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.
27960667
Pre- and postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure.
BP readings that are obtained in the dialysis unit are commonly used to make therapeutic decisions by clinicians and to predict morbidity and mortality by epidemiologists. Dialysis unit BP are also incorporated in the recent guidelines to target BP control. The magnitude of the difference, overestimation or underestimation, and agreement between dialysis unit BP and ambulatory BP (ABP) are unknown. Articles were selected from Medline to identify those that reported both ABP and dialysis unit BP in hemodialysis patients. Bias was calculated as the difference between dialysis unit and the corresponding ABP. Agreement limits between the BP measurement techniques were assessed by pooled SD of the difference using Bland-Altman methods. Predialysis systolic BP generally overestimated ABP by a variable amount. The heterogeneity between BP measurements did not allow for pooling of the estimates. The agreement limits between the two BP was 41.7 to -25.2 mmHg. Predialysis diastolic BP also generally overestimated the ABP with wide agreement limits (23.7 to -18.9 mmHg). In contrast, postdialysis BP underestimated average ABP with wide agreement limits for both postdialysis systolic BP (33.1 to -36.3 mmHg) and diastolic BP (19.3 to -23.9 mmHg). Dialysis unit BP measurements are imprecise estimates of ABP. Better methods are needed for the assessment of BP in hemodialysis patients for clinical decision making.
35998479
Exploring the paradoxical relationship of hypertension with mortality in chronic hemodialysis.
Hypertension is seen in 85% of patients on hemodialysis (HD) in the United States. Although it is amply clear that high blood pressure (BP) has a continuous, graded, and etiologically significant relationship with cardiovascular outcomes in the general population, studies in HD patients have found an inverse relationship between high BP and outcomes. Thus, those patients with high BP have a lower mortality compared to those with low BP. It is intellectually troublesome to find such an association because high BP, which was such an important risk factor for cardiovascular disease before onset of dialysis suddenly, becomes a protective factor. In patients with chronic kidney disease who are not yet on HD, we strive to lower BP more aggressively than what we target those with uncomplicated essential hypertension. If these observations—‘‘reverse epidemiology’’ or ‘‘risk factor paradox’’—are etiologically significant, should we be complacent about treating high BP in HD? The objective of this analysis is to review the data to explain these apparently troublesome observations. POOR ASSESSMENT OF BP: REGRESSION DILUTION BIAS
28746093
Reproducibility of Renal Function Measurements in Adult Men with Diabetic Nephropathy: Research and Clinical Implications
Background/Aim: Measurement of the renal function is critical to follow progression of kidney disease. Short-term and long-term variabilities in these measurements have significant impacts on clinical decision making and clinical trials. The goal of this study was to describe the variability in these measurements and to calculate minimum sample size estimates over varying time frames for clinical trials. Methods: We studied 44 elderly men with diabetic nephropathy who participated in a clinical trial. Glomerular filtration rate and renal plasma flow were measured by continuous infusion technique with five urine collection periods on two occasions 4 months apart. Protein and creatinine excretion rates were measured in the same specimens. In addition, two consecutive 24-hour specimens every month for 4 months were collected to analyze urine protein, creatinine, urea nitrogen, and electrolytes. A hierarchical random effects model was used to analyze the reproducibility from hour to hour, from day to day, and from month to month. Results: A total of 824 urine specimens were analyzed, of which 412 constituted specimens collected in the short term and 412 were 24-hour urine collections. Hour-to-hour variation accounted for 45% for urinary clearance of iothalamate, but for only 0.5% of the variability in plasma clearance of iothalamate. Day-to-day variability in 24-hour urinary excretion rates for creatinine was 46% and for protein 10%. Month-to-month variability in 24-hour excretion rates for creatinine was 11% and for protein 19%. The urine protein/creatinine ratio had a day-to-day variability of 2% and a month-to-month variability of 19%. Sample size requirements can be reduced by correcting for urine creatinine for some but not all urinary analytes. Conclusions: In nephrotic men with diabetic nephropathy, the coefficient of variation in the month-to-month protein excretion rate is 36%. Approximately 28 patients in each arm of two groups are needed to detect a difference in protein excretion rate of 28% (1 g/day in this study). The coefficient of variation in plasma iothalamate clearance over 4 months is 16%. To detect a 10% change in glomerular filtration rate between two groups, 44 patients per group are needed. To be deemed statistically significant, a change in daily protein excretion rate of at least 72% over month(s) is needed in individual patients.
40070884
Relative plasma volume monitoring for identifying volume-sensitive and -resistant hypertension.
The measurement and management of volume state among long-term dialysis patients has not received much attention. Recent reports suggest that relative plasma volume monitoring may be useful in identifying patients who have volume excess. Among patients who have evidence of excess volume by relative plasma volume monitoring, excess volume removal leads to improvement in interdialytic ambulatory blood pressure. Implementation of this technique can result in improved classification of patients into volume-sensitive and -resistant categories and therefore improve the management of hypertension.
46503631
ACP Journal Club. Urine dipstick readings ≥ 1+ had limited sensitivity but high specificity for detecting albuminuria in adults.
20354418
Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients.
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is a disease that presents with diverse clinicoradiologic manifestations. High-attenuation mucus (HAM) is a characteristic radiologic finding seen in patients with ABPA; however, the clinical significance of the entity remains unknown.


AIMS AND OBJECTIVES
To describe the outcome of patients with ABPA who were demonstrated to have HAM, and compare with the outcome of patients without HAM.


METHODS
All consecutive patients with asthma presenting to the Chest Clinic of this institute over a 4-year period were screened with an Aspergillus skin test. Patients with positive findings were further investigated, and the diagnosis of ABPA was confirmed based on predefined criteria. The patients were further classified into two groups based on the presence of HAM on HRCT scan.


RESULTS
During the study period, 755 patients were screened for ABPA using the Aspergillus skin test; 291 patients (38.5%) had positive findings, and ABPA was diagnosed in 155 patients (mean age, 33.98 years; 76 women). Twenty-nine patients (18.7%) with ABPA were identified to have HAM on HRCT scans at presentation. The baseline characteristics were similar between the two groups, but patients with HAM had higher mean eosinophil counts, higher mean serum total IgE, and higher Aspergillus fumigatus-specific IgE levels. On multivariate analysis, both the severity of bronchiectasis and HAM predicted relapse of ABPA (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.13 to 1.42; and OR, 3.61; 95% CI, 1.23 to 10.61, respectively). Failure to achieve complete remission was influenced by the severity of bronchiectasis but not by HAM (OR, 1.55; 95% CI, 1.29 to 1.85; and OR, 3.41; 95% CI, 0.89 to 13.1, respectively).


CONCLUSIONS
HAM impaction in ABPA is associated with initial serologic severity and frequent relapses but does not seem to influence complete remission.
23395637
Clinical relevance of peripheral blood eosinophil count in allergic bronchopulmonary aspergillosis.
BACKGROUND AND AIMS
Currently, there is not a uniform consensus regarding the number of criteria or specific cut-off values for the variety of tests that are used to diagnose allergic bronchopulmonary aspergillosis (ABPA). Traditionally, an eosinophil count >1000 cells/μl is considered an important criterion in the diagnosis of ABPA. The goal of this study was to delineate the significance of the peripheral blood eosinophil count in the diagnosis of ABPA, and the relationship between eosinophil counts and lung function and immunological and radiological parameters.


METHODS
This study was a retrospective analysis of the data from ABPA patients who were managed in our chest clinic. Based on their eosinophil count, the patients were classified into the following three categories: <500, 500-1000 and >1000 cells/μl. The spirometric, immunological and radiological characteristics were also assessed.


RESULTS
We studied 108 males and 101 females with a combined mean (±SD) age of 34.1±12.5years. The median (IQR) eosinophil count at diagnosis was 850 (510-1541)cells/μl, and 60% of the patients had an eosinophil count of <1000 cells/μl. We found no relationship between eosinophil count and lung function using spirometry and other immunological parameters. The median eosinophil count was higher in patients with an high resolution computed tomography (HRCT) chest finding of bronchiectasis (986 vs. 620, p<0.001) vs. those without and in patients with high-attenuation mucus (1200 vs. 800, p<0.001) compared to those without high-attenuation mucus.


CONCLUSIONS
A peripheral blood eosinophil count has limited utility in the diagnosis of ABPA, and there is no relationship between eosinophil count and lung function or other immunological parameters. The higher eosinophil count that we observed in patients with central bronchiectasis or high-attenuation mucus suggests that eosinophils are primary mediators of inflammatory activity in ABPA.
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.
37563683
High-attenuation mucus in allergic bronchopulmonary aspergillosis: another cause of diffuse high-attenuation pulmonary abnormality.
24077597
Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria.
Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis. There are estimated to be in excess of four million patients affected world-wide. The importance of recognizing ABPA relates to the improvement of patient symptoms, and delay in development or prevention of bronchiectasis, one manifestation of permanent lung damage in ABPA. Environmental factors may not be the only pathogenetic factors because not all asthmatics develop ABPA despite being exposed to the same environment. Allergic bronchopulmonary aspergillosis is probably a polygenic disorder, which does not remit completely once expressed, although long-term remissions do occur. In a genetically predisposed individual, inhaled conidia of A. fumigatus germinate into hyphae with release of antigens that activate the innate and adaptive immune responses (Th2 CD4(+) T cell responses) of the lung. The International Society for Human and Animal Mycology (ISHAM) has constituted a working group on ABPA complicating asthma (www.abpaworkinggroup.org), which convened an international conference to summarize the current state of knowledge, and formulate consensus-based guidelines for diagnosis and therapy. New diagnosis and staging criteria for ABPA are proposed. Although a small number of randomized controlled trials have been conducted, long-term management remains poorly studied. Primary therapy consists of oral corticosteroids to control exacerbations, itraconazole as a steroid-sparing agent and optimized asthma therapy. Uncertainties surround the prevention and management of bronchiectasis, chronic pulmonary aspergillosis and aspergilloma as complications, concurrent rhinosinusitis and environmental control. There is need for new oral antifungal agents and immunomodulatory therapy.