functions and proteinuria.

Topics: Allopurinol; C-Reactive Protein; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Proteinuria; Treatment Outcome; Uric Acid

Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease. Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease. We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol might improve endothelial dysfunction, BP, estimated GFR (eGFR), and inflammatory markers.. Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month randomized prospective study. Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups. Flow-mediated dilation (FMD), eGFR, ambulatory BP monitoring, spot urine protein-creatine ratio, and highly sensitive C-reactive protein were measured at baseline and at 4 months.. Age, gender, lipid profile, eGFR, hemoglobin, glucose, and level of proteinuria were similar in hyperuricemic subjects and controls at baseline. As expected, hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients. Allopurinol treatment resulted in a decrease in serum uric acid, a decrease in systolic BP, an increase in FMD, and an increase in eGFR compared with baseline. No significant difference was observed in the control hyperuricemic and normouricemic groups. In a multiple regression analysis, FMD levels were independently related to uric acid both before (beta = -0.55) and after (beta = -0.40) treatment.. Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia.

Topics: Adult; Allopurinol; Analysis of Variance; Asymptomatic Diseases; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Creatinine; Endothelium, Vascular; Female; Glomerular Filtration Rate; Humans; Hyperuricemia; Inflammation Mediators; Kidney; Male; Middle Aged; Prospective Studies; Proteinuria; Regression Analysis; Time Factors; Treatment Outcome; Turkey; Ultrasonography; Uric Acid; Vasodilation

Diabetic nephropathy is the most prevalent cause of end-stage renal disease. Besides factors such as angiotensin II, cytokines, and vascular endothelial growth factor, uric acid may play a role as the underlying cause of diabetic nephropathy. We evaluated allopurinol effects on proteinuria in diabetic patients with nephropathy.. In a double-blinded randomized controlled trial on 40 patients with type 2 diabetes mellitus and diabetic nephropathy (proteinuria, at least 500 mg/24 h and a serum creatinine level less than 3 mg/dL), allopurinol (100 mg/d) was compared with placebo. Administration of antihypertensive and renoprotective drugs (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers continued for both groups, without changes in dosage. Proteinuria was compared at baseline and 2 and 4 months between the two groups.. Each group consisted of 9 men and 11 women. There were no difference between two groups regarding age, body mass index, duration of diabetes mellitus, systolic and diastolic blood pressure, fasting blood glucose, blood urea nitrogen, serum creatinine, serum potassium, and urine volume. Serum levels of uric acid (P = .02) and 24-hour urine protein (P = .049) were significantly lower in the patients on allopurinol, after 4 months of receiving allopurinol, compared with the control group.. Low-dose allopurinol can reduce severity of proteinuria after 4 months of drug administration, which is probably due to decreasing the serum level of uric acid. Thus, allopurinol can be administered as an adjuvant cost-effective therapy for patients with diabetic nephropathy.

Topics: Aged; Allopurinol; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Female; Gout Suppressants; Humans; Male; Middle Aged; Proteinuria

Hyperuricemia is associated strongly with the development of hypertension, renal disease, and progression. Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase. We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients.. We conducted a prospective, randomized, controlled trial of 54 hyperuricemic patients with chronic kidney disease. Patients were randomly assigned to treatment with allopurinol, 100 to 300 mg/d, or to continue the usual therapy for 12 months. Clinical, hematologic, and biochemical parameters were measured at baseline and 3, 6, and 12 months of treatment. We define our study end points as: (1) stable kidney function with less than 40% increase in serum creatinine level, (2) impaired renal function with creatinine level increase greater than 40% of baseline value, (3) initiation of dialysis therapy, and (4) death.. One patient in the treatment group dropped out because of skin allergy to allopurinol. Serum uric acid levels were significantly decreased in subjects treated with allopurinol, from 9.75 +/- 1.18 mg/dL (0.58 +/- 0.07 mmol/L) to 5.88 +/- 1.01 mg/dL (0.35 +/- 0.06 mmol/L; P < 0.001). There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups. There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy, although it did not reach statistical significance (P = 0.08). Overall, 4 of 25 patients (16%) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients (46.1%) in the control group (P = 0.015).. Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease. Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls. Results of this study need to be confirmed with an additional prospective trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease subpopulations.

Topics: Adult; Aged; Allopurinol; Creatinine; Disease Progression; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Hypertension; Hyperuricemia; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Proteinuria; Renal Dialysis; Treatment Outcome; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Child; Child, Preschool; Female; Gas Chromatography-Mass Spectrometry; Gout Suppressants; Humans; Infant; Infant, Newborn; Male; Ornithine Carbamoyltransferase Deficiency Disease; Orotic Acid; Proteinuria; Purine-Pyrimidine Metabolism, Inborn Errors

Topics: Adult; Aged; Enzyme Therapy; Enzymes; Female; Gout; Humans; Liver Function Tests; Male; Middle Aged; Proteinuria; Radiography; Uric Acid; Uricosuric Agents; Xanthine Oxidase

The prevalence of chronic kidney disease (CKD) is increasing worldwide; black patients have an increased risk of developing CKD and end stage kidney disease (ESKD) at significantly higher rates than other races.. A cross sectional study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2020. Demographic and clinical data were extracted from the ongoing kidney outpatient clinic records and interviews, and were filled in a questionnaire. Patients provided blood and urine for laboratory investigations as standard of care, and data were descriptively and inferentially entered into REDcap and analysed using STATA version 17. Multivariable logistic regression analysis was used to identify demographic and clinical variables associated with advanced CKD.. A total of 312 black patients with CKD were enrolled in the study with a median age of 58 (IQR 46-67) years; 58% patients had advanced CKD, 31.5% of whom had grossly increased proteinuria, 96.7% had hypertension, 38.7% had diabetes mellitus and 38.1% had both hypertension and diabetes mellitus. In patients with advanced CKD, the median age was 61 (IQR 51-69) years, eGFR 33 (30-39) mL/min/1.73 m2, serum bicarbonate 22 (IQR 20-24), haemoglobin 12.9 (IQR 11.5-14.0) g/dl and serum uric acid 0.43 (IQR 0.37-0.53). The prevalence of metabolic acidosis was 62.4%, anemia 46.4% and gout 30.9% among those with advanced CKD, while the prevalence of metabolic acidosis and anaemia was 46.6% and 25.9% respectively in those with early CKD. Variables with higher odds for advanced CKD after multivariable logistic regression analysis were hypertension (OR 3.3, 95% CI 1.2-9.2, P = 0.020), diabetes mellitus (OR 1.8, 95% CI 1.1-3.3, P = 0.024), severe proteinuria (OR 3.5, 95% CI 1.9-6.5, P = 0.001), angina (OR 2.5, 95% CI 1.2-5.1, P = 0.008), anaemia (OR 2.9, 95% CI 1.7-4.9, P = 0.001), hyperuricemia (OR 2.4, 95% CI 1.4-4.1, P = 0.001), and metabolic acidosis (OR 2.0, 95% CI 1.2-3.1, P = 0.005). Other associations with advanced CKD were loss of spouse (widow/widower) (OR 3.2, 95% CI 1.4-7.4, P = 0.006), low transferrin (OR 2.4, 95% CI 1.1-5.1, P = 0.028), hyperkalemia (OR 5.4, 95% CI 1.2-24.1, P = 0.029), use of allopurinol (OR 2.4, 95% CI 1.4-4.3, P = 0.005) and doxazosin (OR 1.9, 95% CI 1.2-3.1, P = 0.006).. Hypertension and diabetes mellitus were strongly associated with advanced CKD, suggesting a need for primary and secondary population-based prevention measures. Metabolic acidosis, anemia with low transferrin levels, hyperuricemia and hyperkalemia were highly prevalent in our patients, including those with early CKD, and they were strongly associated with advanced CKD, requiring clinicians and dietitians to be proactive in supporting the needs of CKD patients in meeting their daily dietary requirements towards preventing and slowing the progression of CKD.

Topics: Acidosis; Aged; Allopurinol; Anemia; Bicarbonates; Cross-Sectional Studies; Diabetes Mellitus; Doxazosin; Hemoglobins; Humans; Hyperkalemia; Hypertension; Hyperuricemia; Middle Aged; Prevalence; Proteinuria; Renal Insufficiency, Chronic; South Africa; Tertiary Care Centers; Transferrins; Uric Acid

Hyperuricemia is associated with chronic kidney disease (CKD). Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has a strong effect against hyperuricemia, limited data are available on its renoprotective effect against CKD.. This study was conducted between October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered 40 mg/day of topiroxostat twice daily. All patients were followed for a year. To elucidate the effects of topiroxostat, we evaluated the clinically documented primary indication of progression, viz. laboratory evidence of kidney function decline (reference indicator), uric acid, and hypertension in different patient groups, separated according to their baseline uProt levels and baseline eGFR.. Topiroxostat treatment resulted in significant reduction in SUA (-1.53 mg/dL), systolic blood pressure (-8.9 mmHg), diastolic blood pressure (-5.0 mmHg), and urinary protein excretion (-795.5 mg/gCr) compared with baseline values. However, serum creatinine and urinary NAG levels, and estimated glomerular filtration rate did not change significantly.. Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect in hyperuricemic patients with CKD. Further studies are required to clarify whether topiroxostat prevents the progression of renal disease and improves the prognosis of CKD patients.

Topics: Aged; Biomarkers; Blood Pressure; Enzyme Inhibitors; Female; Humans; Hypertension; Hyperuricemia; Incidence; Japan; Kidney; Male; Middle Aged; Nitriles; Proteinuria; Pyridines; Renal Insufficiency, Chronic; Retrospective Studies; Time Factors; Treatment Outcome; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase

Renal disease is considered the main cause of natural mortality in dogs with canine leishmaniosis. The pathological mechanisms associated with kidney injury in canine leishmaniosis include immune complex glomerulonephritis, tubulointerstitial nephritis and occasionally renal amyloidosis. Proteinuria is a frequent finding in canine leishmaniosis and its quantification by the urine protein-creatinine ratio (UPC) is an important parameter in the staging of canine lesihmaniosis as presented by the LeishVet group.. A 4.5 year-old spayed female Belgian Malinois dog was presented to the Hebrew University Veterinary Teaching hospital with epistaxis and rhinitis and diagnosed also with proteinuria and acute kidney injury (AKI IRIS grade V) associated with canine leishmaniosis that developed to LeishVet stage III with chronic kidney disease (CKD) after stabilization. Clinicopathologic abnormalities included azotemia with a peak creatinine concentration of 7.76 mg/dl (reference interval, 0.3-1.2 ng/dl), hypoalbuminemia (1.76 g/dl, reference interval 3-4.4 g/dl), hyperglobulinemia (4.54 g/dl, reference interval 1.8-3.9 g/dl) and proteinuria (urine protein/creatinine ratio 15.6, normal < 0.2). Serology by the enzyme-linked immunosorbent assay (ELISA) for Leishmania infantum was positive with high antibody levels. The dog was hospitalized and treated with intermittent hemodialysis, feeding through an esophageal feeding tube, medical treatment for protein losing nephropathy and antileishmanial treatment with allopurinol. Kidney function gradually improved and the dog's creatinine levels and proteinuria decreased until complete normalization two years after the acute insult. However, rhinitis and sneezing persisted and although the anti-leishmanial antibodies decreased over time, the dog remains constantly seropositive.. To our knowledge, this is the first report of hemodialysis management of AKI associated with canine leishmaniosis. Hemodialysis was imperative in stabilizing the dog's renal disease and controlling its azotemia. It demostrates that hemodialysis can be beneficial in the management of acute deterioration of kidney disease in canine leishmaniosis.

Topics: Acute Kidney Injury; Allopurinol; Animals; Antiprotozoal Agents; Creatinine; Disease Management; Dog Diseases; Dogs; Epistaxis; Kidney Diseases; Leishmania infantum; Leishmaniasis; Proteinuria; Renal Dialysis

Aortic vascular stiffness has been implicated in the development of cardiovascular disease (CVD) and chronic kidney disease (CKD) in obese individuals. However, the mechanism promoting these adverse effects are unclear. In this context, promotion of obesity through consumption of a western diet (WD) high in fat and fructose leads to excess circulating uric acid. There is accumulating data implicating elevated uric acid in the promotion of CVD and CKD. Accordingly, we hypothesized that xanthine oxidase(XO) inhibition with allopurinol would prevent a rise in vascular stiffness and proteinuria in a translationally relevant model of WD-induced obesity.. Four-week-old C57BL6/J male mice were fed a WD with excess fat (46%) and fructose (17.5%) with or without allopurinol (125mg/L in drinking water) for 16weeks. Aortic endothelial and extracellular matrix/vascular smooth muscle stiffness was evaluated by atomic force microscopy. Aortic XO activity, 3-nitrotyrosine (3-NT) and aortic endothelial sodium channel (EnNaC) expression were evaluated along with aortic expression of inflammatory markers. In the kidney, expression of toll like receptor 4 (TLR4) and fibronectin were assessed along with evaluation of proteinuria.. XO inhibition significantly attenuated WD-induced increases in plasma uric acid, vascular XO activity and oxidative stress, in concert with reductions in proteinuria. Further, XO inhibition prevented WD-induced increases in aortic EnNaC expression and associated endothelial and subendothelial stiffness. XO inhibition also reduced vascular pro-inflammatory and maladaptive immune responses induced by consumption of a WD. XO inhibition also decreased WD-induced increases in renal TLR4 and fibronectin that associated proteinuria.. Consumption of a WD leads to elevations in plasma uric acid, increased vascular XO activity, oxidative stress, vascular stiffness, and proteinuria all of which are attenuated with allopurinol administration.

Topics: Allopurinol; Animals; Diet, Western; Inflammation; Male; Mice; Mice, Inbred C57BL; Proteinuria; Uric Acid; Vascular Stiffness; Xanthine Oxidase

The objective of this study was to evaluate and compare the evolution of the profile currently recommended by the International Renal Interest Society (IRIS) (sCr, UPC and sSDMA) with a panel of other different kidney biomarkers during treatment for canine leishmaniosis. This panel included three urinary glomerular biomarkers (uIgG, uCRP and uferritin) and three urinary tubular biomarkers (uGGT, uNAG and uRBP). These biomarkers were measured in two groups of dogs with canine leishmaniosis at IRIS stage I. Group 1: dogs showing proteinuria (UPC > 0.5) before treatment which did not decrease after treatment; Group 2: dogs showing proteinuria before treatment which decreased after treatment.. Group 1 showed no significant changes in any biomarker after treatment. In group 2, among the biomarkers recommended by the IRIS, only UPC showed a significant decrease after treatment. However all biomarkers of glomerular damage showed a significant decrease after treatment, with uIgG/Cr and uCRP/Cr showing the greater decreases. In addition uRBP/Cr and uNAG/Cr showed significant decreases after treatment.. In dogs with leishmaniosis at IRIS stage I that reduced UPC after treatment, there were no significant changes in serum creatinine and sSDMA. However, all the urine biomarkers evaluated with exception of uGGT showed a significant decrease. These decreases were more evident in those markers related with glomerular function, being uIgG/Cr the biomarker more associated with UPC. Further studies involving a larger number of animals and histological analysis of the kidney would be recommended to confirm these findings and evaluate the routine practical use of these urine biomarkers in canine leishmaniosis.

Topics: Allopurinol; Animals; Antimetabolites; Antiprotozoal Agents; Biomarkers; Dog Diseases; Dogs; Drug Therapy, Combination; Kidney Diseases; Leishmaniasis; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Proteinuria

Topics: Aged; Aged, 80 and over; Drug Substitution; Enzyme Inhibitors; Febuxostat; Female; Gout Suppressants; Humans; Hyperuricemia; Kidney; Male; Middle Aged; Nitriles; Proteinuria; Pyridines; Renal Insufficiency, Chronic; Treatment Outcome; Xanthine Dehydrogenase; Xanthine Oxidase

The aim of the present study was to investigate possible renoprotective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against cisplatin (CIS)-induced acute kidney injury in rats. Male Sprague Dawley rats were randomly assigned into four groups of six rats each, as follows: normal control; CIS, received a single intraperitoneal injection of CIS (7.5 mg/kg); [febuxostat 10 + CIS] and [febuxostat 15 + CIS], received febuxostat (10 and 15 mg/kg/day, respectively, orally) for 14 days, starting 7 days before CIS injection. At the end of experiment, 24-h urine output was collected and serum was separated for biochemical assessments. Kidney tissue homogenate was prepared for determination of oxidative stress-related parameters, nitric oxide (NO), and tumor necrosis factor-α (TNF-α). Moreover, histological alterations of kidney tissues were evaluated. Serum creatinine, blood urea, and urinary total protein were significantly elevated, while serum albumin and creatinine clearance were significantly reduced, in CIS-intoxicated rats, indicating depressed renal function. CIS administration also elicited renal oxidative stress, evidenced by increased malondialdehyde content and depleted levels of reduced glutathione and superoxide dismutase activity. Moreover, enhancement of renal levels of the pro-inflammatory TNF-α indicated renal inflammation. CIS-administered rats also showed increased serum lactate dehydrogenase activity and reduced renal NO bioavailability. Febuxostat dose-dependently improved or restored these changes to near-normal (e.g., mean ± SD of serum creatinine levels in control, CIS, [febuxostat 10 + CIS] and [febuxostat 15 + CIS] groups were 0.78 ± 0.19, 3.28 ± 2.0 (P < 0.01 versus control group), 1.03 ± 0.36 (P < 0.01 versus CIS group), and 0.93 ± 0.21 (P < 0.01 versus CIS group) mg/dl, respectively, and blood urea levels for the different groups were 36.80 ± 4.36, 236.10 ± 89.19 (P < 0.0001 versus control group), 114.50 ± 78.63 (P < 0.05 versus CIS group), and 60.91 ± 14.30 (P < 0.001 versus CIS group) mg/dl, respectively). Histological analysis of renal tissues also demonstrated that febuxostat offered a dose-dependent renoprotection. The present study suggests that antioxidant, anti-inflammatory, and cytoprotective mechanisms potentially mediate the renoprotective effects of febuxostat in CIS-administered rats, presenting febuxostat as a promising combinatorial strategy for cancer patients undergoing CIS chemotherapy.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Cisplatin; Creatinine; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Febuxostat; Glutathione; Inflammation Mediators; Kidney; L-Lactate Dehydrogenase; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Proteinuria; Rats, Sprague-Dawley; Serum Albumin; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Urological Agents; Xanthine Oxidase

Metabolic syndrome (MetS) is a global epidemic associated with great socioeconomic and public health impact. Prevalence of the MetS has been consistently associated with cardiorenal mortality. The objective of this study was to investigate the effect of allopurinol treatment on various components of an established MetS in rats. In a first group, MetS was induced in male Wistar rats by the addition of 10% fructose to drinking water and placing the rats on high-fat and high-salt diet for 12 weeks (M). In the second group, MetS was induced for 12 weeks plus allopurinol administration (20 mg/kg/d) orally for 4 weeks starting at week 9 (MA). The third group was control (C) group that received a normal diet. The M group had higher blood pressure (BP) (85.5 ± 3.17 vs 66.1 ± 3.3 mm Hg) and proteinuria (1.8 ± 0.3 vs 0.59 ± 0.13 g/d) compared with the C group. Allopurinol reversed the BP and proteinuria in MA rats to the control level. Allopurinol administration suppressed the low-grade inflammation associated with MetS and reversed the increases in kidney transforming growth factor beta and urine 8-isoprostane acid observed in the MA group to control levels. In addition, allopurinol reduced angiotensin II and angiotensin receptor type 1 levels in the kidney of MA rats compared with the M group. The administration of allopurinol for short term in an established MetS model reduced features of the MetS especially hypertension and proteinuria. Addition of allopurinol to the therapy of MetS may provide superior means to alleviate hypertension and proteinuria associated with MetS.

Topics: Allopurinol; Animals; Antimetabolites; Blood Pressure; Diet, High-Fat; Disease Models, Animal; Fructose; Hypertension; Kidney; Male; Metabolic Syndrome; Oxidative Stress; Proteinuria; Rats; Rats, Wistar; Renin-Angiotensin System; Sodium Chloride, Dietary; Translational Research, Biomedical

The aim of this study was to evaluate if xanthine oxidase and myeloperoxidase levels quantitation method may alternate routine culture method, which takes more time in the diagnosis of urinary tract infections.. Five hundred and forty-nine outpatients who had admitted to Clinic Microbiology Laboratory were included in the study. The microorganisms were identified by using VITEK System. The urine specimens that were negative from the quantitative urine culture were used as controls. The activities of MPO and XO in spot urine were measured by spectrophotometric method.. Through the urine cultures, 167 bacteria were isolated from 163 urine specimens; 386 cultures yielded no bacterial growth. E. coli was the most frequent pathogen. In infection with E. coli both XO and MPO levels were increased the most. The sensitivity, specificity, positive predictive value, and negative predictive value for XO were 100%, 100%, 100%, and 100%, respectively. These values for MPO were 87%, 100%, 100%, and 94%, respectively.. These data obtained suggest that urine XO and MPO levels may be new markers in the early detection of UTI.

Topics: Adolescent; Adult; Aged; Biomarkers; Child; Child, Preschool; Early Diagnosis; Escherichia coli Infections; Female; Humans; Infant; Male; Middle Aged; Peroxidase; Proteinuria; Sensitivity and Specificity; Urinary Tract Infections; Xanthine Oxidase; Young Adult

Topics: Aged; Allopurinol; Creatinine; Female; Glomerular Filtration Rate; Humans; Hypertension; Hyperuricemia; Male; Middle Aged; Proteinuria; Xanthine Oxidase

The goal of this study was to test the hypothesis that NADPH oxidase contributes importantly to renal cortical oxidative stress and inflammation, as well as renal damage and dysfunction, and increases in arterial pressure. Fifty-four 7- to 8-wk-old Dahl salt-sensitive (S) or R/Rapp strain rats were maintained for 5 wk on a high sodium (8%) or high sodium + apocynin (1.5 mmol/l in drinking water). Arterial and venous catheters were implanted on day 21. By day 35 in the high-Na S rats, mRNA expression of renal cortical gp91phox, p22phox, p47phox, and p67phox NADPH subunits in S rats increased markedly, and treatment of high-Na S rats with the NADPH oxidase inhibitor apocynin resulted in significant decreases in mRNA expression of these NADPH oxidase subunits. At the same time, in apocynin-treated S rats 1) renal cortical GSH/GSSG ratio increased, 2) renal cortical O2(.-) release and NADPH oxidase activity decreased, and 3) renal glomerular and interstitial damage markedly fell. Apocynin also decreased renal cortical monocyte/macrophage infiltration, and apocynin, but not the xanthine oxidase inhibitor allopurinol, attenuated decreases in renal hemodynamics and lowered arterial pressure. These data suggest that NADPH oxidase plays an important role in causing renal cortical oxidative stress and inflammation, which lead to decreases in renal hemodynamics, renal cortical damage, and increases in arterial pressure.

Topics: Acetophenones; Allopurinol; Animals; Blood Pressure; Disease Models, Animal; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; Glomerular Filtration Rate; Glutathione; Glutathione Disulfide; Heart Rate; Hemodynamics; Hypertension; Inflammation; Kidney Cortex; Kidney Diseases; Macrophages; Monocytes; NADPH Oxidases; Oxidative Stress; Protein Subunits; Proteinuria; Rats; Rats, Inbred Dahl; Renal Circulation; RNA, Messenger; Sodium Chloride, Dietary; Superoxides; Time Factors; Xanthine Oxidase

Especially in damaged organs, adequate organ preservation is critically important to maintain viability. Institut Georges Lopez-1 (IGL-1) is a new preservation solution, with an extracellular sodium/potassium ratio and polyethylene glycol as a colloid. The influence of warm and cold ischemia was evaluated in a rat Lewis-Lewis transplant model with a follow up of 14 days. Eight groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0 and 15 min followed by 0- or 24-h cold storage (CS) preservation in IGL-1 or UW-CSS. Blood was collected daily during the first week and at day 14. Recipients were placed in metabolic cages at day 4 and 14 after transplantation allowing urine collection and adequate measurement of glomerular filtration rate. Focussing on inflammation, reactive oxygen species production, proximal tubule damage, proteinuria, histology, and renal function after transplantation we could not show any relevant difference between IGL-1 and UW-CSS. Furthermore, the combination of 15-min warm ischemia and by 24-h cold ischemia did not result in life sustaining kidney function after transplantation, irrespective of the used solution. In the present experiment, static CS preservation of ischemically damaged rat kidneys in either IGL-1 or UW-CSS rendered equal results after transplantation.

Topics: Adenosine; Allopurinol; Animals; Cold Temperature; Glomerular Filtration Rate; Glutathione; Insulin; Ischemia; Kidney; Kidney Transplantation; Kidney Tubules, Proximal; Male; Organ Preservation; Organ Preservation Solutions; Proteinuria; Raffinose; Rats; Rats, Inbred Lew; Reactive Oxygen Species

Exercise-induced proteinuria is a common consequence of physical activity and is caused predominantly by alterations in renal hemodynamics. Although it has been shown that exercise-induced oxidative stress can also contribute to the occurrence of postexercise proteinuria, the sources of reactive oxygen species that promote it are unknown. We investigated the enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase (XO) as possible sources of oxidative stress in postexercise proteinuria. First, we evaluated the effect of blocking the NADPH oxidase enzyme on postexercise proteinuria. We found a significant increase in urinary protein level, kidney thiobarbituric acid-reactive substances (TBARS), and protein carbonyl content after exhaustive exercise, and NADPH oxidase activity was induced by exercise. Rats that were treated with an NADPH oxidase inhibitor for 4 days before exhaustive exercise showed no increase in kidney TBARS or protein carbonyl derivative level and no proteinuria or NADPH oxidase activation. In the next set of experiments, we investigated the effect of XO blockage on postexercise proteinuria. Oxypurinol, an XO inhibitor was administered to rats for 3 days before exercise. Although XO inhibition significantly decreased kidney TBARS levels and protein carbonyl content in exercised rats, the inhibition did not prevent exercise-induced proteinuria. However, plasma and kidney XO activity was not induced by exercise, but rather it was suppressed under oxypurinol treatment. These results suggest that increased NADPH oxidase activity induced by exhaustive exercise is an important source of elevated oxidative, stress during exercise, which contributes to the occurrence of postexercise proteinuria.

Topics: Animals; Enzyme Inhibitors; Female; Kidney; NADPH Oxidases; Oxidative Stress; Oxypurinol; Physical Conditioning, Animal; Protein Carbonylation; Proteinuria; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Chronic hypoxic (CH) preconditioning reduces superoxide-induced renal dysfunction via the upregulation of superoxide dismutase (SOD) activity and contents. Endotoxaemia reduces renal antioxidant status. We hypothesize that CH preconditioning might protect the kidney from subsequent endotoxaemia-induced oxidative injury. Endotoxaemia was induced by intraperitoneal injection of lipopolysaccharide (LPS; 4 mg kg(-1)) in rats kept at sea level (SL) and rats with CH in an altitude chamber (5500 m for 15 h day(-1)) for 4 weeks. LPS enhanced xanthine oxidase (XO) and gp91phox (catalytic subunit of NADPH oxidase) expression associated with burst amount of superoxide production from the SL kidney surface and renal venous blood detected by lucigenin-enhanced chemiluminescence. LPS induced a morphologic-independent renal dysfunction in baseline and acute saline loading stages and increased renal IL-1beta protein and urinary protein concentration in the SL rats. After 4 weeks of induction, CH significantly increased Cu/ZnSOD, MnSOD and catalase expression (16 +/- 17, 128 +/- 35 and 48 +/- 21, respectively) in renal cortex, and depressed renal cortex XO (44 +/- 16%) and renal cortex (20 +/- 9%) and medulla (28 +/- 11%) gp91phox when compared with SL rats. The combined effect of enhanced antioxidant proteins and depressed oxidative proteins significantly reduced LPS-enhanced superoxide production, renal XO and gp91phox expression, renal IL-1beta production, and urinary protein level. CH also ameliorated LPS-induced renal dysfunction in the baseline and acute saline loading periods. We conclude that CH treatment enhances the intrarenal antioxidant/oxidative protein ratio to overcome endotoxaemia-induced reactive oxygen species formation and inflammatory cytokine release.

Topics: Acclimatization; Altitude; Animals; Catalase; Chronic Disease; Disease Models, Animal; Endotoxemia; Female; Glomerular Filtration Rate; Hypoxia; Interleukin-1beta; Kidney; Lipopolysaccharides; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Proteinuria; Rats; Rats, Wistar; Renal Circulation; Sodium Chloride; Superoxide Dismutase; Superoxides; Xanthine Oxidase

Topics: Acclimatization; Altitude; Animals; Catalase; Chronic Disease; Disease Models, Animal; Endotoxemia; Glomerular Filtration Rate; Hypoxia; Interleukin-1beta; Kidney; Lipopolysaccharides; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Proteinuria; Rats; Renal Circulation; Sodium Chloride; Superoxide Dismutase; Superoxides; Xanthine Oxidase

Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on hypertension, renal function, and proteinuria in patients with glomerular filtration rate (GFR) >60 ml/min. We therefore conducted a prospective study to investigate the benefits of allopurinol treatment in hyperuricemic patients with normal renal function.. Forty-eight hyperuricemic and 21 normouricemic patients were included in the study. Hyperuricemic patients received 300 mg/day allopurinol for three months. All patients' serum creatinine level, 24-h urine protein level, glomerular filtration rate, and blood pressure levels were measured at baseline and after three months of treatment.. A total of 59 patients completed the three-month follow-up period of observation. In the allopurinol group, serum uric acid levels, GFR, systolic and diastolic blood pressure, and C-reactive protein (CRP) levels significantly improved (P < 0.05). However, urine protein excretion remained unchanged (P > 0.05). No correlation was observed between changes in GFR and changes in CRP, or blood pressure in the allopurinol group. No significant changes were observed in the control group (P > 0.05).. We bring indirect evidence that hyperuricemia increases blood pressure, and decreases GFR. Hence, management of hyperuricemia may prevent the progression of renal disease, even in patients with normal renal function, suggesting that early treatment with allopurinol should be an important part of the management of chronic kidney disease (CKD) patients. Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and hypertension.

Topics: Aged; Allopurinol; Creatinine; Female; Glomerular Filtration Rate; Humans; Hypertension; Hyperuricemia; Male; Middle Aged; Prospective Studies; Proteinuria; Treatment Outcome

Vascular aging is characterized by endothelial dysfunction that is primarily attributed to increased superoxide production, the exact source of which remains ambiguous. This study compared the NAD(P)H and xanthine oxidase (XO) systems as sources of superoxide and impaired vascular function in aging. Male Sprague Dawley rats, 4-months-old (young) and 18-months-old (Aging), were used. Systolic blood pressure was higher (36 +/- 3%) in the aging group compared with young rats, and this was accompanied by reduced acetylcholine-induced renal vasodilatation. Urinary excretion of nitrite was lower in the aging rats (P < 0.05), and this was associated with reduced nitric oxide synthase (NOS) activity and reduced eNOS and iNOS protein expression in the aorta. Aged rats showed a n approximately twofold increase in free radical generation, as evident by increased plasma 8-isoprostane level, and an approximately fourfold increase in proteinuria compared with the young rats. Vascular NADP(H) oxidase was unchanged between both groups, as was the expression of p67phox or p47phox components of NAD(P)H oxidase. However, XO activity was increased (19 +/- 1%; P < 0.05) as well as XO expression in the aorta of aging rats. These results suggest that increased free radical generation-associated increase in SBP in aging rats is XO but not NAD(P)H oxidase-dependent.

Topics: Acetylcholine; Aging; Animals; Aorta; Blood Pressure; Free Radicals; Male; NADPH Oxidases; Nitric Oxide Synthase; Oxidative Stress; Proteinuria; Rats; Rats, Sprague-Dawley; Xanthine Oxidase

To investigate if increased lipid peroxidation is involved in hypercholesterolemia-induced hypertension and renal injury, we examined the effects of allopurinol, a xanthine oxidase inhibitor, on these conditions. Groups of male Sprague--Dawley rats were fed for 8 weeks with a high-cholesterol diet (4% cholesterol), a high-cholesterol plus allopurinol (10 mg/kgBW/day) diet or a normal diet. Systolic blood pressure (SBP), serum lipids, uric acid (UA) and malondialdehyde (MDA) as a measure of lipid peroxides, and urinary excretion of protein (UP) were measured after 0, 4 and 8 weeks. Urinary excretion of nitrite plus nitrate (UNOx) and iron (UFe), and MDA in the kidney were measured after 8 weeks. The renal injury was evaluated by the glomerular sclerosis score (SS). The high-cholesterol diet increased SBP, serum total cholesterol and UA, MDA in the serum and kidney, UP, UNOx, UFe and SS. Allopurinol ameliorated cholesterol-induced elevation in serum UA, MDA in the serum and kidney, UP, UNOx, UFe and SS, but did not affect SBP. Hence, our results suggest that lipid peroxidation may be involved in hypercholesterolemia-induced renal injury, and that suppression of lipid peroxidation can reduce such injury.

Topics: Allopurinol; Animals; Blood Pressure; Body Weight; Cholesterol; Creatinine; Enzyme Inhibitors; Heart Rate; Hemodynamics; Hypercholesterolemia; Hypertension; Iron; Kidney; Kidney Diseases; Kidney Function Tests; Male; Malondialdehyde; Nitric Oxide; Proteinuria; Rats; Rats, Sprague-Dawley; Triglycerides; Uric Acid; Xanthine Oxidase

Passive Heymann nephritis (PHN) in rats is a model of human membranous nephropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have been implicated in the subsequent glomerular damage which leads to proteinuria. This study examines the involvement of xanthine oxidase in this process. Xanthine oxidase activity was increased nearly twofold in glomeruli isolated 1 and 12 d after induction of PHN, and this was associated with increased glomerular superoxide anion generation. Analysis of glomerular samples by Northern and Western blotting revealed no quantitative changes in xanthine oxidoreductase expression in PHN, suggesting conversion of xanthine dehydrogenase to the oxidase form as the cause of increased activity. Treatment of rats with tungsten, an inhibitor of xanthine oxidase, before induction of PHN resulted in a marked decrease in glomerular xanthine oxidase activity and superoxide anion generation, and decreased proteinuria by 80% (day 12: 423+/-245 mg/d in PHN versus 78+/-53 mg/d in tungsten-treated PHN animals, P < 0.01). These findings point to a pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of importance in the therapy of human membranous nephropathy.

Topics: Animals; Binding Sites; Blotting, Northern; Blotting, Western; Culture Techniques; Disease Models, Animal; Glomerulonephritis; Hemodynamics; Kidney Function Tests; Kidney Glomerulus; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Reference Values; Superoxide Dismutase; Superoxides; Tungsten; Xanthine Oxidase

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, the 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 +/- 6.39 mg/24 h; NCG = 59.8 +/- 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 +/- 17.5 mg/24 h; TNG-I = 49.1 +/- 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 +/- 22.23 mg/24 h and 72.66 +/- 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48%) and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Topics: Allopurinol; Animals; Antineoplastic Agents; Biopsy; Disease Models, Animal; Disease Progression; Doxorubicin; Follow-Up Studies; Free Radical Scavengers; Glomerulosclerosis, Focal Segmental; Kidney Glomerulus; Kidney Tubules; Male; Nephritis, Interstitial; Proteinuria; Random Allocation; Rats; Rats, Wistar; Ultrasonography

Protein restriction ameliorates proteinuria in acute adriamycin (ADR) nephrosis and decreases the renal levels of xanthine oxidase (XO), a putative mediator of ADR nephrotoxicity. Hypothetically, the effect of protein restriction on renal XO levels may be due to variations in plasma and tissue proteic amino acids (AA). To elucidate this point, the levels of AA in plasma and in renal homogenates were determined in rats with ADR nephrosis and fed diets with different protein contents: (a) high (35%) casein; (b) standard (21%) casein; (c) low (9%) casein; (d) low casein plus a synthetic mixture of Val, Leu and Ile. The protein content of the diet determined certain marked variations in plasma AA: high levels of Val, Leu and Ile were found in rats fed on a high protein diet, while the same AA were low, in rats on low protein regimen. Supplementation of the low protein diet with a synthetic mixture of branched-chain AA (Val, Leu and Ile) normalized the plasma levels of these AA. In spite of these changes, tissue AA were similar in all groups, regardless of the protein contents of the diets. Furthermore, the levels of renal XO and proteinuria were unrelated to variations in plasma AA, since both parameters were low in protein-restricted and protein-restricted AA-supplemented rats while high in rats fed a high or normoproteic diet. These data demonstrate that low protein diets induce marked alterations in plasma AA composition which are similar in may respects to those found in protein malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Amino Acids; Animals; Blood Pressure; Dietary Proteins; Doxorubicin; Kidney; Kidney Function Tests; Male; Nephrosis; Proteinuria; Rats; Rats, Inbred Strains; Xanthine Oxidase

Proteinuria and renal xanthine metabolising enzymes, xanthine oxidase and xanthine dehydrogenase, were evaluated in Adriamycin-treated rats fed standard (21% casein) and low-protein (6% casein) diets. In rats fed a standard diet Adriamycin was associated with increased activities in the kidney of xanthine oxidase and xanthine dehydrogenase and induced massive proteinuria. The pharmacological block of both enzymes by allopurinol and tungsten block of both enzymes by allopurinol and tungsten reduced proteinuria to one-third of the original levels. Rats fed a low-protein diet presented decreased levels of renal xanthine oxidase and xanthine dehydrogenase and were only slightly proteinuric. Finally, rats shifted from a low-protein diet to a normal one developed massive proteinuria in spite of normal or slightly decreased levels of renal xanthine oxidase and xanthine dehydrogenase. We conclude that a low-protein diet is effective in decreasing the levels of xanthine metabolising enzymes that are in part responsible for the renal damage due to Adriamycin. This is not however the unique mechanism by which the low-protein diet protects against the development of proteinuria in Adriamycin nephrosis; other factors must also be hypothesised.

Topics: Animals; Dietary Proteins; Disease Models, Animal; Doxorubicin; Male; Nephrosis; Proteinuria; Rats; Rats, Inbred Strains; Xanthine Dehydrogenase; Xanthine Oxidase; Xanthines

The perfused isolated kidney is a partial ischemic system that is characterised by glomerular proteinuria and release of glomerular heparan sulfate. Metabolic changes associated with the levels of glutathione, xanthine oxidase and glyceraldehyde 3-dehydrogenase indicated that oxygen radical metabolites were being produced during the perfusion. We have demonstrated that a mixture of oxygen metabolite scavengers containing mannitol, superoxide dismutase and catalase included in the perfusion medium significantly reduced protein excretion. Similar results were obtained with the administration of allopurinol to the rat 24h prior to kidney removal and allopurinol in the perfusion medium. [35S]Heparan sulfate loss from the glomerulus was totally inhibited by the scavenger mixture. These results suggest that reactive oxygen metabolites may be involved in damage to renal capillaries, specifically to heparan sulfate proteoglycan, which leads to proteinuria as a result of partial ischemia produced during perfusion.

Topics: Animals; Catalase; Free Radicals; Glutathione; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycosaminoglycans; Heparitin Sulfate; Kidney Glomerulus; Male; Mannitol; Oxygen; Perfusion; Proteinuria; Rats; Rats, Inbred Strains; Superoxide Dismutase; Xanthine Oxidase

1. The hypothesis was tested that the renal xanthine oxidase system provides a source of oxygen free radicals in puromycin aminonucleoside and adriamycin experimental nephrosis by generating uric acid from hypoxanthine and xanthine. 2. The concentrations in renal tissue of the putative intermediary products of puromycin aminonucleoside metabolism, hypoxanthine and xanthine, and of their precursors, adenosine and inosine, were lower in rats treated with puromycin aminonucleoside than in normal controls, whereas concentrations of the metabolites were normal after adriamycin intoxication. Their daily urinary excretion was lower in the 24 h after puromycin aminonucleoside administration compared with the baseline values and returned to near normal levels within 5 days. After adriamycin the 24 h urinary excretion of xanthine and uric acid was double the baseline levels (P less than 0.001). 3. When equimolar amounts of hypoxanthine were injected instead of puromycin aminonucleoside, the concentration of all bases increased slightly in renal tissue and their urinary efflux was double the baseline level: allantoin, uric acid, the unmodified nucleotide and xanthine were the most represented compounds in urine. 4. The enzymatic activities relative to xanthine oxidase (EC 1.1.3.22) and xanthine dehydrogenase (EC 1.1.1.204) in renal tissues were unchanged 1 day after puromycin aminonucleoside or hypoxanthine intoxication and only moderately increased in both groups at 13 days (the time of appearance of heavy proteinuria in the puromycin aminonucleoside-treated group). In contrast, xanthine oxidase and xanthine dehydrogenase activities were higher in adriamycin-treated rats at 1 and 15 days after the treatment (P less than 0.001). 5. Feeding rats with normoprotein diets containing tungsten induced a marked and constant decrease of renal xanthine oxidase and xanthine dehydrogenase activities to 20% of the baseline values in both puromycin aminonucleoside- and adriamycin-treated rats. Inhibition of renal xanthine oxidase and xanthine dehydrogenase activities by tungsten was associated with a marked reduction (P less than 0.001) of proteinuria in adriamycin-treated rats and the same occurred with allopurinol, a specific inhibitor of xanthine oxidase activity. In contrast, tungsten treatment did not reduce the proteinuria associated with puromycin aminonucleoside, which reached a maximum 13 days after puromycin aminonucleoside intoxication. Hypoxanthine-treated rats were

Topics: Allantoin; Animals; Doxorubicin; Hypoxanthines; Kidney; Male; Nephrosis; Proteinuria; Purines; Puromycin Aminonucleoside; Rats; Rats, Inbred Strains; Time Factors; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase; Xanthines

1. A low protein diet prevents the development of proteinuria and glomerular damage in adriamycin experimental nephrosis without affecting renal haemodynamics. In this study the hypothesis was tested as to whether protein restriction is able to modulate the purine metabolic cycle and related enzymes such as xanthine oxidase, one of the putative effectors of adriamycin nephrotoxicity. 2. Renal activities of xanthine oxidase and purine nucleoside phosphorylase were markedly depressed in adriamycin-treated rats fed a 9% casein (low protein) diet compared with the group fed a 22% casein (normal protein) diet both 1 day after adriamycin administration and at the time of appearance of heavy proteinuria (day 15), whereas the activity of renal adenosine deaminase was unchanged. 3. The concentrations of the metabolic substrates of xanthine oxidase, i.e. hypoxanthine and xanthine, were constantly lower in renal homogenates of rats fed a low protein diet compared with those on a normal protein diet. In urine, uric acid, the product of hypoxanthine-xanthine transformation, was lower 1 day after adriamycin injection in protein-restricted rats compared with the group on a normal protein diet which showed a marked increase in its excretion. At the same time, the urinary efflux of adenosine 5'-monophosphate, which is the precursor nucleotide of the above-mentioned nucleosides and bases, was very high in rats fed a low protein diet, whereas it was absent in the group on a normal protein diet. 4. The progressive increment in proteinuria of glomerular origin (i.e. increased excretion of albumin and transferrin) typical of adriamycin-treated rats fed a normal protein diet was inhibited in the protein-restricted animals, which were normoproteinuric on day 10 and were only slightly proteinuric on day 15. 5. Like protein restriction, the pharmacological suppression of renal xanthine oxidase by dietary tungstate and the scavenging by dimethylthiourea of the putative free radical deriving from the action of xanthine oxidase, were associated with a similar (quantitative and qualitative) inhibition of glomerular proteinuria. 6. These data demonstrate that dietary protein restriction is associated with a block in purine metabolism within the kidney due to a marked reduction in the activities of two main enzymes of the cycle, i.e. purine nucleoside phosphorylase and xanthine oxidase, the latter being a putative effector of adriamycin nephrotoxicity. The partial reduction of proteinur

Topics: Animals; Dietary Proteins; Disease Models, Animal; Doxorubicin; Kidney; Male; Nephrosis; Protein Deficiency; Proteinuria; Purine-Nucleoside Phosphorylase; Purines; Rats; Rats, Inbred Strains; Xanthine Oxidase

We examined how a combination of pharmacologic agents ("rescue" agents) affect the function of hypothermically preserved dog kidneys at the time of reperfusion. Dog kidneys were preserved either by simple cold storage in EuroCollins' solution for 24 or 48 hours or by continuous perfusion at 5 degrees C in Belzer's gluconate-hydroxyethyl starch solution for as long as 5 days. After preservation, renal functions were measured with the isolated perfused kidney model. Kidneys were reperfused at normothermia either with or without the addition of a combination of rescue agents to the reperfusion medium. The rescue agents studied were allopurinol (1 mmol/L); superoxide dismutase (32,000 U/L); catalase (137,500 U/L); dimethylthiourea (3 mmol/L); glutathione (3 mmol/L); desferrioxamine (0.2 gm/L), for protection against O2 free radical injury and lipid peroxidation injury; verapamil (25 mg/L), as a Ca channel blocker; and ATP-MgCl2 (0.3 mmol/L), to stimulate energy metabolism. The renal functions we measured were glomerular filtration rate (GFR) (creatinine clearance), urine production, perfusate flow, urinary protein concentration, Na reabsorptive capacity, and tissue concentrations of ATP, K, and total tissue water. GFR was reduced by 75% to 90% after all periods of preservation, and the rescue agents had no effect on GFR. Sodium reabsorption was reduced from 98% to a range of 40% to 50% after 48 hours of cold storage or 5 days of machine perfusion and was not increased by rescue agents. There was a time-dependent increase in the amount of urine protein that was not affected by rescue agents. The addition of rescue agents did not affect total tissue water or concentrations of ATP or K in kidneys after normothermic reperfusion. These results demonstrate that pharmacologic agents previously suggested to suppress reperfusion damage in kidneys are not effective in this model. Therefore it is likely that kidneys damage occurs primarily during preservation, which suggest that optimal function on reperfusion calls for the development of better methods of preservation.

Topics: Allopurinol; Animals; Ca(2+) Mg(2+)-ATPase; Calcium-Transporting ATPases; Catalase; Cold Temperature; Deferoxamine; Dogs; Free Radicals; Glomerular Filtration Rate; Glutathione; In Vitro Techniques; Kidney; Kidney Transplantation; Organ Preservation; Oxygen; Perfusion; Proteinuria; Sodium; Superoxide Dismutase; Time Factors; Urine; Verapamil

Topics: Aminopeptidases; Animals; CD13 Antigens; gamma-Glutamyltransferase; Gentamicins; In Vitro Techniques; Kidney; Male; Mercuric Chloride; Nephrons; Ochratoxins; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Inbred F344; Rats, Inbred Strains; Xanthine Oxidase

The cellular processes responsible for the proteinuria induced by the aminonucleoside of puromycin (PA) remain inadequately defined. Hypoxanthine is both a metabolic breakdown product of PA as well as a substrate for xanthine oxidase, which catalyzes its enzymatic conversion to xanthine and uric acid, yielding the superoxide anion in the process. We examined whether oxygen free radical production contributes to the development of proteinuria in this model. Seven groups of male Sprague-Dawley rats were studied. Proteinuria was quantitated and histology examined 7 days after rats were treated with PA intravenously over 5 min. PA-treated animals received either saline, dimethyl sulfoxide, superoxide dismutase, or catalase over 30 min prior to and 30 min following PA administration. Another group received allopurinol over 4 hr prior to PA. The superoxide dismutase and allopurinol treatment groups had a significant suppression of urinary protein excretion compared to the PA control group. There were also less severe glomerular morphologic changes in the superoxide dismutase group vs. the PA controls, which demonstrated a pathologic pattern that included epithelial cell blebbing, segmental mesangial cell proliferation and matrix expansion, loss of glomerular capillary lumina, and occasional adhesions between the glomerular tuft and Bowman's capsule. The allopurinol group exhibited normal glomerular morphology on light microscopy, with the exception of occasional epithelial cell blebs. All groups showed spreading of the epithelial cell cytoplasm along the glomerular basement membrane with loss of foot processes, focal areas of lifting of the epithelial cell from the glomerular basement membrane, cytoplasmic vacuolization, and protein reabsorption droplets; however, allopurinol-treated animals demonstrated these changes to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Allopurinol; Animals; Catalase; Depression, Chemical; Dimethyl Sulfoxide; Disease Models, Animal; Free Radicals; Male; Nephrosis; Oxygen; Proteinuria; Puromycin; Puromycin Aminonucleoside; Rats; Rats, Inbred Strains; Superoxide Dismutase

Topics: Allopurinol; Colchicine; Diabetes Complications; Gout; Humans; Hypertension; Indomethacin; Kidney Diseases; Obesity; Proteinuria; Socioeconomic Factors; Synovial Fluid; Uric Acid; Urinary Calculi

A 33-year-old man with overall renal function in the lower normal range had daily excretion in the urine of between 31 and 70 gm of protein composed entirely of free monoclonal K light chains. K light chains were also present in the serum. Serum protein electrophoresis and findings on bone marrow and lymph node biopsy were diagnostic of light chain disease. Amyloid was absent from renal tissue. General clinical improvement and almost total disappearance of protein from the urine followed treatment with phenylalanine mustard.

Topics: Adult; Allopurinol; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Male; Melphalan; Paraproteinemias; Proteinuria

Topics: Allopurinol; Bence Jones Protein; Drug Therapy, Combination; Female; Humans; Kidney Diseases; Male; Melphalan; Multiple Myeloma; Myeloma Proteins; Prednisone; Proteinuria

Topics: Allopurinol; Athetosis; Benzofurans; Brain; Child; Child, Preschool; Chorea; Compulsive Behavior; Erythrocytes; Female; Guanine; Humans; Hypoxanthines; Infant; Intellectual Disability; Japan; Kidney; Lesch-Nyhan Syndrome; Liver; Male; Proteinuria; Purine-Pyrimidine Metabolism, Inborn Errors; Self Mutilation; Transferases; Uric Acid

Topics: Adolescent; Adult; Allopurinol; Diet Therapy; Diet, Sodium-Restricted; Diuretics; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Tubules; Male; Piperazines; Proteinuria; Purine-Pyrimidine Metabolism, Inborn Errors; Uric Acid

Topics: Allopurinol; Colchicine; Crystallization; Diagnosis, Differential; Diet Therapy; Gout; Humans; Indomethacin; Joint Diseases; Kidney Diseases; Kidneys, Artificial; Phenylbutazone; Probenecid; Proteinuria; Purines; Radiography; Salicylates; Steroids; Sulfinpyrazone; Uric Acid