Moderate Renal Dysfunction Research Articles

Impact of Mild to Moderate Renal Dysfunction on Left Ventricular Relaxation Function and Prognosis in Ambulatory Patients With Nonischemic Dilated Cardiomyopathy

The relationship between mild-to-moderate renal dysfunction and cardiac diastolic dysfunction and cardiac events in patients with nonischemic dilated cardiomyopathy (NDCM) has not been fully elucidated. The aim of this study was to investigate the relationship between renal and cardiac function, as well as clinical outcome in patients with NDCM.We measured plasma BNP and eGFR, and performed cardiac catheterization in 135 patients with NDCM. LV dP/dt(max)and T(1/2) were determined as indexes of LV contractility and isovolumic relaxation, respectively. During a mean follow-up of 4.8 years, we monitored all patients for the occurrence of cardiac events, which were defined as cardiac death (from worsening HF or sudden death) and unscheduled admission for decompensated HF. Patients were classified into 3 groups on the basis of eGFR (mL min(-1) 1.73 m(-2)): eGFR ≥ 90 (n = 23, group A), 60 ≤ eGFR < 90 (n = 70, group B), and 30 ≤ eGFR < 60 (n = 42, group C). Whereas LV dP/dt(max) did not significantly differ among the 3 groups, T(1/2) was significantly longer in groups B and C than in group A (P < 0.01). Event-free survival in group C was significantly lower than that in groups A and B (P = 0.014, log-rank test). These results suggest that even mild renal dysfunction is associated with LV isovolumic relaxation impairment. In addition, moderate impairment of renal function is independently associated with cardiac events in patients with NDCM.

Risk of renal failure in cancer patients with bone metastasis treated with renally adjusted zoledronic acid

The purpose of this study was to evaluate the incidence of acute renal failure (ARF) in patients with mild to moderate renal dysfunction, receiving renally adjusted zoledronic acid (ZA) and compare it to patients with normal baseline renal function, receiving standard-dose ZA. This was a retrospective study of patients receiving ZA for the treatment of bone metastasis due to cancer. Patients were divided into two groups: (1) normal group with baseline creatinine clearance (CrCl) of greater than 60 mL/min and standard ZA dose; (2) impaired group with baseline CrCl of 30-60 mL/min and renally adjusted ZA dose. Primary endpoint of ARF was defined as an increase in serum creatinine (SCr) of 0.5 mg/dL or 1.0 mg/dL from a baseline SCr of <1.4 mg/dL or ≥ 1.4 mg/dL, respectively. In total, 1,472 evaluable doses of ZA were given to 220 patients. Of these, 184 patients were in the normal group and 36 patients in the impaired group. There were 38 patients (20.7%) who developed ARF in the normal group versus 7 patients (19.4%) in the impaired group. There was no difference in the mean time to the incidence of ARF at 6.1 months in both groups. Incidence of ARF based on CrCl (≥ 25% decline in CrCl) was similar between groups (39.1% vs. 41.7%; p = 0.78). The incidence of ARF is similar between patients in the normal group and impaired group when the ZA dose is renally adjusted.

Intravenous N-acetylcysteine plus high-dose hydration versus high-dose hydration and standard hydration for the prevention of contrast-induced nephropathy: CASIS—A multicenter prospective controlled trial

BackgroundContrast-induced nephropathy (CIN) is a leading cause of acute renal failure and affects mortality and morbidity. We investigated the efficacy of prophylactic intravenous (IV) N-acetylcysteine (NAC) and hydration for the prevention of CIN in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and/or percutaneous coronary intervention (PCI). MethodsA total of 220 patients who had mild to moderate renal dysfunction with serum creatinine (SCr)≥1.1mg/dL or creatinine clearance≤60mL/min were randomized in 3 groups: 80 patients were assigned to IV NAC plus high-dose hydration with normal saline, 80 patients to only high-dose hydration with normal saline and 60 patients to standard hydration with normal saline (control group). The primary end point was the alteration of SCr level. The secondary end point was the development of CIN after the procedure. ResultsSCr levels changed the least in the NAC plus high-hydration group (P=0.004). The rate of the CIN in the NAC plus high-dose hydration group was also lower than the high-dose hydration group (P=0.006). No significant differences in the primary and secondary end points were found between high-dose hydration and control group. ConclusionThe results of this study suggest that NAC plus high-dose hydration was superior to high-dose hydration alone as well as standard hydration for the protection of renal functions in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and/or PCI. High-dose hydration without NAC was not better than standard hydration alone.

Clinical Features and Neurologic Severity in Stroke Patients with Mild to Moderate Renal Dysfunction

To evaluate the independent effect of moderate renal dysfunction on stroke severity and to disclose the clinical features of stroke patients with moderate renal dysfunction. We studied consecutive stroke patients presenting within 48 hours of onset. The National Institutes of Health Stroke Scale (NIHSS) score at the time of presentation was used as an index of stroke severity. Patients were categorized into 2 groups based on their estimated glomerular filtration rates (eGFRs). Of the 475 patients with an eGFR >15 mL per minute per 1.73 m(2), 158 patients (33.3%) had an eGFR <60 mL per minute per 1.73 m(2). These patients were older and included significantly more cases with hypertension and atrial fibrillation. The NIHSS score at the time of admission was higher among the patients with renal dysfunction. In a multivariable model with adjustments for other clinical background factors, moderate renal dysfunction was an independent predictor of the neurologic severity of stroke at the time of admission (odds ratio, 1.261; 95% confidence interval, 1.032-1.545; P = .0244). Stroke patients with moderate renal dysfunction had a higher prevalence of hypertension and atrial fibrillation. Moderate renal dysfunction was associated with a higher severity of stroke on admission.

Coronary syndrome Y: Should we focus more on extra-cardiac conditions including renal disease and its management?

⁎ Corresponding author. E-mail address: kyalta@gmail.com (K. Yalta). In their recently published article, Muxel S et al. reported amalewith coronary slow flow (CSF) as measured with increased thrombolysis in myocardial infarction (TIMI) frame counts (TFC), and comment on the different clinical presentations and pathophysiological mechanisms of coronary syndromeXandY [1].We agreewith the authors that coronary syndrome X is generally characterized by impaired coronary vasodilation andcoronaryflow reservewhile coronary syndromeYoccurs due to enhanced coronary resistance leading to CSF [1]. Endothelial dysfunction plays the central role in the pathogenesis of coronary syndrome X and Y [1] indicating their potential co-existence in a portion of cases. However, compared to isolated coronary syndrome X, coronary syndrome Y is more likely to accompany and/or be associated with extra-cardiac pathologies potentially associated with endothelial dysfunction and subclinical myocardial fibrosis, etc. The association between renal disease and coronary syndrome Y, as described below, may potentially harbour some diagnostic, therapeutic and prognostic implications, and has recently drawn particular attention in the clinical setting. Chronic renal failure (CRF) is well known to induce endothelial dysfunction and consequent coronary atherosclerosis possibly due to a variety of CRF-induced pathologies including increased levels of asymmetric-dimethylarginine (ADMA) [2], inflammatory response and oxidative stress, accompanying hypertension, etc. Similarly, coronary syndrome Y (characterized by CSF) may be encountered in the setting of CRF, and may be regarded as a marker of coronary microvascular dysfunction that is largely attributable to increased microvascular resistance associated with endothelial dysfunction, subclinical myocardial fibrosis and hypertrophy [2,3], etc. Endothelial dysfunction is alsowell known to contribute to the pathogenesis of CRF. Therefore, coronary syndrome Y, coronary atherosclerosis and CRFmay share the same clinicopathological background, to some extent indicating the complex relationship among these entities. A recently published study demonstrated significant reductions in coronary blood flow in patients with end-stage renal disease (ESRD) regardless of the degree of epicardial coronary artery stenosis [3]. In another previous study by our group including patients with mild to moderate renal dysfunction and angiographically normal coronary arteries, we were able to demonstrate significant reductions in coronary blood flow as measured with increased TFC values compared to the control group with normal coronary arteries and renal functions [2]. It is also of note that in the patient group of our study, the values of TFC and calculated glomerular filtration rate (GFR) were also found to be independently correlated [2] indicating the close link between coronary syndrome Y and renal failure. Therefore, in the clinical setting, renal failure may accompany (as a result of generalized endothelial dysfunction) and/or beassociatedwith coronary syndromeY. Even though the renal statusof the case reported by Muxel S et al. [1] was not reported, the patient might have suffered some kind of subclinical or incipient renal failure (even with normal blood-urea-nitrogen (BUN) and creatinine levels), and hence may need to be thoroughly evaluated via other diagnostic modalities (GFR calculation, renal imaging, etc.) along with subsequent close follow-up for the possible emergence or progression of renal failure. Itmay be suggested that among coronarymicrovascular syndromes, coronary syndrome Y is more likely to accompany and/or be associated with extra-cardiac conditions (renal disease, etc. even in the subclinical stage) indicating the need for thorough evaluation of patients with this syndrome via various diagnostic modalities. In the setting of coronary syndrome Y (isolated or in combination with coronary syndrome X), besides targeting enhancement of coronary bloodflow, earlier diagnosis andmanagementof associated conditions including renal failuremaybe of utmost clinical value in the management of coronary microvascular dysfunction, and may possibly improve clinical outcomes including renal and cardiac adverse events. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [4].

Disfunção renal moderada não está associada a Troponina T elevada em síndromes coronarianas agudas

Interpretation of troponin results in patients with acute coronary syndromes (ACS) and renal disease is confused by the fact that renal dysfunction increases troponin levels, regardless of myocardial necrosis. Although it has been demonstrated that end-stage renal disease is associated with elevated cardiac troponin T (cTnT) levels, it is not known whether this biomarker is altered by less than severe degrees of renal impairment. To evaluate whether moderate renal dysfunction is associated with cTnT elevation in patients with ACS. One hundred, forty-five individuals with ACS and creatinine clearance > 30 ml/min were studied. Creatinine clearance was estimated by the Cockcroft-Gault formula and cTnT was measured at hospital admission. Moderate renal dysfunction was defined as a creatinine clearance of 30-59 ml/min and positive cTnT as levels > 0.01 ug/l. No correlation was observed between creatinine clearance and cTnT (r = - 0.06, P=0.45). The levels of cTnT were similar among individuals in the first (median=0.05 ug/l), second (median=0 ug/l), third (median=0.07 ug/l) and fourth quartiles (median=0 ug/l) of creatinine clearance - P=0.63. Similarly, there was no difference in troponin values between individuals with moderate renal dysfunction (median=0.02 ug/l) and individuals with normal/near normal function (median=0.03 ug/l) - P=0.63. The prevalence of positive cTnT was similar between individuals with moderate renal dysfunction and normal/near normal renal function (55% vs 52%, P=0.65). Moderate renal dysfunction is not associated with cTnT elevation in patients with ACS.

E0475 Impact of anaemia on development of contrastinduced acute kidney injury AKI after percutaneous coronary interventions

ObjectiveThe aim of the present study was to assess the influence of anaemia on development of contrast-induced acute kidney injury (AKI) after percutaneous coronary intervention.MethodsThe subject group consisted of 1026...

Vildagliptin and its role in the treatment of diabetes mellitus

Type 2 diabetes mellitus is a most serious medical problem throughout the world. Traditional hypoglycemic agents do not ensure long-term control ofglycemia and fail to affect the natural course of DM. An ideal hypoglycemic medicine must be efficacious, safe, and convenient to use for the preventionof progressive deterioration of beta-cell function during prolonged therapy; also, it should have positive effect on the outcome of DM. The use of incretinsin the recent decade is a new promising approach to the management of DM2. The group of incretins includes gastrointestinal hormones released inresponse to food intake to stimulate insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a new class of hypoglycemic agents, have been inuse in this country for over 3 years. Vildaglyptin (Galvus) is a representative of DPP-4 inhibitors and GalvusMet is the sole combination of DPP-4inhibitor with metformin registered in Russia. The advent of incretin mimetics necessiatate revision of national and international guidelines for DM2therapy. Results of international clinical studies show that Galvus and GalvusMet are efficacious and safe, they ensure adequate control of glycemiafree from complications and side effects. An important advantage of these preparations is the possibility of their use by elderly patients with arterialhypertension and moderate renal dysfunction and by those at risk of cardiovascular disorders. The evidence-based Galvus information is highly convincing.The advantages of Galvus over traditional agents give reason to recommend it as a medicine of choice for the initiation of DM2 therapy. Approvedcombinations of Galvus with other hypoglycemic agents may be used at all stages of intensive therapy of DM2.

Fracture risk in secondary osteoporosis

In this review, we focused on diabetes mellitus (DM) , chronic kidney disease (CKD) , and glucocorticoid-induced osteoporosis (GIO) , which frequently occurred in the clinical settings, to discuss hip fracture risk. In DM, either type 1 or type 2, fracture risk is elevated probably due to deteriorated bone quality and increased frequency of falls, because the risk is much higher than that expected by bone density. In CKD, especially in patients undergoing dialysis therapy, high risks of fractures in younger people and of mortality after fractures are striking. Even mild to moderate renal dysfunction has recently been reported to elevate fracture risk. In GIO, we reviewed some papers in terms of relationship between doses and duration of corticosteroids and fracture risk.

ステロイド療法により進行を抑えることができたChinese Herbs Nephropathyの1例

The patients was a 43-year-old woman whose chief complaints were nausea and heaviness of the heads. There was a history of toxemia of pregnancy. The patient had previously taken Tenshin Tokishigyaku-ka-goshuyu-shokyo-to for two years because of cold sensitivity. Fever, thirst, and loss of appetite developed from approximately 18 months after she started treatment with the Chinese herbal preparation, and she presented at our outpatient clinic 2.5 years later. On initial examination, deterioration of renal function was evident and the serum creatinine level was 3.4 mg/dl. A renal biopsy specimen showed marked interstitial fibrosis without inflammatory cell infiltration, leading to the diagnosis of Chinese herbs nephropathy (CHN). Steroid therapy was started on the 36th hospital day after a sharp rise in the serum creatinine level to 5.1 mg/dl. This resulted in the rapid improvement of renal function and reduction of the serum creatinine to 2.6 mg/dl by 8 weeks after the initiation of treatment. In a study on the use of steroids for patients with progressive moderate renal dysfunction caused by Chinese herbs, Vanherweghem et al. reported that the progression of renal failure was appreciably slowed in patients given steroids when compared with the control group. We were also able to slow the progression of renal dysfunction in our patient by steroid therapy, although the prognosis of CHN is generally considered to be very poor.

Chronic kidney disease in pregnancy requiring first-time dialysis

Objective To report on the treatment and outcome of pregnancy in 29 women with chronic kidney disease (CKD), 24 of whom had moderate or severe renal dysfunction. Methods Renal dysfunction at the onset of pregnancy was stratified: serum creatinine ≤ 1.4 mg/dL was defined as mild; 1.5–2.5 mg/dL was defined as moderate; and > 2.5 mg/dL was defined as severe renal insufficiency. Clinical complications and perinatal outcomes were evaluated. Results The average serum creatinine level at the beginning of pregnancy was 3.32 mg/dL (range, 1.2–7.1 mg/dL), and the average urine protein level was 1.51 g in 24 hours (range, 0.1–5.6 g in 24 hours). Dialysis therapy was necessary for 1 woman with mild renal dysfunction, 4 patients with moderate renal dysfunction, and 17 patients with severe renal dysfunction. Conclusion The use of dialysis in pregnancy among women with moderate or severe renal dysfunction proved to be useful, but many patients became dependent on dialysis. It is not known whether this was due to the interaction between pregnancy and advanced CKD.

Fibroblast growth factor-23 and mineral metabolism after unilateral nephrectomy

Fibroblast growth factor -23 (FGF-23) is a key regulator of mineral metabolism. It regulates renal phosphate (Pi) reabsorption and calcitriol synthesis, and has an inhibitory effect on parathyroid hormone (PTH) secretion. FGF-23 increases early in chronic kidney disease (CKD), but the regulation of FGF-23 in mild -to -moderate renal dysfunction is not fully understood. Nine healthy kidney donors underwent unilateral nephrectomy. Estimated glomerular filtration rate (eGFR) calculated from cystatin C and parameters of mineral metabolism: (Pi, ionized calcium, biointact PTH, intact FGF-23, calcitriol, and urinary excretion of calcium and Pi) were analysed before surgery, and one day, one week and three to six months after surgery. On the first post-operative day, PTH increased due to a decrease in the calcium level. One week after nephrectomy, the FGF-23 level increased from 31.8 ± 12.3 pg/mL to 55.8 ± 15.1 pg/mL, while PTH, Pi and calcium levels were unchanged compared towith baseline. On follow-up, eGFR improved compared with its one-week value, and PTH and FGF-23 were unchanged compared towith baseline. The calcitriol level decreased but was in the normal range at all points in time. The total amount of Pi in urine did not change, while the calcium excretion decreased significantly. Pi homeostasis after nephrectomy is maintained by PTH on the first day. When serum calcium is stabilized and food intake resumed, FGF-23 rises, possibly in response to the Pi- load in relation to GFR.

5 ASSOCIATION BETWEEN RENAL FUNCTION AND CANCER INCIDENCE IN A LARGE, POPULATION-BASED COHORT

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Evidence-based Medicine & Outcomes I1 Apr 20105 ASSOCIATION BETWEEN RENAL FUNCTION AND CANCER INCIDENCE IN A LARGE, POPULATION-BASED COHORT Anders Christensson, Caroline Savage, Angel Cronin, M. Frank O'Brien, Peter Nilsson, Jonas Manjer, Andrew Vickers, Paul Russo, and Hans Lilja Anders ChristenssonAnders Christensson Malmo, Sweden More articles by this author , Caroline SavageCaroline Savage New York, NY More articles by this author , Angel CroninAngel Cronin New York, NY More articles by this author , M. Frank O'BrienM. Frank O'Brien New York, NY More articles by this author , Peter NilssonPeter Nilsson Malmo, Sweden More articles by this author , Jonas ManjerJonas Manjer Malmo, Sweden More articles by this author , Andrew VickersAndrew Vickers New York, NY More articles by this author , Paul RussoPaul Russo New York, NY More articles by this author , and Hans LiljaHans Lilja New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.048AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are reports that impaired renal function increases the risk of several types of cancer. We evaluated whether moderately impaired renal function influenced risk of developing cancer in a large, population-based cohort. METHODS We used data from Malmö Preventative Medicine Project, a large, population-based cohort (74% participation) containing demographic data and blood samples collected from 33,346 persons aged 33-50 during 1974-86 in Malmö, Sweden. Incident cancers were identified from the Swedish Cancer Registry, updated to 12/31/2006. Glomerular filtration rate (GFR) was estimated using the Modified Diet and Renal Disease formula. Patients were classified as having normal kidney function (GFR≥90 mL/min/1.73m2), mild kidney disease (GFR 60-89 mL/min/1.73m2) or moderate kidney dysfunction (GFR<60 mL/min/1.73m2). We calculated the risk of being diagnosed with cancer using the cumulative incidence function in the presence of a competing risk (death without cancer diagnosis). RESULTS 7,577 patients were diagnosed with cancer and 4,588 died with no cancer diagnosis. The median age at baseline was 47 (IQR 40, 49). 22,183 (69%) participants were male; prostate cancer was the most common cancer diagnosis (n=1,579). Most subjects had mild kidney disease (n=22,336; 70%); 3% (n=1,015) had moderate renal dysfunction and 27% (n=8,621) had normal renal function. The cumulative incidence of cancer was highest for those with the most severely impaired renal function: 20-year cumulative incidence of cancer was 17.3% (95% CI: 15.1%, 19.8%) for those with GFR<60 versus 13.5% (95% CI: 13.0%, 13.9%) and 11.6% (95% CI: 10.9%, 12.3%) for those with GFR 60-89, and ≥90 mL/min/1.73m2, respectively (p<0.001; Figure). This association remained significant after adjustment for age (p<0.001). CONCLUSIONS The mechanism by which cancer risk is associated with renal impairment is unclear but could be due to changes in the accumulation of low molecular mass substances due to decreased GFR. It will be critical to determine which types of cancer are elevated with renal dysfunction. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e2-e3 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anders Christensson Malmo, Sweden More articles by this author Caroline Savage New York, NY More articles by this author Angel Cronin New York, NY More articles by this author M. Frank O'Brien New York, NY More articles by this author Peter Nilsson Malmo, Sweden More articles by this author Jonas Manjer Malmo, Sweden More articles by this author Andrew Vickers New York, NY More articles by this author Paul Russo New York, NY More articles by this author Hans Lilja New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Influence of tonsillectomy on the progression of mesangioproliferative glomerulonephritis

Little information is available about the efficacy of tonsillectomy on long-term renal survival of patients with primary IgA nephropathy (IgAN). In this retrospective cohort study, we considered 61 patients with IgAN who had tonsillectomy (n = 15) or not (n = 46) and compared them with 121 control patients with mesangioproliferative glomerulonephritis (MesGN) free of IgA deposits, who had tonsillectomy (n = 49) or not (n = 72). We evaluated the progression from a normal function [estimated glomerular filtration rate 60-220 mL/min/1.73 m(2), chronic kidney disease (CKD) stage 1 and 2] to a moderate renal dysfunction in CKD stage 3, which was considered the outcome. The mean duration of follow-up was 250 months (12-300 months) in the whole group of 182 patients. The survival to progression to stage 3 was 88% after 10 years, 71% after 20 years and 53% after 25 years. It was 72% after 20 years in both groups. Tonsillectomy was not significantly associated with CKD progression. Significant prognostic factors were age (P = 0.01), initial CKD stage (P = 0.03), proteinuria (P = 0.03), persistent proteinuria (P < 0.001) and diastolic blood pressure (P = 0.01). In the multivariate analysis (Cox model), there was no significant effect of tonsillectomy adjusted for the type of glomerulonephritis, initial CKD stage, persistent proteinuria, diastolic blood pressure and age. Only persistent proteinuria adjusted for the other factors was significantly associated with CKD progression (hazard ratio of 6.2, 95% confidence interval 3.1-12.7, P < 0.001). Tonsillectomy was not associated with a different progression rate of IgAN nor of MesGN after 20 years of follow-up.

Left ventricular mass in hypertensive patients with mild‐to‐moderate reduction of renal function

Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular (CV) morbidity and mortality. The aim of the present study was to evaluate the relationship between LV mass and mild-to-moderate renal dysfunction in a group of non-diabetic hypertensives, free of CV diseases, participating in the Renal Dysfunction in Hypertension (REDHY) study. Patients with diabetes, a body mass index (BMI) of more than 35 kg/m(2), secondary hypertension, CV diseases and a glomerular filtration rate (GFR) of less than 30 mL/min per 1.73 m(2) were excluded. The final sample included 455 patients, who underwent echocardiographic examination and ambulatory blood pressure monitoring. There was a significant trend for a stepwise increase in LV mass, indexed by both body surface area (LVMI) and height elevated to 2.7 (LVMH(2.7)), with the declining renal function, that remained statistically significant after correction for potential confounders. The prevalence of LVH, defined either as LVMI of 125 g/m(2) or more or as LVMH(2.7) of 51 g/m(2.7) or more, was higher in subjects with lower values of GFR than in those with normal renal function (P < 0.001 in both cases). The multiple regression analysis confirmed that the inverse association between GFR and LVM was independent of confounding factors. The present study confirms the high prevalence of LVH in patients with mild or moderate renal dysfunction. In the patients studied (all with a GFR of 30 mL/min per 1.73 m(2)), the association between LVM and GFR was independent of potential confounders, including 24 h blood pressure load. Taking into account the negative prognostic impact of LVH, further studies focusing on a deeper comprehension of the mechanisms underlying the development of LVH in chronic kidney disease patients are needed.

Safe use of radiographic contrast media

Summary injection of iodinated radiographic contrast media is generally safe, however with increased use adverse events are more likely to occur. The most important adverse effects include hypersensitivity reactions, contrast-induced nephropathy and thyrotoxicosis. There is no protocol that will prevent non- ige-mediated anaphylaxis. in patients with moderate renal dysfunction, adequate hydration and use of as little contrast media as practical is recommended. Contrast-induced nephropathy is often transient. Metformin has been associated with lactic acidosis in patients receiving contrast media. it should therefore be discontinued for 48 hours starting on the day of the contrast study. The use of alternative non-iodinated contrast agents, particularly in ultrasound and magnetic resonance, is also growing. Gadolinium magnetic resonance agents have been associated with nephrogenic fibrosing sclerosis in patients with renal dysfunction.

New Drug Approvals: Silodosin for Benign Prostatic Hyperplasia

To review the pharmacology, pharmacokinetics, clinical trials, and safety of silodosin, a recently approved alpha(1A)-adrenergic receptor (AR) antagonist for benign prostatic hyperplasia (BPH). English-only articles obtained from MEDLINE (1966-October 2009) using the search terms silodosin and KMD-3213 were reviewed. In addition, a search of International Pharmaceutical Abstracts (1970-October 2009) was conducted. Available English-language articles were reviewed, as well as abstracts from available non-English articles. Silodosin reduces urinary symptoms associated with BPH in as little as 1 day after initiation. The largest clinical trial conducted to date demonstrated a decrease in International Prostate Symptom Score of -6.4 +/- 6.63 points compared to -3.5 +/- 5.84 in patients receiving placebo (p < 0.0001). Silodosin also improved urinary flow rates by approximately 2.8 +/- 3.44 mL/sec, which is comparable to other alpha(1)-AR antagonists. The usual dose of silodosin is 8 mg once daily and should be reduced to 4 mg for patients with moderate renal dysfunction. Use is contraindicated in patients with severe renal and hepatic impairment or taking strong CYP3A4 inhibitors. In clinical trials, the most prevalent adverse effects were ejaculatory disturbances, occurring in approximately 28% of patients, although only 2.8% of patients discontinued treatment due to this adverse effect. Preliminary data suggest that, similar to other third-generation alpha(1A)-AR antagonists, silodosin has little potential to cause significant cardiovascular adverse effects such as orthostatic hypotension or syncope. To confirm these findings, long-term studies are still needed, especially in patients taking antihypertensive agents and in those with a history of intolerance to other alpha(1)-AR antagonists. Silodosin was approved by the Food and Drug Administration in 2008. Long-term studies demonstrating improvement in clinically important outcomes of BPH have yet to be published. In addition, pharmacoeconomic analyses would assist in defining its current place in therapy. Until this information is available, silodosin may be best reserved as an alternative to other second- and third-generation alpha(1)-AR antagonists.

Ceftaroline fosamil: A novel broad-spectrum cephalosporin

Ceftaroline fosamil is a new extended-spectrum cephalosporin with activity against drug-resistant Grampositive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. At the same time, its Gramnegative spectrum of coverage includes common respiratory pathogens such as Haemophilus influenzae and Moraxella catarrhalis, as well as wild-type Enterobacteriaceae. In vivo efficacy for the treatment of experimental endocarditis, pneumonia, myositis and osteomyelitis has been demonstrated in animal models, while efficacy in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia has been demonstrated in phase II and III clinical trials in humans. The drug is well tolerated and has a low rate of reported adverse events. The dose of ceftaroline fosamil used is 600 mg i.v. every 12 h for patients with normal renal function or mild renal dysfunction. In patients with moderate renal dysfunction, it has been suggested that ceftaroline fosamil be dosed at 400 mg i.v. over 60 min every 12 h. Ceftaroline fosamil is still under review by the U.S. FDA, and when approved, will be one of the first commercially available β-lactams with the ability to treat infections due to MRSA and other drug-resistant Gram-positive pathogens.

Impact of Moderate to Severe Renal Impairment on Mortality and Appropriate Shocks in Patients with Implantable Cardioverter Defibrillators

Background. Due to underrepresentation of patients with chronic kidney disease (CKD) in large Implantable-Cardioverter Defibrillator (ICD) clinical trials, the impact of ICD remains uncertain in this population. Methods. Consecutive patients who received ICD at Creighton university medical center between years 2000–2004 were included in a retrospective cohort after excluding those on maintenance dialysis. Based on baseline Glomerular filtration rate (GFR), patients were classified as severe CKD: GFR < 30 mL/min; moderate CKD: GFR: 30–59 mL/min; and mild or no CKD: GFR ≥ 60 mL/min. The impact of GFR on appropriate shocks and survival was assessed using Kaplan-Meier method and Generalized Linear Models (GLM) with log-link function. Results. There were 509 patients with a mean follow-up of 3.0 + 1.3 years. Mortality risk was inversely proportional to the estimated GFR: 2 fold higher risk with GFR between 30–59 mL/min and 5 fold higher risk with GFR < 30 mL/min. One hundred and seventy-seven patients received appropriate shock(s); appropriate shock-free survival was lower in patients with severe CKD (GFR < 30) compared to mild or no CKD group (2.8 versus 4.2 yrs). Conclusion. Even moderate renal dysfunction increases all cause mortality in CKD patients with ICD. Severe but not moderate CKD is an independent predictor for time to first appropriate shock.

Increment and impairment of adiponectin in renal failure

Patients with chronic renal failure are at high risk of cardiovascular diseases. Previous studies in healthy population showed that hypoadiponectinemia was associated with high cardiovascular disease risk. However, plasma adiponectin (APN) levels are increased in renal dysfunction. Therefore, the clinical significance of plasma APN level in patients with moderate renal dysfunction is controversial. The aim of this study was to determine the change of plasma APN levels in a mouse model of renal failure and the loss of vasculo-protective function of APN in the presence of high cystatin C levels. Subtotal (5/6) nephrectomy was performed in APN-knockout (KO) mice and wild-type (WT) mice. The procedure in WT mice resulted in the significant increase of plasma APN and cystatin C levels. The clearance rate of APN was measured by injecting plasma from WT mice into KO mice. The clearance rate was significantly decreased in subtotal nephrectomized KO mice compared with sham-operated KO mice. Adiponectin protein and mRNA levels in adipose tissue were similar to subtotal nephrectomized and sham-operated mice. In cultured endothelial cells, at a high concentration corresponding to renal failure, cystatin C abolished the suppressive effects of APN on tumour necrosis factor alpha-induced expression of monocyte adhesion molecules. Plasma APN increases in chronic renal failure, at least in part due to low clearance rate. High concentrations of cystatin C abolish the vasculo-protective effect of APN.