24112706
A Randomized Controlled Trial of Oral versus Intravenous Iron in Chronic Kidney Disease
Background: It is unknown whether intravenous iron or oral iron repletion alone can correct anemia associated with chronic kidney disease (CKD). We conducted a randomized multicenter controlled trial in adult anemic, iron-deficient non-dialysis CKD (ND-CKD) patients (≧stage 3) not receiving erythropoiesis-stimulating agents (ESAs). Methods: The participants were randomized to receive either a sodium ferric gluconate complex (intravenous iron) 250 mg i.v. weekly × 4 or ferrous sulfate (oral iron) 325 mg t.i.d. × 42 days. Hemoglobin (Hgb), ferritin and transferrin saturation (TSAT) were measured serially, and the Kidney Disease Quality of Life (KDQoL) questionnaire was administered on days 1 and 43. The primary outcome variable was change from baseline (CFB) to endpoint in Hgb values. Results: Seventy-five patients were analyzed (intravenous iron n = 36, oral iron n = 39). CFB in Hgb was similar in the two groups (intravenous iron 0.4 g/dl vs. oral iron 0.2 g/dl, p = n.s.). However, the increase in Hgb was only significant with intravenous iron (p < 0.01). In comparison to oral iron, intravenous iron achieved greater improvements in ferritin (232.0 ± 160.8 vs. 55.9 ± 236.2 ng/ml, p < 0.001) and TSAT (8.3 ± 7.5 vs. 2.9 ± 8.8%, p = 0.007). Intravenous iron caused greater improvements in KDQoL scores than oral iron (p < 0.05). The most common side effect reported with intravenous iron was hypotension, while constipation was more common with oral iron. Conclusions: Oral and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD patients not receiving ESAs. Although in comparison to oral iron, intravenous iron may result in a more rapid repletion of iron stores and greater improvement in quality of life, it exposes the patients to a greater risk of adverse effects and increases inconvenience and cost.
11453581
Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade.
Oxidative stress plays an important role in causing progressive chronic kidney disease (CKD). We examined the influence of add-on ANG II receptor blockade administered as losartan (50 mg/day for 1 mo) on oxidative stress and proinflammatory state of the kidney in patients with CKD. All subjects were taking an angiotensin-converting enzyme inhibitor plus other antihypertensive agents. Oxidative stress to lipids and proteins was measured by an HPLC assay for malondialdehyde (MDA) and carbonyl concentration, respectively. Urinary inflammation was measured by monocyte chemotactic protein-1 (MCP-1) excretion rate. The etiology of CKD was type 2 diabetes mellitus in 12 and glomerulonephritis in 4 patients. There was no change in proteinuria or 24-h ambulatory blood pressure (BP) with add-on ANG II receptor blockade with losartan therapy. Before losartan therapy, urinary protein and albumin oxidation were 99 and 71% higher, respectively, compared with in plasma (P < 0.05). There was a 35% reduction in urinary oxidized albumin with add-on losartan therapy (P = 0.036). Urinary and plasma MDA were elevated compared with age-matched controls. Urinary MDA was significantly reduced from 4.75 +/- 3.23 to 3.39 +/- 2.17 micromol/g creatinine with add-on losartan therapy. However, plasma MDA or oxidized proteins did not change in response to additional ANG II blockade. A good correlation was seen between the change in urinary oxidized albumin and MCP-1 levels (r = 0.61, P = 0.012). These data demonstrate that oxidative damage to urinary protein and lipids can be reduced with additional ANG II receptor blockade, independently of reductions in proteinuria or BP. Urinary measurements of markers of oxidative damage to lipids and proteins appear to be more sensitive than plasma measurements in patients with CKD. The significant association of the change in urinary MCP-1 with a reduction in oxidative stress supports the role of the redox state in the kidney with renal fibrosis and progressive kidney damage.
36005104
Volume Overload in Dialysis: The Elephant in the Room, No One Can See
interests of the authors. However, considering the totality of the evidence, I am less convinced that this marker is superior to other volume markers. First, there are few head-to-head studies comparing BIA to other established markers of volume. Second, there is no range that defines ‘normal’. Unlike blood pressure (BP) or cholesterol, there is no target that has been established. The normal values are obtained from healthy subjects whose body composition differs substantially from those on dialysis. Extrapolating from healthy subjects to those with ESRD on hemodialysis does not appear scientifically valid. Third, there is no study to my knowledge that demonstrates convincingly that compared to probing dry weight without BIA, BIA-guided dry weight reduction results in improved outcomes. Most data provided to support the use of BIA are associative and observational. A large amount of observational data does not prove causation. We therefore have to be cautious in interpreting these data as ‘strongly indicative of fluid overload’. Nearly all markers of volemia suffer from the same shortcomings. These shortcomings include lack of normative data, and data being largely observational and associative in nature. As an example, several observational studies suggest that B-type natriuretic peptide (BNP), NT-proBNP or other natriuretic peptides are associated with volume state among people with ESRD on dialysis [2–10] . However, only one study has been reported to date that relates the change in BNP to an intervention of probing dry weight [11] . In this study, a direct relationship existed at baseline between BNP and interdialytic ambulatory BP. Since interdialytic ambulatory BP is reVolume overload is the invisible threat to the health of dialysis patients. Currently, Medicare incentivizes the measurement of the dose of dialysis (urea reduction ratio) but has no measure of volume. Perhaps this is because the few who can recognize the epidemic nature of volume excess cannot agree on how to define it. Whereas, some have proposed interdialytic weight gain (IDWG) as a marker of volume, the in-depth review of Hecking et al. [1] quite clearly and importantly makes the distinction that IDWG should not be confused with hypervolemia. One has to wonder how IDWG got confused with dry weight in the first place. It appears that epidemiologists decided to use IDWG as a proxy of dry weight because of its ready availability in large databases. IDWG is a marker that is convenient; it can be measured easily and it can be related to outcomes such as all-cause mortality. This analysis was performed and a relationship emerged between IDWG and all-cause mortality. But establishing a relationship between IDWG and mortality does not establish causality. It could be numerous other factors, measured and unmeasured, associated with IDWG which may be causally related to mortality. Factors such as missing or cutting short dialysis, not taking medications as prescribed, and consuming a diet rich in phosphorus and potassium are some confounding factors that may also be associated with IDWG but may be more plausibly related to mortality. The authors discuss several markers of volume excess. Although several exist, one marker, bioimpedance analysis (BIA), is discussed in great detail. This is understandable given both the academic and intellectual property Published online: July 6, 2013 Nephrology American Journal of
24249726
Regulation of circadian blood pressure: from mice to astronauts.
PURPOSE OF REVIEW
Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of blood pressure (BP) has been shown to be associated with greater target organ damage and with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP.


RECENT FINDINGS
The time-keeper in mammals resides centrally in the suprachiasmatic nucleus. Apart from this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice with the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon three major factors: physical activity, autonomic function, and sodium sensitivity.


SUMMARY
The integrated consideration of physical activity, autonomic function, and sodium sensitivity appears to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts.
191311
Assessment of iothalamate plasma clearance: duration of study affects quality of GFR.
BACKGROUND AND OBJECTIVES
Measurement of GFR is important for the management of chronic kidney disease (CKD). Although bolus administration of radiocontrast agents is commonly used to measure GFR, the optimal duration of sampling to assess their plasma clearance is unknown. The purpose of this study was to evaluate whether the duration of plasma sampling influences precision and estimation of GFR.


DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
GFR was measured by sampling plasma 12 times over 5 h in 56 patients with CKD (mean age 64 yr, 98% men, 79% Caucasian, 34% diabetics, estimated GFR 31.8 +/- 14.2 ml/min/1.73 m(2)). In a subset of 12 patients we measured GFR by sampling plasma 17 times over 10 h.


RESULTS
Short sampling intervals considerably overestimated GFR measured using total plasma iothalamate clearance, especially in larger patients. In the higher estimated GFR group (>30 ml/min/1.73 m(2)), the 5-h GFR was 17% higher and 2-h GFR 54% higher compared with the 10-h GFR, which averaged 40.3 ml/min/1.73 m(2). In the lower estimated GFR group (<30 ml/min/1.73 m(2)), the 5-h GFR was 36% higher and 2-h GFR 126% higher compared with the 10-h GFR, which averaged 22.2 ml/min/1.73 m(2). Short sampling duration also reduced the precision of the estimated GFR from 1.67% for 10-h GFR, to 3.48% for 5-h GFR, and to 7.07% for 2-h GFR.


CONCLUSIONS
GFR measured over a longer duration with multiple plasma samples spanning the distribution and elimination phases may improve precision and provide a better measure of renal function.
22176722
Alar web in cleft lip nose deformity: study in adult unilateral clefts.
BACKGROUND
The correction of alar webbing in unilateral cleft lip nose deformity is challenging because of progressive distortions in the alar web region during the period of growth. Alar webbing is a persistent universal deformity in both the primary and secondary cleft lip noses. The purpose of this article is to study the alar web deformity in adult patients with unilateral cleft lip noses.


METHODS
Twenty-five patients aged 13 years and older presenting with unilateral cleft nasal deformity were included. Preoperative and postoperative measurements of the nose, along with detailed intraoperative recording of the deformed anatomy, were done. Preoperative magnetic resonance imaging was also done in selected cases. Transcolumellar open rhinoplasty was performed in all the cases, and nasal septal straightening with centralization was done. Cleft alar base augmentation was done using bone graft to restore symmetry of the nasal tripod. Both the cleft and noncleft alar cartilages were extensively mobilized from the skin and mucosal sides. The overgrown and caudally slumped cleft-side alar cartilage was resected caudally and was then resuspended in a symmetrical position with the noncleft alar cartilage. A midline-strut septal cartilage extension graft was used to restore the tip aesthetics. The skin overlying the alar web was in-rolled after semilunar cartilage resection, and skin excision was also done to restore symmetry with the opposite vestibule. The remaining secondary cleft nasal and lip deformities were corrected depending upon the specific presenting pathologic abnormality.


RESULTS
The cleft alar cartilage was found to be caudally displaced in all the cases. The caudal border of the lateral crus was prolapsing in the cavity of the vestibule on the superomedial aspect and was tenting the skin in the area of the weak triangle, producing the characteristic alar web deformity. In the study group, the maximum width of the cleft alar cartilage at the level of the lateral crus was increased by approximately 4 mm when compared with the noncleft alar cartilage. The before- and after-rhinoplasty surgery results were objectively assessed using a patient, surgeon, and independent observer survey. The cosmetic result of the nasal tip complex was found to be very good and good (90%), satisfactory (5%), and poor (5%) in patients.


CONCLUSIONS
The alar web in unilateral cleft lip nose deformity is the result of caudal overgrowth and migration of the alar cartilage. The caudal edge of the prolapsed lateral crus overhangs the cleft-side nasal aperture on its superomedial aspect, producing this deformity. Satisfactory correction of this deformity should envisage caudal resection and repositioning of the dislocated alar cartilage along with caudal resection of the lateral crus with in-rolling of the skin after resection to achieve symmetric results in unilateral cleft lip rhinoplasty.
13914994
Noninvasive positive pressure ventilation in acute respiratory failure due to COPD vs other causes: Effectiveness and predictors of failure in a respiratory ICU in North India
Objectives To determine the effectiveness of noninvasive positive pressure ventilation (NIPPV), and the factors predicting failure of NIPPV in acute respiratory failure (ARF) due to chronic obstructive pulmonary disease (COPD) versus other causes of ARF. Patients and methods This was a prospective observational study and all patients with ARF requiring NIPPV over a one-and-a-half year period were enrolled in the study. We recorded the etiology of ARF and prospectively collected the data for heart rate, respiratory rate, arterial blood gases (pH, partial pressure of oxygen in the arterial blood [PaO2], partial pressure of carbon dioxide in arterial blood [PaCO2]) at baseline, one and four hours. The patients were further classified into two groups based on the etiology of ARF as COPD–ARF and ARF due to other causes. The primary outcome was the need for endotracheal intubation during the intensive care unit (ICU) stay. Results During the study period, 248 patients were admitted in the ICU and of these 63 (25.4%; 24, COPD–ARF, 39, ARF due to other causes; 40 male and 23 female patients; mean [standard deviation] age of 45.7 [16.6] years) patients were initiated on NIPPV. Patients with ARF secondary to COPD were older, had higher APACHE II scores, lower respiratory rates, levels compared to other causes of ARF. After one hour there was lower pH and higher PaCO2 levels with increase a significant decrease in respiratory rate and heart rate and decline in PaCO2 levels in patients successfully managed with NIPPV. However, there was no in pH and PaO2 difference in improvement of clinical and blood gas parameters between the two groups except at one hour which was significantly the rate of decline of pH at one and four hours and PaCO2 faster in the COPD group. NIPPV failures were significantly higher in ARF due to other causes (15/39) than in ARF–COPD (3/24) (p = 0.03). The mean ICU and hospital stay and the hospital mortality were similar in the two groups. In the multivariate logistic regression model (after and adjusting for gender, APACHE II scores and improvement in respiratory rate, pH, PaO2 at one hour) only the etiology of ARF, ie, ARF–COPD, was associated with a decreased PaCO2 risk of NIPPV failure (odds ratio 0.23; 95% confidence interval, 0.58–0.9). Conclusions NIPPV is more effective in preventing endotracheal intubation in ARF due to COPD than other causes, and the etiology of ARF is an important predictor of NIPPV failure.
39024721
Efficacy and safety of iodopovidone in chemical pleurodesis: a meta-analysis of observational studies.
The search for an 'ideal' agent for pleurodesis continues. Iodopovidone is a topical antiseptic and has been shown to be safe and effective in many studies. The aim of this study was to evaluate the efficacy and safety of iodopovidone as an agent for chemical pleurodesis. We performed a systematic review of all the observational trials which have used iodopovidone for chemical pleurodesis. Six studies including 265 patients who had undergone chemical pleurodesis with iodopovidone were included for this analysis. Iodopovidone was used for variety of indications, which included pleural effusion (157 patients), and pneumothorax (108 patients). Pleurodesis was performed through tube thoracostomy in 144 patients and through thoracoscopy in 121 patients. The success rate of pleurodesis varied from 64.2% to 100%, and summary success rate of all the studies was 90.6% (95% confidence intervals [CI], 86.4-93.8). The success rate was independent for the procedure (tube thoracostomy [126/144; 87.5%, 95% CI 80.9-92.4] or thoracoscopy [114/121; 94.2%, 95% CI 88.4-97.6]) used for performing pleurodesis or for the indication (pleural effusion [139/157; 88.5%, 95% CI 82.5-93.1] or pneumothorax [101/108; 93.5%, 95% CI 87.1-97.4]). The only significant complication reported was chest pain of varying degree. Systemic hypotension was reported in three patients in only one study. There were no deaths related to chemical pleurodesis with iodopovidone. Overall, this review supports the safety and efficacy of iodopovidone as an agent for chemical pleurodesis in cases of recurrent pleural effusions and pneumothoraces regardless of their etiology.
23113580
Future Target Molecules in Antiglaucoma Therapy: TGF-β May Have a Role to Play
Glaucoma, a leading cause of irreversible blindness, is often associated with increased resistance to aqueous outflow in trabecular tissue. Increased outflow resistance has been attributed to increased extracellular matrix (ECM) deposition in trabecular tissue. A critical balance between the synthesis and breakdown of the components of extracellular tissue is important in keeping the intraocular pressure within the normal range. Multiple mechanisms have been shown to affect ECM turnover in trabecular tissue. In this review, we examine the related literature to understand the role of TGF-β in ECM turnover, in the development and progression of glaucoma, and in possible therapeutic strategies that can be devised by targeting the TGF-β signaling pathways.
24800503
Clinical significance of Aspergillus sensitisation in bronchial asthma.
Numerous studies have suggested a link between fungal sensitisation and severity of asthma. However, few studies have specifically evaluated the relationship between Aspergillus sensitisation and asthma severity. This study was aimed at investigating the clinical significance of Aspergillus sensitisation in asthma. In this prospective cross-sectional study, patients with asthma were subjected to pulmonary function test and an intradermal Aspergillus skin test (AST) apart from a detailed clinical history and physical examination. Assessment of asthma severity was carried according to the Global Initiative for Asthma (GINA) recommendations, Asthma Control Test (ACT) and the mini Asthma Quality of Life Questionnaire (mini AQLQ). Based on AST, the cases were dichotomised into Aspergillus-sensitive and AST-negative groups. There were 417 (193 males, 224 females; mean age, 34 years) asthmatic patients of whom 219 (52.5%) showed Aspergillus sensitisation. The severity of disease as per the GINA criteria and the dose of ICS required for asthma control were similar in the two groups. The Aspergillus-sensitive group had poorer pulmonary function than the AST-negative group [AST positive vs. negative: percentage predicted mean (SD) forced expiratory volume in the first second: 73.1(23.8) vs. 77.9(22.7), P = 0.04; mean (SD) FEV(1) /forced vital capacity (FVC) ratio: 68.2(13.3) vs. 74.3(15.7), P = 0.0001]. The mini AQLQ scores were similar in the two groups. In the ACT, the numbers of patients in the domain pertaining to nocturnal awakenings were significantly higher in the Aspergillus-sensitive group (P = 0.014). There was a weak association between Aspergillus sensitisation and severity of asthma. Whether Aspergillus sensitisation is causally linked to asthma severity remains to be seen.
10815047
Metabolism of benzo[a]pyrene by human melanocytes in culture.
Benzo[a]pyrene (B[a]P) is a ubiquitous environmental pollutant and known skin carcinogen. In the present study, in vitro addition of [3H]B[a]P to normal human melanocytes in culture, isolated from adult human skin, resulted in the metabolism of [3H]B[a]P both intracellularly and extracellularly. HPLC analysis showed that [3H]B[a]P-9,10- and 7,8-diol were the major intracellular and extracellular metabolites followed by 3,6-quinone, 9-hydroxy and 3-hydroxy metabolites. Significant amounts of the [3H]B[a]P metabolites were found to be present in the sonicated cell suspension and culture medium as the glucuronide and sulfate conjugates. In total 37.3% of the [3H]B[a]P added in the culture medium was metabolized by melanocytes, of which 21.1% was quantified as the intracellular and 16.2% as the extracellular metabolites. Our data show that human melanocytes are capable of metabolizing B[a]P.