Seven suggestions for successful SGLT2i use in glomerular disease - a standalone CKD therapy?

PURPOSE OF REVIEW: Recent advances in the world of glomerular diseases have largely focussed on remission induction with immune modulating therapy. It is well recognised that even with the best available treatments, patients with glomerular diseases may have an increased risk of progressive renal and cardiovascular disease. RECENT FINDINGS: The arrival of large trials looking at the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with chronic kidney disease (CKD) and diabetes or not has shifted the entire focus of current management and the shift needs to go further. This review summarises the background to these landmark trials and provides practical guidance for implementation of the results in a general nephrology clinic. In sub-group analyses of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) clinical trial, SGLT2i improved renal outcomes in patients with immunoglobulin A (IgA) nephropathy highlighting the potential for this drug class in glomerular disease. We also discuss where the gaps in evidence are and where future trials in glomerular diseases, be they primary or secondary, should be focussed. SUMMARY: The renal community has never before had evidence of this strength upon which to base recommendations for patients with CKD and we should be grasping it with both hands.

Will advances in functional renal magnetic resonance imaging translate to the nephrology clinic?

Characterizing structural and tissue abnormalities of the kidney is fundamental to understanding kidney disease. Functional multi-parametric renal magnetic resonance imaging (MRI) is a noninvasive imaging strategy whereby several sequences are employed within a single session to quantify renal perfusion, tissue oxygenation, fibrosis, inflammation, and oedema without using ionizing radiation. In this review, we discuss evidence surrounding its use in several clinical settings including acute kidney injury, chronic kidney disease, hypertension, polycystic kidney disease and around renal transplantation. Kidney size on MRI is already a validated measure for making therapeutic decisions in the setting of polycystic kidney disease. Functional MRI sequences, T1 mapping and apparent diffusion coefficient, can non-invasively quantify interstitial fibrosis and so may have a near-future role in the nephrology clinic to stratify the risk of progressive chronic kidney disease or transplant dysfunction. Beyond this, multi-parametric MRI may be used diagnostically, for example differentiating inflammatory versus ischaemic causes of renal dysfunction, but this remains to be proven. Changes in MRI properties of kidney parenchyma may be useful surrogate markers to use as end points in clinical trials to assess if drugs prevent renal fibrosis or alter kidney perfusion. Large, multi-centre studies of functional renal MRI are ongoing which aim to provide definitive answers as to its role in the management of patients with renal dysfunction.

The ViKTORIES trial: A randomized, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients.

Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10-3  mmHg-1 ; p = .377), vascular calcification (treatment effect -141 [95% CI - 320 to 38] units; p = .124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach.

Myocardial changes on 3T cardiovascular magnetic resonance imaging in response to haemodialysis with fluid removal.

BACKGROUND: Mapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping. METHODS: This is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2. RESULTS: Twenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (- 25 ml, p = 0.002), LV stroke volume (- 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (- 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters. CONCLUSIONS: Acute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.

Prolonged SARS-CoV-2 viral shedding in patients with chronic kidney disease.

Recent World Health Organization guidance has aimed to provide pragmatic guidance acknowledging the role of sequential nasopharyngeal swabs taken >24 hours apart for SARS-CoV-2 in high-risk populations. Patients with chronic kidney disease (CKD) are known to have an altered immune milieu which may be associated with a delay in viral clearance. Here, a cross-sectional observational study of 138 patients admitted with SARS-CoV-2 infection at two large regional hospitals in Scotland, UK examined the median time to two consecutive negative nasopharyngeal swabs for SARS-CoV-2 in an inpatient population. The median time from admission to the first of two consecutive negative nasopharyngeal swabs was 18 days (range = 1-44) in patients with CKD, compared with 11 days (range: 1-71) in patients without CKD (P = .0007). Multivariable linear regression analysis using explanatory variables of age, sex, SARS-CoV-2 disease severity, key comorbidities and renal function showed that declining estimated glomerular filtration rate was independently associated with prolonged time to viral clearance. Our data suggest that patients with CKD who are admitted to hospital with SARS-CoV-2 take longer to achieve sequential negative nasopharyngeal swab reverse transcription-polymerase chain reaction results than those without CKD. This has implications for renal service provision, discharge planning and hospital capacity as well as a direct impact on patients due to extended hospital stay, anxiety and stigmatisation.

Comparing the interobserver reproducibility of different regions of interest on multi-parametric renal magnetic resonance imaging in healthy volunteers, patients with heart failure and renal transplant recipients.

OBJECTIVE: To assess interobserver reproducibility of different regions of interest (ROIs) on multi-parametric renal MRI using commercially available software. MATERIALS AND METHODS: Healthy volunteers (HV), patients with heart failure (HF) and renal transplant recipients (Tx) were recruited. Localiser scans, T1 mapping and pseudo-continuous arterial spin labelling (pCASL) were performed. HV and Tx also underwent diffusion-weighted imaging to allow calculation of apparent diffusion coefficient (ADC). For T1, pCASL and ADC, ROIs were drawn for whole kidney (WK), cortex (Cx), user-defined representative cortex (rep-Cx) and medulla. Intraclass correlation coefficient (ICC) and coefficient of variation (CoV) were assessed. RESULTS: Forty participants were included (10 HV, 10 HF and 20 Tx). The ICC for renal volume was 0.97 and CoV 6.5%. For T1 and ADC, WK, Cx, and rep-Cx were highly reproducible with ICC ≥ 0.76 and CoV < 5%. However, cortical pCASL results were more variable (ICC > 0.86, but CoV up to 14.2%). While reproducible, WK values were derived from a wide spread of data (ROI standard deviation 17% to 55% of the mean value for ADC and pCASL, respectively). Renal volume differed between groups (p < 0.001), while mean cortical T1 values were greater in Tx compared to HV (p = 0.009) and HF (p = 0.02). Medullary T1 values were also higher in Tx than HV (p = 0.03), while medullary pCASL values were significantly lower in Tx compared to HV and HF (p = 0.03 for both). DISCUSSION: Kidney volume calculated by manually contouring a localiser scan was highly reproducible between observers and detected significant differences across patient groups. For T1, pCASL and ADC, Cx and rep-Cx ROIs are generally reproducible with advantages over WK values.

Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI.

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.

Modeling temperature effects on a Coriolis mass flowmeter.

Coriolis mass flowmeters are used for many applications, including as transfer standards for proficiency testing and liquified natural gas (LNG) custody transfer. We developed a model to explain the temperature dependence of a Coriolis meter down to cryogenic temperatures. As a first step, we tested our model over the narrow temperature range of 285 K to 318 K in this work. The temperature dependence predicted by the model agrees with experimental data within ± 0.08 %; the model uncertainty is 0.16 % (95 % confidence level) over the temperature range of this work. Here, basic concepts of Coriolis flowmeters will be presented, and correction coefficients will be proposed that are valid down to 5 K based on literature values of material properties.

Interaction between socioeconomic deprivation and likelihood of pre-emptive transplantation: influence of competing risks and referral characteristics - a retrospective study.

Socioeconomic deprivation (SED) influences likelihood of pre-emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end-stage kidney disease (ESKD) and death. Of 7765 patients with follow-up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were "less deprived" with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation.

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases.

BACKGROUND: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). METHODS: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, > 25 to ≤30 kg/m2 and > 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. RESULTS: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1-66.2) years and BMI 28.2 (IQR 24.9-32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI > 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m2, 7.9% in BMI 25-30 kg/m2 and 10.7% in BMI > 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97-1.01, p = 0.31) nor blood pressure or GN diagnosis. CONCLUSION: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression.

Progress Towards a Gas-Flow Standard using Microwave and Acoustic Resonances.

We describe our progress in developing a novel gas flow standard that utilizes 1) microwave resonances to measure the volume, and 2) acoustic resonances to measure the average gas density of a collection tank / pressure vessel. The collection tank is a 1.85 m3, nearly-spherical, steel vessel used at pressures up to 7 MPa. Previously, using the cavity's microwave resonance frequencies, we determined the cavity's pressure- and temperature-dependent volume V BBB with the expanded uncertainty of 0.022 % (coverage factor k = 2, corresponding to 95 % confidence level). This was the first step in developing a pressure, volume, speed of sound, and time (PVwt) primary standard. In the present work, when the shell was filled with argon, measurements of pressure and acoustic resonance frequencies determined the "acoustic mass" M acst that agreed with gravimetric measurements within 0.04 %, even when temperature gradients were present. Most of these differences were a linear function of pressure; therefore, they can be reduced by further research. We designed and implemented a novel positive feedback system to measure the acoustic resonance frequencies. Using the measurements of V BBB, pressure, and acoustic resonance frequencies of the enclosed gas (nitrogen or argon), we calibrated 3 critical flow venturis that NIST has used as working standards for over 10 years. The two independent flow calibrations agreed within the long-term reproducibility of each CFV, which is less than 0.053 %. Furthermore, the feasibility of a dynamic tracking technique using this feedback loop was tested by comparing ΔM acst computed under no-flow conditions and ΔM acst computed by the rate of fall or rise during a flow. This was done for flows ranging from 0.11 g/s to 3.9 g/s.

Inter-study reproducibility of arterial spin labelling magnetic resonance imaging for measurement of renal perfusion in healthy volunteers at 3 Tesla.

BACKGROUND: Measurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers. METHODS: ASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning. RESULTS: 12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%. CONCLUSIONS: ASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.

Direct measurements of mass-specific optical cross sections of single-component aerosol mixtures.

The optical properties of atmospheric aerosols vary widely, being dependent upon particle composition, morphology, and mixing state. This diversity and complexity of aerosols motivates measurement techniques that can discriminate and quantify a variety of single- and multicomponent aerosols that are both internally and externally mixed. Here, we present a new combination of techniques to directly measure the mass-specific extinction and absorption cross sections of laboratory-generated aerosols that are relevant to atmospheric studies. Our approach employs a tandem differential mobility analyzer, an aerosol particle mass analyzer, cavity ring-down and photoacoustic spectrometers, and a condensation particle counter. This suite of instruments enables measurement of aerosol particle size, mass, extinction and absorption coefficients, and aerosol number density, respectively. Taken together, these observables yield the mass-specific extinction and absorption cross sections without the need to model particle morphology or account for sample collection artifacts. Here we demonstrate the technique in a set of case studies which involve complete separation of aerosol by charge, separation of an external mixture by mass, and discrimination between particle types by effective density and single-scattering albedo.

Dynamic measurement of gas flow using acoustic resonance tracking.

The National Institute of Standards and Technology measured gas flows exiting large, unthermostated, gas-filled, pressure vessels by tracking the time-dependent pressure P(t) and resonance frequency fN(t) of an acoustic mode N of the gas remaining in each vessel. This is a proof-of-principle demonstration of a gas flow standard that uses P(t), fN(t), and known values of the gas's speed of sound w(p,T) to determine a mode-weighted average temperature ⟨T⟩φ of the gas remaining in a pressure vessel while the vessel acts as a calibrated source of gas flow. To track fN(t) while flow work rapidly changed the gas's temperature, we sustained the gas's oscillations using positive feedback. Feedback oscillations tracked ⟨T⟩φ with a response time of order 1/fN. In contrast, driving the gas's oscillations with an external frequency generator yielded much slower response times of order Q/fN. (For our pressure vessels, Q ∼ 103-104, where Q is the ratio of the energy stored to the energy lost in one cycle of oscillation.) We tracked fN(t) of radial modes in a spherical vessel (1.85 m3) and of longitudinal modes of a cylindrical vessel (0.3 m3) during gas flows ranging from 0.24 to 12.4 g/s to determine the mass flows with an uncertainty of 0.51 % (95 % confidence level). We discuss the challenges in tracking fN(t) and ways to reduce the uncertainties.

Global longitudinal strain by feature-tracking cardiovascular magnetic resonance imaging predicts mortality in patients with end-stage kidney disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at increased risk of premature death, with cardiovascular disease being the predominant cause of death. We hypothesized that left ventricular global longitudinal strain (LV-GLS) measured by feature-tracking cardiovascular magnetic resonance imaging (CMRI) would be associated with all-cause mortality in patients with ESKD. METHODS: A pooled analysis of CMRI studies in patients with ESKD acquired within a single centre between 2002 and 2016 was carried out. CMR parameters including LV ejection fraction (LVEF), LV mass index, left atrial emptying fraction (LAEF) and LV-GLS were measured. We tested independent associations of CMR parameters with survival using a multivariable Cox model. RESULTS: Among 215 patients (mean age 54 years, 62% male), mortality was 53% over a median follow-up of 5 years. The median LVEF was 64.7% [interquartile range (IQR) 58.5-70.0] and the median LV-GLS was -15.3% (IQR -17.24 to -13.6). While 90% of patients had preserved LVEF (>50%), 58% of this group had abnormal LV-GLS (>-16%). On multivariable Cox regression, age {hazard ratio [HR] 1.04 [95% confidence interval (CI) 1.02-1.05]}, future renal transplant [HR 0.29 (95% CI 0.17-0.47)], LAEF [HR 0.98 (95% CI 0.96-1.00)] and LV-GLS [HR 1.08 (95% CI 1.01-1.16)] were independently associated with mortality. CONCLUSIONS: In this cohort of patients with ESKD, LV-GLS on feature-tracking CMRI and LAEF was associated with all-cause mortality, independent of baseline clinical variables and future renal transplantation. This effect was present even when >90% of the cohort had normal LVEF. Using LV-GLS instead of LVEF to diagnose cardiac dysfunction in patients with ESKD could result in a major advance in our understanding of cardiovascular disease in ESKD.

Photoacoustic spectrometer with a calculable cell constant for measurements of gases and aerosols.

We benchmark the performance of a photoacoustic spectrometer with a calculable cell constant in applications related to climate change measurements. As presently implemented, this spectrometer has a detection limit of 3.1 × 10(-9) W cm(-1) Hz(-1/2) for absorption by a gas and 1.5 × 10(-8) W cm(-1) Hz(-1/2) for soot particles. Nonstatistical uncertainty limited the accuracy of the instrument to ∼1%, and measurements of the concentration of CO(2) in laboratory air agreed with measurements made using a cavity ring-down spectrometer, to within 1%. Measurements of the enhanced absorption resulting from ultrathin (<5 nm), nonabsorbing coatings on nanoscale soot particles demonstrate the sensitivity of this instrument. Together, these measurements show the instrument's ability to quantitatively measure the absorption coefficient for species of interest to the climate and atmospheric science communities. Because the system constant is known, in most applications the acoustic response of this instrument need not be calibrated against a sample of known optical density, a decided advantage in field applications. Routine enhancements, such as improved processing of the photoacoustic signal and higher laser beam power, should further increase the instrument's precision and sensitivity.

Non-Contrast Renal Magnetic Resonance Imaging to Assess Perfusion and Corticomedullary Differentiation in Health and Chronic Kidney Disease.

AIMS: Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. METHODS: We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and xFB02;ow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. RESULTS: T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. CONCLUSIONS: Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD.

Cardiovascular complications after transplantation: treatment options in solid organ recipients.

Premature cardiovascular disease is the commonest cause of death in solid organ transplant recipients, with coronary artery disease, sudden cardiac death and heart failure being highly prevalent. There are unique factors leading to CV disease in organ transplant recipients that include underlying comorbidities, and metabolic effects of immunosuppression. As a consequence management strategies developed in the general population may have limited benefit. In this review, we will focus on renal transplantation, where most research has been carried out and, despite incomplete understanding of the disease process, the incidence of cardiovascular disease appears to be falling.

Theory of the Greenspan viscometer.

We present a detailed acoustic model of the Greenspan acoustic viscometer, a practical instrument for accurately measuring the viscosity eta of gases. As conceived by Greenspan, the viscometer is a Helmholtz resonator composed of two chambers coupled by a duct of radius rd. In the lowest order, eta=pi f rho(rd/Q)2, where f and Q are the frequency and quality factor of the isolated Greenspan mode, and rho is the gas density. In this level of approximation, the viscosity can be determined by measuring the duct radius and frequency response of the resonator. In the full acoustic model of the resonator, the duct is represented by a T-equivalent circuit, the chambers as lumped impedances, and the effects of the diverging fields at the duct ends by lumped end impedances with inertial and resistive components. The model accounts for contributions to 1/Q from thermal dissipation (primarily localized in the chambers) and from a capillary used for filling and evacuating the resonator. A robust, prototype instrument is being used for measuring the viscosity of reactive gases used in semiconductor processing. For well-characterized surrogate gases, the prototype viscometer generated values of eta that were within +/-0.8% of published reference values throughout the pressure range 0.2-3.2 MPa. Remarkably, we achieved this level of agreement by only slight adjustment of the numerically calculated inertial and resistive end effect parameters to improve the agreement with helium reference values. No other parameters were adjusted.