BUN Values Research Articles

PP-363 Comparision of Tolvaptan Treatment with Ultrafiltration Theraphy in Cardiac Edema

In a group of patients, accepted our hospital with diagnosis of cardiac edema and treated inefficaciously with other known therapeutics such as furosemid, thiazid etc., tovaptan was used. Only 13 patients could be added to this study among the 25 patients treated with tovaptan. 13 patients having no exclusion criteria and treated with ultrafiltration thearapy were also accepted to the study. Tolvaptan was initiated 15 mg orally and weight, BUN, AST, ALT, Na and glucose values were documented. Values obtained after 24 hours were evaluated. Two or three liter of liquid was withdrawn from the patients for two or three hours after application of femoral or juguler catheterization for ultrafiltration therapy. Patients in need of dialysis and Na profile were not accepted to the study. In both of the study groups dermographic features, weight, Na and BUN values were compared. Because of expected metabolic effects, in tolvaptan group patients, blood glucose, AST and ALT values were compared before and after the therapy. In the tolvaptan group patients treatment of hiponatremia was more efficious than ultrafiltration patients and weight loss was more in ultrafiltration group significantly. No change was seen in blood glucose value in tolvaptan group patients and decrease seen in AST and ALT values for this group has no significance statistically. No complication has been seen in both of the groups in 24 hours. Tolvaptan therapy in cardiac edema has rapid and effective therapeutic value.Tabled 1

Abstract 163: Carotid Stenosis and Stroke Recurrence in Minor Stroke Patients With Atrial Fibrillation

Background & Purpose: Both atrial fibrillation (AF) and carotid stenosis (CS) can be associated with acute stroke recurrence and consequent bad outcome even in minor stroke. We investigated stroke recurrence and outcome in Japanese minor stroke patients with AF and/or CS. Subjects & Methods: Among the consecutive 6246 stroke patients who were admitted to the 7 stroke centers within 7 days after the onset, 634 patients with acute ischemic stroke with AF, the initial NIH stroke scale score of 7 or less, and prior modified Rankin scale (mRS) of 0 or 1 were included in the present study. We observed an acute stroke recurrence during 3 weeks. Results: Acute stroke recurrence was observed in 27 (4.3%) patients. Major cerebral artery stenosis of 50% or more in diameter was observed in 159 (25.1%) patients, and among them 43 (6.8%) had carotid stenosis. Any major artery stenosis was more frequent in patients with than without stroke recurrence (55.6% vs 23.7%, p=0.0002). Carotid stenosis was more frequent in patients with than without stroke recurrence (25.9% vs 5.9%, p<0.0001). The initial NIHSS score was not different between patients with and without an acute stroke recurrence. Dyslipidemia, diabetes mellitus, and history of brain hemorrhage were more frequent, and HDL cholesterol and estimated GFR values were lower, and HbA1c, fasting glucose, BUN, and D-dimer values were higher, intima-media thickness 0f the common carotid artery was thicker in patients with than without an acute stroke recurrence. On the multivariate analysis, carotid stenosis (OR 4.93, 95%CI 1.60~15.2) and D-dimer value (OR 1.13, 95%CI 1.00~1.28) had a positive association with an acute stroke recurrence. Among 43 patients with both AF and CS, 7 had an acute stroke recurrence. With regard to the acute antithrombotic treatment, 5 patients were treated with only anticoagulant agents and other 2 patients were treated with both anticoagulant and antiplatelet agents. Conclusions: Carotid stenosis was a significant predictor for an acute stroke recurrence in patients with atrial fibrillation. Optimal antithrombotic treatment in the acute phase in stroke patients with both AF and CS should be investigated.

Combined Extracts of Bryophyllum pinnatum and Aloe Barbadensis Induce Hepato-renal Dysfunctions and Elevated Hematological Indices in Wister Rats

The study was conducted to investigate the safety of combined extracts of Bryophyllum pinnatum (family: Crassulaceae) and Aloe barbadensis (family: Xanthorrhoeaceae) in rats. Forty rats were randomly selected and divided into four groups. Rats in groups I were administered with placebo as the control animals, while rats in groups II, III and IV were administered with aqueous extracts at 25mg/ml, 50mg/ml and 100mg/ml respectively for 28 days. Five milliliter (5ml) of blood was collected from either the ocular vein or aorta of each animal for evaluation of baseline and post – treatment values of AST, ALP, ALT, BUN, Total protein, and Creatinine, WBC, RBC, Platelet, MCV, MCH and MCHC. Data were expressed as Mean±Standard Error of Mean and analyzed using oneway ANOVA. Difference of means was considered statistically significant at P 0.05). Rats in groups II, III and IV exhibited significant increase in values of WBC, RBC, Platelet, MCV and MCH (P 0.05). Administration of the combined extracts may be tolerated at ≤25mg/kg bodyweight, if prolonged administration is avoided.

Subacute toxicopathological studies of tamoxifen in Wistar rats

The present research work was conducted in 24 male and 24 female Wistar rats to study the toxicoathological effects of repeated dose (28 days) of tamoxifen. Wistar rats were randomly divided into four different groups with six males and six females in each group. Animals of group II to IV were given 1, 10 and 20 mg/kg b.wt tamoxifen respectively by oral gavage for 28 days where as group I was administrated only 0.5% carboxymethylcellulose (vehicle) as control. After completion of 28 days treatment, blood samples were collected for hematology and serum biochemical analysis from retro-orbital plexus with the help of capillary tube. The animals were sacrificed on 29th day and necropsy examination was performed. Symptoms like weakness, loss of appetite, aggressiveness and mild alopecia were noticed in rats of high dose group. A dose dependant significant rise in mean values of AST and ALT were observed in group III and group IV whereas the mean values of AKP, creatinine and BUN were increased significantly in the group IV. All the rats exposed to tamoxifen at three different dose levels revealed dose dependant pathological changes in group III and IV in different organs. The lesions were characterized by degeneration, necrosis, inflammatory and vascular changes in liver, testes and uterus, which suggested that tamoxifen was hepatotoxic as well as toxic to reproductive system.

Toxicopathological studies of meloxicam, ibuprofen and diclofenac sodium in broiler chicks

The present research work was conducted on eight groups of day old Cobb-400 broiler chicks to study the toxicopathological effects of meloxicam, ibuprofen and diclofenac sodium. Clinical signs viz. dullness, depression, anorexia, lameness, unthriftiness with ruffled feather, drooping of the wings and lethargy with shrunken eyes were noticed in birds of diclofenac treated group II. During the study, 25% mortality was observed in diclofenac treated group. Meloxicam and ibuprofen treated birds did not have any mortality. Reduction in body weight gain and feed intake and increase in Kidney:Bodyweight ratio were observed in diclofenac treated group II as compared to control group. The average FCR was higher in diclofenac treated group (3.82) as compared to control group (2.19). There was significant rise (p<0.01) in mean values of serum uric acid, BUN, creatinine, AST and ALT in diclofenac treated group. Ibuprofen treated group with high dose revealed significant increase in AST and ALT. Gross and microscopic lesions of visceral gout were mainly observed in chicks that died during the experiment from diclofenac treated group. The overall lesions showed that diclofenac was nephrotoxic and hepatotoxic in nature. Ibuprofen treated group with high dose showed slightly enlarged and pale liver in few birds while meloxicam treated groups did not reveal any pathomorphological changes.

Detection and management of latent infection ofTrypanosoma evansiin a cattle herd

A study was conducted to evaluate the sensitivity of PCR based method for detection of T. evansi and to know its efficacy of corresponding trypanocidal treatment. A total of 101 random blood samples collected from the dairy farm were examined for the presence of Trypanosoma evansi infection. Polymerase Chain Reaction (PCR), using 21/22 mer primers, targeting repetitive sequence probe pMuTec 6.248 to yield 227 bp products was employed. The PCR detected 46.5% animals positive for T. evansi infection in comparison to only 6.9% detected by microscopy using Giemsa stained blood smears. Treatment of infected animals with Triquin (quinapyramine sulphate and chloride) showed improvement in general body condition within a period of two weeks. Results of PCR were also negative for T. evansi in all the post treatment blood samples. Subsequently all the 1400 animals at farm were treated with Triquin. After a period of one month, significant increase in levels of RBC, Hb and HCT and return of the values of BUN and TBIL of treated animals towards normal endorsed the effectiveness of the treatment.

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Introduction: We designed a Quality Improvement pilot initiative to improve response time and standardize early goal directed therapy (EGDT) for Emergency Department (ED) patients with severe sepsis needing immediate surgery ('surgical sepsis'). Our aim was to reduce mortality for surgical sepsis patients, similar to the reductions seen after initiating our EGDT program for medical sepsis patients Methods: In May 2011, we initiated the 'Surgical Sepsis' pilot initiative at the Kaiser Permanente Northern California Santa Clara Medical Center-one of our tertiary medical centers. This pilot included a 6 month period in which we used standard performance improvement methodology (e.g., small tests of change) to accelerate quality improvement. We screened ED patients to identify those who: (1) were jointly evaluated by the ED physician and the Surgical consultant; (2) were thought to require a direct transfer from the ED to the operating room (OR) because of a surgical source of infection; and (3) met criteria for high-risk severe sepsis or shock. These criteria included a serum lactate equal to or greater than 4 mmol/L, persistent hypotension after 2 liters of intravenous (IV) crystalloid infusion, or a predicted mortality >14% based on our BUN/Lactate grid stratifying risk of mortality based on BUN and Lactate values. Among these 'Surgical Sepsis' patients, we administered a bundle comprised of at least 40 mL/kg of IV fluids, appropriate antibiotics within one hour of surgical consult, insertion of a central venous catheter within 2 hours of surgical consult, and subsequent EGDT-based quantitative resuscitation. Results: We screened a total of 759 patients seen by the Surgical consultation service with 358 deemed appropriate for admission by the surgical service. The most frequent surgical services were general surgery (abdominal surgeries). Of these patients, 273 (76.3%) received antibiotics in the ED and 198 (55.3%) met SIRS criteria. Most SIRS patients had a lactate level checked (178, 89.9%). From this sample, seven patients received our Surgical Sepsis bundle including three who met traditional severe sepsis/shock criteria and four who met BUN/Lactate criteria. Their mean age was 52 (34-85) and their mean lactate level was 3.82 mmol/L (0.94-6.2). All patients underwent emergency surgery with general anesthesia. Thirty-day survival was 100%. Conclusions: A surgical sepsis pathway can effectively enhance patient identification and treatment through a quality improvement process in a nonacademic tertiary care medical center.

Anti-CD38 Pretargeted Radioimmunotherapy Eradicates Multiple Myeloma Xenografts In a Murine Model

Novel therapies, including immunomodulatory agents (thalidomide, lenalidomide and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib) have improved response rates and prolonged progression free survival for patients with multiple myeloma (MM). Despite these advances the disease remains incurable. MM persistence is presumably due to residual malignant plasma cell clones that evade or develop resistance to available therapies. The efficacy of radioimmunotherapy (RIT) in the treatment of hematologic malignancies is well established and the radiosensitivity of malignant plasma cells has been demonstrated in both preclinical and clinical settings. CD38 is a plasma cell antigen that exhibits relatively specific, stable and uniform expression (95-100%) at a high epitope density on myeloma cells, making it an attractive target for antibody based therapies, including RIT. Recently, the unmodified CD38 mAb daratumumab has demonstrated anti-MM tumor cell activity both in vitro and in mouse xenografts, validating the antigen as a desirable target. Pretargeted RIT (PRIT), using a multi-step streptavidin (SA)-biotin targeting system enhances the therapeutic index of delivered radiation. We have generated an anti-CD38 antibody (Ab)-SA chemical conjugate (OKT10-SA). The OKT10-SA construct binds with high avidity to myeloma cells while retaining full biotin-binding capability for radiolabeled DOTA-biotin.Blood, tumor and nonspecific organ uptakes of OKT10-SA directly measured in biodistribution experiments involving athymic nude mice bearing human MM xenograft tumors (Green, et al. ASH 2011) demonstrated tumor-to-normal organ ratios of absorbed radioactivity that were 8:1; 10:1; 8:1; and 6:1 respectively for blood, lung, liver and kidney in mice pretargeted with OKT10-SA; compared to 0.6:1; 0.9:1; 0.8:1 and 0.4:1 respectively, in control mice pretargeted with the IgG1 isotype matched control Ab BHV1-SA (bovine herpes virus-1).In therapy studies athymic nude mice (n=9-10/group) bearing s.c. NCI-H929 human MM xenograft tumors received 1.4 nmol (300 µg) of either OKT10-SA (anti-CD38 SA) or BHV1-SA 22 hrs prior to synthetic biotin-acetyl-galactosamine clearing agent (CA; 5.8 nmol [50 µg]) and 24 hrs prior to 90Y-DOTA-biotin (2 µg) labeled with 800 µCi per mouse. Previously, a dose range of 800 µCi to 1200 µCi was identified as optimal when the high energy beta particle emitter 90Yttrium (t1/2 = 64 hrs) was used as the therapeutic radionuclide in a MM xenograft model (Green, et al. ASH 2011). All mice in the BHV1-SA control group experienced exponential MM tumor growth and 100% of these control animals required euthanasia within 37 days. All mice pretargeted with OKT10-SA demonstrated tumor shrinkage by day 6. After 70 days, 100% of the OKT10-SA treated animals remained alive and objective remissions were observed within 6 days in 100% of the mice treated with OKT10-SA followed by 800 µCi of 90Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in OKT10-SA treated mice) compared to tumors that were 2982 ± 2834% of initial tumor volume [p<0.0001, Student's t-test] in untreated control animals by day 23 [Figure]. Hepatic and renal function was assessed 160 days after mice received OKT10-SA followed by 90Y-DOTA-biotin (800 µCi, n=5) and no significant toxicity was observed. The measured serum creatinine was <0.4 mg/dl in all animals, the average BUN, ALT and AST values were 48 + 33 mg/dl, 46.8 +40 and 120.4 + 116.7 U/L respectively. The observed anti-tumor activity in this model was not attributable to an effector response mediated by the CD38 mAb in the absence of radiolabeled DOTA-biotin. Mice bearing MM xenografts (n=10) treated with OKT10-SA administered alone (without subsequent 90Y-DOTA-biotin infusion) demonstrated no objective tumor responses and 100% required euthanasia by day 17 for tumors that were 7837 ± 3492% of their initial volume. In a matched cohort of mice (n=10) treated concurrently with identical doses of OKT10-SA followed by CA and 90Y-DOTA-biotin (800µCi), 100% of the treated animals achieved a complete remission by day 17 and 70% of these animals were alive and tumor free at day 80.Tumor responses in this MM xenograft tumor model are encouraging and results support further evaluation of both PRIT and CD38 targeted RIT in MM. Studies combining PRIT and novel agents are ongoing in both xenograft and SCID-hu MM models. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Osseous and Nonosseous Bone Scan Findings in Liver Transplant Candidates with end-stage Chronic Liver Disease

Objective: End-stage chronic liver disease (CLD) adversely affects the function of multiple organ systems including the skeletal system. The aim of this study was to assess osseous and nonosseous bone scintigraphy (BS) findings in liver transplant (LT) candidates with end-stage CLD.Methods: We retrospectively evaluated BS findings in 50 consecutive patients with end-stage CLD who were undergoing preoperative assessment for LT from January 2006 to December 2011. All the patients were analyzed with respect to clinical and laboratory parameters, and BS findings. Scintigrams were visually assessed for the presence of osseous and nonosseous abnormalities. Osseous abnormalities were classified as those indicating bone metabolism changes or metastatic bone disease. Typical scintigraphic findings denoting to changes in bone metabolism were the presence of decreased osseous uptake, increased periarticular uptake, asymmetrical or unusual uptake patterns. Nonosseous findings were classified according to the degree of soft-tissue uptake as mild and severe.Results: The group consisted of 46 adult and 4 adolescent patients. All adolescent patients had normal skeletal accumulation with growth plate uptake and one had mildly increased renal cortical activity. A total of 46 adult patients had one or more of the following osseous findings: generalized decrease in osseous uptake (n=4, 8.7%); bilateral decrease in lower extremity uptake (n=26, 56.5%); symmetrically increased periarticular uptake (n=26, 56.5%); bilateral cortical/periosteal increased uptake in the lower extremity indicating hepatic hypertrophic osteoarthropathy (HOA) (n=8, 17.4%); bilateral increased sacroiliac activity (n=16, 34.8%); sacral activity (n=10, 21.7%), coccygeal activity (n=2, 4.3%), focally increased uptake suggestive of metastases (n=5, 10.9%). Three rib metastases appeared to be linear. Nonosseous findings observed in adult patients were mild diffuse liver uptake (n=4, 8.7%) and bilateral diffuse mild or severe degree of renal cortical uptake (n=20, 43.5%). There was a statistically significant difference in serum creatinine values between mild and severe renal uptake groups (p<0.05). There was also statistically significant difference in serum BUN and creatinine values between patients with severe degree of renal uptake and without renal uptake (p<0.05).Conclusion: The results of the current study has shown that adolescent LT candidates with end-stage CLD had no osseous abnormality on BS. However, all of adult patients exhibited one or one more osseous abnormalities. Typical scintigraphic findings denoting to abnormalities in bone metabolism were generalized decreased osseous uptake, decreased lower extremity osseous uptake, increased periarticular uptake, increased cortical/periosteal uptake indicating hepatic HOA, and other unusual uptake patterns. Hepatocellular carcinoma metastases may present itself as rib metastases linear in pattern. Soft-tissue uptake in the form of diffuse bilateral mild or severe degree of renal uptake and less commonly mild diffuse liver uptake can be observed. Increased renal uptake may be an early marker of renal dysfuntion or a predictor of hepatorenal syndrome. Conflict of interest:None declared.

Effects of Dietary Arginine and Glutamine on Alleviating the Impairment Induced by Deoxynivalenol Stress and Immune Relevant Cytokines in Growing Pigs

Deoxynivalenol (DON) is a mycotoxin that reduces feed intake and animal performance, especially in swine. Arginine and glutamine play important roles in swine nutrition. The objective of this study was to determine the effects of dietary supplementation with arginine and glutamine on both the impairment induced by DON stress and immune relevant cytokines in growing pigs. A total of forty 60-d-old healthy growing pigs with a mean body weight of 16.28±1.54 kg were randomly divided into 5 groups, and assigned to 3 amino acid treatments fed 1.0% arginine (Arg), 1.0% glutamine (Gln) and 0.5% Arg+0.5% Gln, respectively, plus a toxin control and a non-toxin control. Pigs in the 3 amino acid treatments were fed the corresponding amino acids, and those in non-toxin control and toxin control were fed commercial diet with 1.64% Alanine as isonitrogenous control for 7 days. The toxin control and amino acid treatments were then challenged by feeding DON-contaminated diet with a final DON concentration of 6 mg/kg of diet for 21 days. No significant differences were observed between toxin control and the amino acid groups with regard to the average daily gain (ADG), although the values for average daily feed intake (ADFI) in the amino acid groups were significantly higher than that in toxin control (P<0.01). The relative liver weight in toxin control was significantly greater than those in non-toxin control, arginine and Arg+Glu groups (P<0.01), but there were no significant differences in other organs. With regard to serum biochemistry, the values of BUN, ALP, ALT and AST in the amino acid groups were lower than those in toxin control. IGF1, GH and SOD in the amino acid groups were significantly higher than those in toxin control (P<0.01). The IL-2 and TNFα values in the amino acid groups were similar to those in non-toxin control, and significantly lower than those in toxin control (P<0.01). These results showed the effects of dietary supplementation with arginine and glutamine on alleviating the impairment induced by DON stress and immune relevant cytokines in growing pigs.

Renal cell cancer (RCC): Use of metformin in the setting of renal impairment.

e15551 Background: Metformin is a biguanide that is widely used to treat type-2 diabetes and prediabetic syndromes. It has been found to inhibit RCC cell proliferation through activation of AMP-activated protein kinase (AMPK) and downstream inhibition of mammalian target of rapamycin (mTOR). Metformin is associated with potentially life threatening lactic acidosis (LA), but a clear link has not been established. We evaluated the occurrence of lactic acidosis in metformin-treated RCC patients with renal impairment. Methods: A retrospective study of 65 RCC patients treated with 250 to 2000 mg of metformin daily was conducted. Demographic data including age, gender, and ethnic background were collected. Data were collected on median metformin dose, eGFR, dialysis status, lactic acid, BUN, Na, K, Cl, and CO2 values. Results: Median metformin dose was 1000 mg daily in each group. Fifteen patients (23%) had elevated lactic acid &gt;4. The mean eGFR for patients with elevated lactic acid of &gt;4 vs. &lt;4is comparable (p=0.98). The two populations were significantly different at the BUN baseline level: patients with lactic acids &gt;4 have statistically significant smaller median baseline BUN level (median of 19.0 vs. 19.5; Wilcoxon two-sample p=0.03). Moreover, there is a marginally significant difference in age between these 2 groups (Mean of 58 vs. 62.8, Student's t-test p=0.07). Conclusions: Regardlessof lactic acid elevation, patients did not experience lactic acidosis. Complete data will be presented. [Table: see text]

TOXICOLOGICAL STUDIES ON ISEPAMICIN (HAPA-B)

Acute toxicity of isepamicin (HAPA-B), a new aminoglycoside antibiotic, in mice, rats and dogs was examined in comparison with amikacin (AMK) and gentamicin (GM). Intravenous LD50 values of HAPA-B were 234 mg/kg in male and 236 mg/kg in female for mice, 489 mg/kg in male and 476 mg/kg in female for rats and 720-864 mg/kg for dogs. Those of AMK were 183 mg/kg in male and 181 mg/kg in female for mice, 420 mg/kg in male and 417 mg/kg in female for rats. Those of GM were 50 mg/kg in male and 47 mg/kg in female for mice, 119 mg/kg in male and 124 mg/kg in female for rats. Intraperitoneal LD50 values of HAPA-B were 2,244 mg/kg in male and 2,272 mg/kg in female for mice, 1,664 mg/kg in male and 1,591 mg/kg in female for rats. Intramuscular LD50 values of HAPA-B were 2,508 mg/kg in male and 2,632 mg/kg in female for mice, 2,088 mg/kg in male and 2,111 mg/kg in female for rats and greater than 1,800 mg/kg for dogs. Those of AMK were 1,247 mg/kg in male and 1,334 mg/kg in female for mice, 2,324 mg/kg in male and 2,244 mg/kg in female for rats. Those of GM were 359 mg/kg in male and 360 mg/kg in female for mice, 559 mg/kg in male and 557 mg/kg in female for rats. Subcutaneous LD50 values of HAPA-B were 3,321 mg/kg in male and 3,320 mg/kg in female for mice, 3,451 mg/kg in male and 3,392 mg/kg in female for rats. Oral LD50 values of HAPA-B were more than 5,000 mg/kg in mice and rats. Ataxia, acratia, dyspnea and convulsions were observed following administration by all routes, except for oral route, of all drugs in mice, rats and dogs. The cause of early death was due to respiratory paralysis which is the typical acute toxic sign of aminoglycoside antibiotics, and that of late death was due to renal injuries. BUN and creatinine values of surviving dogs after day 14 increased after administration by either intravenous or intramuscular routes. Disintegration, necrosis and calcification of epithelial cells of the proximal convoluted tubuli were observed in rats which died during the course of the study, and atrophy, dilatation and eosinophilic degeneration in epithelial cells of the proximal convoluted tubuli and thickening of Bowman's capsule were observed in surviving dogs.

Prevalence of chronic renal failure in COPD patients

BackgroundCOPD is a leading cause of death worldwide. It is associated with a large number of comorbidities. MethodsThe current study included 300 COPD patients aged 65.28±6.32years, 148 of them (49.3%) were females and the rest were males and 300 control age and gender matched patients with diseases other than COPD; aged 64.70±7.12years, 138 of them (46%) were males and the rest were females. They were enrolled in the study during their follow up visits to the outpatient clinic of the Chest Department, Menoufiya University Hospitals from August 2009 to August 2012. The GFR was estimated and patients were categorized according to their renal function as having normal renal function (GFR⩾60mL/min/1.73m2), concealed CRF (normal serum creatinine and GFR<60mL/min/1.73m2), or overt CRF (increased serum creatinine and GFR<60mL/min/1.73m2). ResultsIn the COPD group; the mean BUN value was 22.86±13.63, the mean serum creatinine concentration was 1.29±0.67mg/dL and the mean estimated GFR was 75.20±35.78mL/min/1.73m2. In the control group; the mean BUN value was 14.04±9.61, the mean serum creatinine concentration was 0.85±0.34mg/dL and the mean estimated GFR was 92.04±25.54mL/min/1.73m2 (P<0.01 for all in comparison with the COPD group). The prevalence of normal renal function, concealed CRF, and overt CRF in COPD group of patients was 54%, 26% and 20%, respectively. The corresponding figures in the control group were 78%, 10%, and 12%, respectively (COPD vs control group: P<0.001). The overall prevalence of CRF (GFR<60mL/min/1.73m2) was 46% in the study group and 22% in the control group (P<0.001). COPD was significantly associated with both concealed and overt CRF. Age and hypoalbuminemia were significantly associated with overt CRF while the number of comorbidities was significantly associated with concealed CRF. ConclusionsCRF may be an important COPD comorbidity and should be screened for not only by serum creatinine level but also by the estimated GFR.

Contrasting Effects of Systemic Monocyte/Macrophage and CD4+T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease

Using a reversible UUO model (rUUO), we have demonstrated that C57BL/6 mice are susceptible to development of CKD after obstruction-mediated kidney injury while BALB/c mice are resistant. We hypothesized that selective systemic depletion of subpopulations of inflammatory cells during injury or repair might alter the development of CKD. To investigate the impact of modification of Th-lymphocytes or macrophage responses on development of CKD after rUUO, we used an anti-CD4 antibody (GK1.5) or liposomal clodronate to systemically deplete CD4+ T cells or monocyte/macrophages, respectively, prior to and throughout the rUUO protocol. Flow cytometry and immunohistochemistry confirmed depletion of target cell populations. C57BL/6 mice treated with the GK1.5 antibody to deplete CD4+ T cells had higher BUN levels and delayed recovery from rUUO. Treatment of C57BL/6 mice with liposomal clodronate to deplete monocyte/macrophages led to a relative protection from CKD as assessed by BUN values. Our results demonstrate that modulation of the inflammatory response during injury and repair altered the susceptibility of C57BL/6 mice to development of CKD in our rUUO model.

Sulforaphane decreases kidney injury after transplantation in rats: role of mitochondrial damage

Sulforaphane is a naturally occuring antioxidative and anti-inflammatory isothiocyanat. In this study, its impact on experimental kidney transplantation was evaluated. Male Brown Norway rats (n=112) were used as experimental animals. Donor kidneys were harvested and stored for 12 hours in HTK-solution at 4°C. D,L-Sulforaphane (4.4 mg/kg BW; 0.2ml) or normal saline (0.2 ml) was given i.v. to the recipients 24 and 1 hour before, and 6 hours after transplantation. Recipients were nephrectomized bilaterally and subsequently transplantation was performed. After 6 and 48 hours, biopsies were taken and processed for light and electron microscopy. Graft function was monitored using serum values of creatinine and BUN after 6 and 24 hours. Quantitative real-time PCR was used to detect differences in SOD2-gene expression after 6 hours and apoptotic activity was detected after 6 hours using propidium iodide flow cytometry. Recipient preconditioning improved reperfusion damage index from 12.8±1.6 in controls to 8.8±1.8 (p<0.001). Serum levels of creatinine and BUN decreased from 4.29±0.25 mg/dl and 119±23 mg/dl in controls to 3.65±0.7 mg/dl and 81±19 mg/dl (p<0.05). The number of severely injured tubules decreased (p<0.05). Apoptotic activity was increased in SFN-treated rats. Mitochondrial microstructure was better preserved after SFN, while SOD 2 gene expression increased (p<0.05). SFN ameliorates ischemia/reperfusion injury after KTx, most likely through anti-oxidative effects.

Potentials of Cystatin C and Uric Acid for Predicting Prognosis of Heart Failure

Few studies have explored the clinical potentials of combined Cystatin C (Cys) and uric acid (UA) in heart failure (HF). The authors evaluated Cys and UA as predictors of clinical outcomes compared with conventional renal biomarkers. This prospective cohort study included 587 HF patients presenting with dyspnea. At admission, Cys, UA, and other renal measures including serum urea nitrogen (BUN), creatinine (Cr), and glomerular filtration rate (GFR) were obtained. The primary endpoint was the composite of cardiac death and rehospitalization for worsening HF. During a 25-month median follow-up period, 68 patients experienced clinical outcomes: 9 cardiac deaths and 59 HFs. They showed higher BUN and Cr values and lower GFR. Within these parameters, Cys and UA had the most favorable area under the curves, and patients with Cys ≥0.8 mg/L and UA ≥6.6 mg/dL showed more frequent events. The net reclassification improvement analysis showed the combination of Cys and UA had a greater incremental effect for cardiac prognosis. On multivariate Cox hazard analysis, Cys and UA were independent predictive markers for clinical outcomes. In HF patients presenting with dyspnea, Cys and UA appear to be more useful predictors of clinical events than other renal measures.

Contractile responses of urinary bladder in an experimental model of chronic renal failure

Chronic kidney disease is a public health problem with increasing prevalence caused by diabetes, hypertension and glomerulonephritis. Number of publications investigate the lower urinary tract dysfunction due to CKD is limited. There is a high incidence of bladder dysfunction of different degrees in patients with renal failure. Mechanism of the lower urinary tract dysfunction in these patients is not well known. In this study, we aimed to investigate the effects of CKD on detrusor function in a rat model of CKD. In our study, 20 Wistar Albino rats have been divided into two groups as CKD and control groups. To the experiment group, left partial nephrectomy and right nephrectomy have been applied. CKD confirmation has done with the BUN and creatinin values from the blood of the rats. The bladder strips were prepared from the CKD and control groups and its contractile responses were evaluated in-vitro. There wasn't a considerable difference with the contractile responses caused by carbachol, KCL. There was a considerable increase in the contractile responses caused by ATP, ADP and electrical field stimulation on the behalf of the CKD group. The present study demonstrated that isolated DSM of CKD group showed significantly increased contraction responses to purinergic agonists ADP, ATP and atropine resistant component in electrical field stimulation-induced contractions as compared to those of the control group. Bladder overactivity and reduced bladder volume in CKD patients might be due to the change in purinergic system.

Treatment of patent ductus arteriosus (PDA) using ibuprofen: renal side-effects in VLBW and ELBW newborns

Objectives: This study aims to determine whether or not treatment of preterm neonates with PDA using IV ibuprofen can impair renal function and in what range of birth weights and gestational ages the risk of major renal side-effects due to ibuprofen is highest. Methods: 134 preterm newborns with PDA were enrolled and randomized to receive either placebo or a 3-day-course (10, 5 and 5 mg/kg) of IV ibuprofen. 67 newborns (mGA: 27+3 w and mBW: 989 g) with PDA received ibuprofen. Results: Subdividing the infants according to BW and to GA, the values of creatinine and BUN were only significantly higher than initial values at the end of the therapy in newborns with a BW ≤1000 g and/or GA ≤26 weeks. Renal impairment is greater the lower the weight and gestational age of the infant at birth. Conclusions: Ibuprofen significantly impairs renal function in preterm infants with a GA ≤26 weeks and/or in ELBW neonates, while it may be considered safe for infants with a BW >1000 g and/or GA >26 weeks. Thus, before starting therapy with IV ibuprofen, it is essential to take into account the BW and GA of newborns and the effective need for treatment from the point of view of the ratio of risks to benefits, due to its substantial renal side-effects.

Contrast-induced nephropathy: controlled study by differential GFR measurement in hospitalized patients

Without appropriate control measures, contrast-induced nephropathy (CIN) incidence has been claimed to be overestimated. To evaluate the relationship and the difference between differential serum creatinine (DsCr), which is currently surrogating as a marker of CIN, and measured differential GFR values as a control measure (DGFR) in hospitalized patients. GFR was measured two times by Tc-99m DTPA, before and 48 h after contrast media (CM), along with sCr and BUN in 35 inpatients (22 men, 13 women, mean age ± SD = 61 ± 14) with no known chronic kidney disease. Relationship was moderate between GFR and sCr (R = 0.50, P < 0.01) in the study population. Pre-CM vs. post-CM values of GFR, sCr and BUN were not statistically different as (mean ± SD); 78 ± 36 vs. 73 ± 35 mL/min/1.73m(2), 0.95 ± 0.26 vs. 0.94 ± 0.26 mg/dl and 21 ± 16 vs. 19 ± 13 mg/dl, respectively, in the study group. According to basal GFR values, 14 patients (40%) seemed carrying risk of CIN (GFR < 60 mL/min/1.73m(2)) in whom only two had sCr >1.5 mg/dl. Twenty-five patients (71%) had discordant results in relation to DsCr and DGFR and two of them had CIN according to classical definition of DsCr, although having basal sCr <1.1 mg/dl. Yet, both had low, but stable GFR values. None of patient from the study group underwent hemodialysis. Significant discordance was observed between differential serum creatinine and measured differential GFR in hospitalized patients, suggesting that CIN incidence calculations only based on hospital registry may carry risk of error.

Efficacy and Safety of Changing From Cyclosporine C 0 to C 2 Monitoring in Stable Recipients Following Renal Transplantation: A Prospective Cohort Study

Cyclosporine doses can be adjusted individually to decrease the occurrence of rejection and nephrotoxic episodes using concentrations at 2 hours postdosing (C 2). However, some transplantation centers still use tough concentrations (C 0) to adjust cyclosporine doses among stable renal transplant recipients. We analyzed the efficacy and safety of changing from monitoring C 0 to C 2 among stable recipients following living relative donor renal transplantation. We enrolled 65 stable renal transplant recipients whose cyclosporine (Neoral) dosages were adjusted by C 0, recording their cyclosporine C 2 values. They were divided into low (<500 ng/mL, n = 25), target (500–600 ng/mL, n = 23), or high (>600 ng/mL, n = 17) C 2 groups. The cyclosporine dose was prospectively modified in the low and high C 2 groups; all patients were followed for 12 months. We compared the incidences of complications among their transplanted kidneys and other organs. Among patients in the high C 2 group, the C 2 target value was achieved by reducing the cyclosporine dose by up to 575.0 mg (mean = 33.8 mg/patient); 88.2% of patients showed stable levels of creatinine (Cr) and urea nitrogen (BUN) during the follow-up with decreased blood cholesterol and uric acid levels in some patients, while two subjects suffered acute rejection episodes. Among the low C 2 group, the target value was achieved by increasing the cyclosporine dose by up to 755.0 mg (mean = 30.2 mg/patient); during the follow-up with 84.0% of subjects displaying stable levels of Cr and BUN, four suffered increasing Cr and BUN values. Although most of stable recipients in this study benefited from C 2 monitoring, some patients suffered rejection or nephrotoxicity episodes. One must be cautious to change from monitoring C 0 to C 2 in stable recipients following renal transplantation.