Stimulated whole-blood cytokine/chemokine responses are associated with interstitial cystitis/bladder pain syndrome phenotypes and features of nociplastic pain: a multidisciplinary approach to the study of chronic pelvic pain research network study.

ABSTRACT: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the multidisciplinary approach to the study of chronic pelvic pain research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex vivo toll-like receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS. Here, we attempt to confirm these findings in the multisite multidisciplinary approach to the study of chronic pelvic pain Symptom Patterns Study using TLR4-stimulated whole blood (female IC/BPS patients with COPC n = 99; without n = 36). Samples were collected in tubes preloaded with TLR4 agonist, incubated for 24 hours, and resulting supernatant assayed for 7 cytokines/chemokines. These were subject to a principal components analysis and the resulting components used as dependent variables in general linear models. Controlling for patient age, body mass index, and site of collection, we found that greater ex vivo TLR4-stimulated cytokine/chemokine release was associated with the presence of COPCs ( P < 0.01), extent of widespread pain ( P < 0.05), but not experimental pain sensitivity ( P > 0.05). However, a second component of anti-inflammatory, regulatory, and chemotactic activity was associated with reduced pain sensitivity ( P < 0.01). These results confirm that the IC/BPS + COPCs subtype show higher levels of ex vivo TLR4 cytokine/chemokine release and support a link between immune priming and nociplastic pain in IC/BPS.

Degradation of chlorinated solvents with reactive iron minerals in subsurface sediments from redox transition zones.

Reactive iron (Fe) mineral coatings found in subsurface reduction-oxidation transition zones (RTZs) contribute to the attenuation of contaminants. An 18.3-m anoxic core was collected from the site, where constituents of concern (COCs) in groundwater included chlorinated solvents. Reactive Fe mineral coatings were found to be abundant in the RTZs. This research focused on evaluating reaction kinetics with anoxic sediments bearing ferrous mineral nano-coatings spiked with either tetrachloroethylene (PCE), trichloroethylene (TCE), or 1,4-dichlorobenzene (1,4-DCB). Reaction kinetics with RTZ sediments followed pseudo-first-order reactions for the three contaminants with 90% degradation achieved in less than 39 days. The second-order rate constants for the three COCs ranged from 6.20 × 10-4 to 1.73 × 10-3 Lg-1h-1 with pyrite (FeS2), 4.97 × 10-5 to 1.24 × 10-3 Lg-1h-1with mackinawite (FeS), 1.25 × 10-4 to 1.89 × 10-4 Lg-1h-1 with siderite (FeCO3), and 1.79 × 10-4 to 1.10 × 10-3 Lg-1h-1 with magnetite (Fe3O4). For these three chlorinated solvents, the trend for the rate constants followed: Fe(II) sulfide minerals > magnetite > siderite. The high reactivity of Fe mineral coatings is hypothesized to be due to the large surface areas of the nano-mineral coatings. As a result, these surfaces are expected to play an important role in the attenuation of chlorinated solvents in contaminated subsurface environments.

Longitudinal Changes in the Pelvic Pain Only and Widespread Pain Phenotypes Over One Year in the MAPP-I Urologic Chronic Pelvic Pain Syndrome (UCPPS) Cohort.

OBJECTIVE: To examine how often urologic chronic pelvic pain syndrome (UCPPS) patients progressed from Pelvic Pain Only at baseline to Widespread Pain, or vice versa, during 1-year longitudinal follow-up. METHODS: Men and women with UCPPS enrolled in the MAPP-I Epidemiology and Phenotyping Study completed a self-report body map to indicate their locations of pain every 2 months over 12 months. Patients were categorized at each assessment into one of three pain phenotypes: (1) Pelvic Pain Only, (2) an Intermediate group, (3) Widespread Pain. Only patients who completed 3 or more follow-ups were included in this longitudinal analysis. The primary outcome measure was pain classification at the majority (≥60%) of follow-up assessments. Longitudinal trends of somatic symptom burden were also assessed. RESULTS: Among the 93 UCPPS participants with Pelvic Pain Only at baseline, only 2% (n = 2) showed a Widespread Pain phenotype for the majority of assessments over 12 months. Among the 121 participants who had Widespread Pain at baseline, 6% (n = 7) demonstrated Pelvic Pain Only for the majority of assessments over 12 months. Over half of participants (≥53%) stayed in their baseline phenotypic group. Somatic symptom burden remained stable over 12 months for each of the groups with high intra-class correlation coefficient (0.67 to 0.82). CONCLUSION: It was uncommon for UCPPS patients to progress from Pelvic Pain Only to Widespread Pain, or vice versa, over 12 months. These data suggest that Pelvic Pain Only and Widespread Pain are distinct UCPPS phenotypes that are relatively stable over 12 months of follow up.

Roles of reactive iron mineral coatings in natural attenuation in redox transition zones preserved from a site with historical contamination.

In this study, a protocol was developed to identify reduction-oxidation (redox) transition zones in an effort to exploit natural source zone depletion processes. A sediment core with a total length of 18-m was collected from a site with historical contamination that includes chlorinated benzenes where the redox condition was preserved. In the four redox transition zones investigated, reactive iron coatings are characterized with a suite of analyses under anaerobic conditions. To distinguish surface coating mineralogy, X-ray diffraction, X-ray fluorescence, and field-emission scanning electron microscopy with an energy dispersive X-ray analyzer were applied along with a six-step sequential extraction process. The cycling of Fe and S, as an important contribution and indicator of ongoing natural attenuation processes for constituents of concern (COC), was delineated by using data from multiple and complementary analyses for isolating and identifying iron phases. Along with groundwater chemistry, contaminant concentrations, and microbial genera, attenuation of COCs is expected to be active and sustainable in redox transition zones, where there is an abundance of reactive iron mineral coatings cycling through biogeochemical reactions. Reactions in other redox transition zones may be limited where iron mineral coatings are not dominant.

Impacts of cryogenic sampling processes on iron mineral coatings in contaminated sediment.

This study focused on comparing iron mineral coatings found in contaminated sediments from a cryogenic (Cryo Core) core versus an Anaerobic Core (collected under oxygen-free and ambient conditions). After thawing the Cryo Core in an oxygen-free glovebox, a suite of analyses was applied on sediments from both cores: pH, redox potential, X-ray fluorescence (XRF), X-ray diffraction (XRD), and field-emission scanning electron microscopy (FESEM) with energy dispersive X-ray analyzer (EDX). Among the iron minerals identified, crystalline pyrite was found throughout the Cyro Core sediment samples, which is in contrast to that observed for the Anaerobic Core. Moreover, mackinawite and greigite that were ubiquitous in the Anaerobic Core were not observed in Cryo Core samples. To better understand why the metastable minerals were not present, a freeze/thaw process was simulated on Anaerobic Core samples using a liquid­nitrogen quench with surface coatings characterized by FESEM/EDX. In these quenched samples, mackinawite was no longer observed, and in its place was pyrite. In addition, both greigite and pyrite were found to be unique morphologically after quenching. Dissolution and re-precipitation of iron sulfide coatings during the freeze/thaw process appears to affect the geochemistry of the pore water through two main mechanisms of freeze-concentration and freezing potential.

Association of Longitudinal Changes in Symptoms and Urinary Biomarkers in Patients with Urological Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.

PURPOSE: We analyzed a series of novel noninvasive urinary biomarkers for their ability to objectively monitor the longitudinal clinical status of patients with urological chronic pelvic pain syndrome. MATERIALS AND METHODS: Baseline, 6 and 12-month urine samples were collected (216) and used to quantify vascular endothelial growth factor, vascular endothelial growth factor (VEGF) receptor 1 (R1), neutrophil gelatinase associated lipocalin (NGAL), matrix metalloproteinase-2, matrix metalloproteinase (MMP)-9, and MMP-9/NGAL complex by enzyme-linked immunosorbent assays. Patient symptom changes were classified as improved, stable or worse using a functional clustering algorithm. Proportional odds models were used to evaluate the association between symptom change and urinary biomarkers. RESULTS: Across all sampled participants, longitudinal decreases in normalized VEGF concentration (pg/µg) were associated with pain severity improvement, and decreases in MMP-9, NGAL and VEGF-R1 concentration (pg/ml) as well as NGAL normalized concentration were associated with improved urinary symptoms. Longitudinal decreases in normalized VEGF-R1 were associated with pain improvement in patients with moderate widespreadness, no bladder symptoms and no painful filling. Lower baseline normalized VEGF-R1 concentration was associated with pain improvement in patients with pelvic pain only. Higher baseline MMP-9/NGAL levels were associated with pain and urinary improvement across all participants. Moreover, longitudinal increases in MMP-2 concentration was associated with improved pain in men and patients with painful filling. CONCLUSIONS: Our results suggest these urinary biomarkers may be useful in monitoring urological chronic pelvic pain syndrome symptom changes with respect to both urinary severity and pain severity. With further testing, they may represent objective biological measures of urological chronic pelvic pain syndrome progression and/or resolution while also providing insight into the pathophysiology of urological chronic pelvic pain syndrome.

Identifying redox transition zones in the subsurface of a site with historical contamination.

Reactive iron mineral coatings found throughout reduction-oxidation (redox) transition zones play an important role in contaminant transformation processes. This research focuses on demonstrating a process for effectively delineating redox transition zones at a site with historical contamination. An 18.3 meter core was collected, subsampled, and preserved under anoxic conditions to maintain its original redox status. To ensure a high vertical resolution, sampling increments of 5.08 cm in length were analyzed for elemental concentrations with X-ray fluorescence (XRF), sediment pH, sediment oxidation-reduction potential (ORP), total volatile organic carbon (TVOC) concentration in the sample headspace, and abundant bacteria (16S rRNA sequencing). Over the core's length, gradients observed ranged from 3.74 to 8.03 for sediment pH, -141.4 mV to +651.0 mV for sediment ORP, and from below detection to a maximum of 9.6 ppm TVOC concentration (as chlorobenzene) in the headspace. The Fe and S gradients correlated with the presence of Fe and S reducing bacteria. S concentrations peaked in the Upper Zone and Zone 1 where Desulfosporosinus was abundant, suggesting precipitation of iron sulfide minerals. In Zone 2, Fe concentrations decreased where Geobacter was abundant, potentially resulting in Fe reduction, dissolution, and precipitation of minerals with increased solubility compared to the Fe(III) minerals. Using complementary geochemical and microbial data, five redox transition zones were delineated in the core collected. This research demonstrates a systematic approach to characterizing redox transition zones in a contaminated environment.

Application of hardwood biochar as a reactive capping mat to stabilize mercury derived from contaminated floodplain soil and riverbank sediments.

Hardwood biochar (pyrolyzed at 700 °C), a potential candidate for Hg removal, has been proposed for use as reactive capping mats along groundwater discharge zones or riverbanks to control release of Hg from contaminated riverbank sediments. Frequent flooding and drainage in fluvial settings can influence the effectiveness of remediation systems in contaminated riverbank sediments and floodplain soils. This study evaluated the effectiveness of Hg removal using hardwood biochar under hydrogeochemical conditions representative of those present within a reactive capping mat installed in a fluvial setting. Two sets of treatment columns, containing 50% v.v biochar and quartz sand, were subjected to 100 weekly wetting/drying cycles that included dry air, water-saturated air, and drainage using leachate derived from two source columns as input solutions: 1. Passing simulated acid rain water through floodplain soil, 2. Passing river water through riverbank sediment. In both treatment columns, >80% of the Hg was retained on the biochar without promoting Hg methylation and the release of other unintended dissolved constituents (including N, P, DOC). Results from solidphase extraction analyses suggest that Hg accumulated near the air/biochar-sand interface (0-2 cm) in the treatment columns at low loadings but was present at greater depths at higher loadings. Results of micro X-ray fluorescence (µ-XRF) mapping and micro X-ray absorption near edge structure (µ-XANES) for the biochar collected at depths 0-2 cm in treatment columns suggest retention of Hg-bearing particles derived from riverbank sediment and floodplain soil within the pore structure of the biochar. Sulfur K-edge XANES analysis of the unused biochar and the biochar after treatment suggest formation of Hg complexes on the biochar surface. These results indicate that hardwood biochar is potentially an effective media for application in reactive mats for controlling Hg discharging from contaminated riverbank sediments.

Evaluation of mercury stabilization mechanisms by sulfurized biochars determined using X-ray absorption spectroscopy.

The application of biochar to treat mercury (Hg) in the environment is being proposed on an increasing basis due to its widespread availability and cost effectiveness. However, the efficiency of Hg removal by biochars is variable due to differences in source material composition. In this study, a series of batch tests were conducted to evaluate the effectiveness of sulfurized biochars (calcium polysulfide and a dimercapto-related compound, respectively) for Hg removal; Hg-loaded biochars were then characterized using synchrotron-based techniques. Concentrations of Hg decreased by >99.5% in solutions containing the sulfurized biochars. Sulfur X-ray absorption near-edge structure (XANES) analyses indicate a polysulfur-like structure in polysulfide-sulfurized biochar and a thiol-like structure (shifted compared to dimercapto) in the dimercapto-sulfurized biochar. Micro-X-ray fluorescence (µ-XRF) mapping and confocal X-ray micro-fluorescence imaging (CXMFI) analyses indicate Hg is distributed primarily on the edges of sulfurized biochar and throughout unmodified biochar particles. Hg extended X-ray absorption fine structure (EXAFS) analyses show Hg in enriched areas is bound to chlorine (Cl) in the unmodified biochar and to S in sulfurized biochars. These results indicate that Hg removal efficiency is enhanced after sulfurization through the formation of strong bonds (Hg-S) with S-functional groups in the sulfurized biochars.

Isotopic Characterization of Mercury Downstream of Historic Industrial Contamination in the South River, Virginia.

Historic point source mercury (Hg) contamination from industrial processes on the South River (Waynesboro, Virginia) ended decades ago, but elevated Hg concentrations persist in the river system. In an effort to better understand Hg sources, mobility, and transport in the South River, we analyzed total Hg (THg) concentrations and Hg stable isotope compositions of streambed sediments, stream bank soils, suspended particles, and filtered surface waters. Samples were collected along a longitudinal transect of the South River, starting upstream of the historic Hg contamination point-source and extending downstream to the confluence with the South Fork Shenandoah River. Analysis of the THg concentration and Hg isotopic composition of these environmental samples indicates that the regional background Hg source is isotopically distinct in both Δ199Hg and δ202Hg from Hg derived from the original source of contamination, allowing the tracing of contamination-sourced Hg throughout the study reach. Three distinct end-members are required to explain the Hg isotopic and concentration variation observed in the South River. A consistent negative offset in δ202Hg values (∼0.28‰) was observed between Hg in the suspended particulate and dissolved phases, and this fractionation provides insight into the processes governing partitioning and transport of Hg in this contaminated river system.

Sediment Monitored Natural Recovery Evidenced by Compound Specific Isotope Analysis and High-Resolution Pore Water Sampling.

Monitoring natural recovery of contaminated sediments requires the use of techniques that can provide definitive evidence of in situ contaminant degradation. In this study, a passive diffusion sampler, called "peeper", was combined with Compound Specific Isotope Analysis to determine benzene and monochlorobenzene (MCB) stable carbon isotope values at a fine vertical resolution (3 cm) across the sediment water interface at a contaminated site. Results indicated significant decrease in concentrations of MCB from the bottom to the top layers of the sediment over 25 cm, and a 3.5 ‰ enrichment in δ13C values of MCB over that distance. Benzene was always at lower concentrations than MCB, with consistently more depleted δ13C values than MCB. The redox conditions were dominated by iron reduction along most of the sediment profile. These results provide multiple lines of evidence for in situ reductive dechlorination of MCB to benzene. Stable isotope analysis of contaminants in pore water is a valuable method to demonstrate in situ natural recovery of contaminated sediments. This novel high-resolution approach is critical to deciphering the combined effects of parent contaminant (e.g., MCB) degradation and both production and simultaneous degradation of daughter products, especially benzene.

Mechanisms of mercury removal by biochars produced from different feedstocks determined using X-ray absorption spectroscopy.

Thirty-six biochars produced from distinct feedstocks at different temperatures were evaluated for their potential to remove mercury (Hg) from aqueous solution at environmentally relevant concentrations. Concentrations of total Hg (THg) decreased by >90% in batch systems containing biochars produced at 600 and 700 °C and by 40-90% for biochars produced at 300 °C. Elevated concentrations of SO4(2-) (up to 1000 mg L(-1)) were observed in solutions mixed with manure-based biochars. Sulfur X-ray absorption near edge structure (XANES) analyses indicate the presence of both reduced and oxidized S species in both unwashed and washed biochars. Sulfur XANES spectra obtained from biochars with adsorbed Hg were similar to those of washed biochars. Micro-X-ray fluorescence mapping results indicate that Hg was heterogeneously distributed across biochar particles. Extended X-ray absorption fine structure modeling indicates Hg was bound to S in biochars with high S content and to O and Cl in biochars with low S content. The predominant mechanisms of Hg removal are likely the formation of chemical bonds between Hg and various functional groups on the biochar. This investigation provides information on the effectiveness and mechanisms of Hg removal that is critical for evaluating biochar applications for stabilization of Hg in surface water, groundwater, soils, and sediments.

Ecological Effects of Biochar on the Structure and Function of Stream Benthic Communities.

The introduction of biochar, activated carbon, and other carbonaceous materials to aquatic ecosystems significantly reduces the toxicity and bioavailability of contaminants. However, previous studies have shown that these materials can have negative effects on aquatic organisms. We conducted field and mesocosm experiments to test the hypothesis that biochar altered the structure and function of stream benthic communities. After 30 d in the field, colonization by stoneflies (Plecoptera) was significantly lower in trays containing biochar compared to the results from the controls. In stream mesocosms, biochar increased macroinvertebrate drift and significantly reduced community metabolism. However, most measures of community composition showed little variation among biochar treatments, and significant responses were limited to a single stonefly species (Capnia confusa). When benthic communities were simultaneously exposed to biochar and Cu, effects were primarily associated with metal exposure. Because it is unlikely that biochar treatments would be employed in uncontaminated areas, these moderately negative effects should be considered within the context of the positive benefits associated with reduced contaminant bioavailability and toxicity. Additional research is necessary to improve our understanding of the mechanisms responsible for biochar effects on benthic communities and to identify the optimal application rates and size fractions that will maximize contaminant sorption but minimize potential negative effects.

Aqueous leaching of organic acids and dissolved organic carbon from various biochars prepared at different temperatures.

Biochar has been used as a soil amendment, as a water treatment material, and for carbon (C) sequestration. Thirty-six biochars, produced from wood, agricultural residue, and manure feedstocks at different temperatures, were evaluated for the aqueous leaching of different forms of soluble C. The release of inorganic C (alkalinity), organic acids (OAs), and total dissolved organic C (DOC) was highly variable and dependent on the feedstock and pyrolysis temperature. The pH and alkalinity increased for the majority of samples. Higher pH values were associated with high-temperature (high-T) (600 and 700°C) biochars. Statistically significant differences in alkalinity were not observed between low-temperature (low-T) (300°C) and high-T biochars, whereas alkalinity released from wood-based biochar was significantly lower than from others. Concentrations of OAs and DOC released from low-T biochars were greater than from high-T biochars. The C in the OAs represented 1 to 60% of the total DOC released, indicating the presence of other DOC forms. The C released as DOC represented up to 3% (majority <0.1%) of the total C in the biochar. Scanning electron microscopy with energy dispersive X-ray spectroscopy showed the high-T biochars had a greater proportion of micropores. Fourier transform infrared spectroscopy showed that hydroxyl, aliphatic, and quinone were the predominant functional groups of all biochars and that the abundance of other functional groups was dependent on the feedstock. The release of DOC, especially bioavailable forms such as OAs, may promote growth of organisms and heavy metal complexation and diminish the potential effectiveness of various biochars for C sequestration.

Diffusion sampler for compound specific carbon isotope analysis of dissolved hydrocarbon contaminants.

Compound Specific Isotope Analysis (CSIA) is widely utilized to study the fate of organic contaminants in groundwater. To date, however, no method is available to obtain CSIA samples at a fine (cm) spatial scale across the sediment-surface water interface (SWI), a key boundary for discharge of contaminated groundwater to surface water. Dissolved contaminants in such discharged zones undergo rapid temporal and spatial changes due to heterogeneity in redox conditions and microbial populations. The compatibility of a passive sediment pore water sampler ("peeper") to collect 40 mL samples for CSIA of benzene, toluene, monochlorobenzene, and 1,2-dichlorobenzene at field-relevant concentrations (0.1-5 mg L(-1)) was evaluated in laboratory experiments. Results demonstrate that physical diffusion across the polysulfone membrane does not alter the carbon isotope values (±0.5‰). Measured δ(13)C values also remain invariant despite significant adsorption of the compounds on the peeper material, an effect which increased with higher numbers of chlorine atoms and sorption coefficient (Koc) values. In addition, isotope equilibrium between the peeper chamber and the sediment pore water occurred in less than a day, indicating the peeper method can be used to provide samples for CSIA analysis at fine spatial and temporal sampling resolutions in contaminated sediments.

Laboratory and pilot-scale bioremediation of pentaerythritol tetranitrate (PETN) contaminated soil.

PETN (pentaerythritol tetranitrate), a munitions constituent, is commonly encountered in munitions-contaminated soils, and pose a serious threat to aquatic organisms. This study investigated anaerobic remediation of PETN-contaminated soil at a site near Denver Colorado. Both granular iron and organic carbon amendments were used in both laboratory and pilot-scale tests. The laboratory results showed that, with various organic carbon amendments, PETN at initial concentrations of between 4500 and 5000mg/kg was effectively removed within 84 days. In the field trial, after a test period of 446 days, PETN mass removal of up to 53,071mg/kg of PETN (80%) was achieved with an organic carbon amendment (DARAMEND) of 4% by weight. In previous laboratory studies, granular iron has shown to be highly effective in degrading PETN. However, for both the laboratory and pilot-scale tests, granular iron was proven to be ineffective. This was a consequence of passivation of the iron surfaces caused by the very high concentrations of nitrate in the contaminated soil. This study indicated that low concentration of organic carbon was a key factor limiting bioremediation of PETN in the contaminated soil. Furthermore, the addition of organic carbon amendments such as the DARAMEND materials or brewers grain, proved to be highly effective in stimulating the biodegradation of PETN and could provide the basis for full-scale remediation of PETN-contaminated sites.

Activated carbon mitigates mercury and methylmercury bioavailability in contaminated sediments.

There are few available in situ remediation options for Hg contaminated sediments, short of capping. Here we present the first tests of activated carbon and other sorbents as potential in situ amendments for remediation of mercury and methylmercury (MeHg), using a study design that combined 2 L sediment/water microcosms with 14 day bioaccumulation assays. Our key end points were pore water concentrations, and bioaccumulation of total Hg and MeHg by a deposit-feeding oligochaete Lumbriculus variegatus. Four amendments were tested: an activated carbon (AC); CETCO Organoclay MRM (MRM); Thiol-SAMMS (TS), a thiol-functionalized mesoporous silica; and AMBERSEP GT74, an ion-exchange resin. Amendments were tested in four separate microcosm assays using Hg-contaminated sediments from two freshwater and two estuarine sites. AC and TS amendments, added at 2-7% of the dry weight of sediments significantly reduced both MeHg concentrations in pore waters, relative to unamended controls (by 45-95%) and bioaccumulation of MeHg by Lumbriculus (by between 30 and 90%). Both amendments had only small impacts on microcosm surface water, sediment and pore water chemistry, with the exception of significant reductions in pore water dissolved organic matter. The effectiveness of amendments in reducing bioaccumulation was well-correlated with their effectiveness in increasing sediment:water partitioning, especially of MeHg. Sediments with low native sediment:water MeHg partition coefficients were most effectively treated. Thus, in situ sediment sorbent amendments may be able to reduce the risk of biotic Hg and MeHg uptake in contaminated sediments, and subsequent contamination of food webs.

Development and validation of GFR-estimating equations using diabetes, transplant and weight.

BACKGROUND: We have reported a new equation (CKD-EPI equation) that reduces bias and improves accuracy for GFR estimation compared to the MDRD study equation while using the same four basic predictor variables: creatinine, age, sex and race. Here, we describe the development and validation of this equation as well as other equations that incorporate diabetes, transplant and weight as additional predictor variables. METHODS: Linear regression was used to relate log-measured GFR (mGFR) to sex, race, diabetes, transplant, weight, various transformations of creatinine and age with and without interactions. Equations were developed in a pooled database of 10 studies [2/3 (N = 5504) for development and 1/3 (N = 2750) for internal validation], and final model selection occurred in 16 additional studies [external validation (N = 3896)]. RESULTS: The mean mGFR was 68, 67 and 68 ml/min/ 1.73 m(2) in the development, internal validation and external validation datasets, respectively. In external validation, an equation that included a linear age term and spline terms in creatinine to account for a reduction in the magnitude of the slope at low serum creatinine values exhibited the best performance (bias = 2.5, RMSE = 0.250) among models using the four basic predictor variables. Addition of terms for diabetes and transplant did not improve performance. Equations with weight showed a small improvement in the subgroup with BMI <20 kg/m(2). CONCLUSIONS: The CKD-EPI equation, based on creatinine, age, sex and race, has been validated and is more accurate than the MDRD study equation. The addition of weight, diabetes and transplant does not significantly improve equation performance.

A comparison of change in measured and estimated glomerular filtration rate in patients with nondiabetic kidney disease.

BACKGROUND AND OBJECTIVES: All glomerular filtration rate (GFR) estimating equations have been developed from cross-sectional data. The aims of this study were to examine the concordance between use of measured GFR (mGFR) and estimated GFR (eGFR) in tracking changes in kidney function over time among patients with moderately severe chronic kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective cohort study of subjects who had been enrolled in the MDRD Study A and who had two or more contemporaneous assessments of mGFR and eGFR (n = 542; mGFR range, 25 to 55 ml/min per 1.73 m(2)) during the chronic phase (month 4 and afterwards). mGFR was based on urinary iothalamate clearance; eGFR was based on the 4-variable MDRD Study equation. Temporal changes in GFR were assessed by within-subject linear regression of time on GFR. RESULTS: Median follow-up time for all subjects was 2.6 yr; median number of GFR measurements was six. The eGFR slope tended to underestimate measured decrements in GFR. The absolute value of the difference in mGFR and eGFR slopes was

A modified logistic model to describe gadolinium kinetics in breast tumors.

A five-parameter modified logistic equation is presented that describes the signal enhancement in magnetic resonance dynamic contrast enhanced imaging (MRI-DCE). In this heuristic model, P(1) approximates the baseline signal, P(2) is related to the magnitude of the peak signal enhancement, P(3) is the approximate time of the maximum rate of increase of signal, P(4) is related to the maximum rate of signal enhancement, and P(5) is the terminal slope of the signal enhancement curve. Six breast tumors were studied that exhibited diverse patterns of signal enhancement, and in each case, estimated model parameters were well identified. Three of the model parameters, P(2), P(4) and P(5) describe attributes of the signal enhancement curve that have previously been shown to have diagnostic value with respect to breast cancer. Procedures for using the primary model parameters to derive a number of secondary parameters that may also have diagnostic value are discussed. Sensitivity analysis shows that the signal enhancement curve is highly sensitive to P(3) in the region of the signal intensity curve associated with rapid uptake of the contrast reagent. Consequently, frequent signal sampling in this time domain is indicated to enable identification of P(3) and sensitive fitting of the signal intensity curve. The advantages of this heuristic model compared to commonly used compartmental modeling approaches are discussed.